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Risk-Based Therapy in Treating Younger Patients With Newly Diagnosed Liver Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00980460
Recruitment Status : Active, not recruiting
First Posted : September 21, 2009
Results First Posted : December 28, 2021
Last Update Posted : June 28, 2022
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions PRETEXT Stage 1 Hepatoblastoma
PRETEXT Stage 2 Hepatoblastoma
PRETEXT Stage 3 Hepatoblastoma
PRETEXT Stage 4 Hepatoblastoma
Interventions Drug: Cisplatin
Drug: Dexrazoxane
Drug: Doxorubicin Hydrochloride
Drug: Fluorouracil
Drug: Irinotecan Hydrochloride
Other: Laboratory Biomarker Analysis
Procedure: Liver Transplantation
Drug: Temsirolimus
Procedure: Therapeutic Conventional Surgery
Drug: Vincristine Sulfate
Enrollment 236
Recruitment Details Study opened for enrollment on 09/14/2009 and closed on 07/20/2018
Pre-assignment Details  
Arm/Group Title Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Hide Arm/Group Description

Patients undergo surgery and then receive no further treatment.

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Period Title: Overall Study
Started 8 51 105 32 40
Completed 8 47 70 14 24
Not Completed 0 4 35 18 16
Reason Not Completed
Death             0             0             1             2             1
Lack of Efficacy             0             0             10             6             8
Lost to Follow-up             0             0             0             1             0
Physician Decision             0             0             11             5             3
Withdrawal by Subject             0             0             1             0             0
Ineligible             0             2             3             1             4
Refusal of further therapy             0             2             3             2             0
No therapy within 42 days of resection             0             0             3             1             0
No transplant by protocol timepoints             0             0             3             0             0
Arm/Group Title Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H) Total
Hide Arm/Group Description

Patients undergo surgery and then receive no further treatment.

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Total of all reporting groups
Overall Number of Baseline Participants 8 51 105 32 40 236
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
<=18 years
8
 100.0%
51
 100.0%
105
 100.0%
32
 100.0%
40
 100.0%
236
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
2.5  (2.56) 1.59  (1.71) 1.42  (2.61) 2.31  (2.4) 2.75  (2.9) 1.84  (2.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
Female
1
  12.5%
15
  29.4%
43
  41.0%
12
  37.5%
13
  32.5%
84
  35.6%
Male
7
  87.5%
36
  70.6%
62
  59.0%
20
  62.5%
27
  67.5%
152
  64.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
Hispanic or Latino
1
  12.5%
13
  25.5%
27
  25.7%
10
  31.3%
16
  40.0%
67
  28.4%
Not Hispanic or Latino
7
  87.5%
35
  68.6%
73
  69.5%
22
  68.8%
23
  57.5%
160
  67.8%
Unknown or Not Reported
0
   0.0%
3
   5.9%
5
   4.8%
0
   0.0%
1
   2.5%
9
   3.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  12.5%
5
   9.8%
8
   7.6%
2
   6.3%
6
  15.0%
22
   9.3%
Native Hawaiian or Other Pacific Islander
1
  12.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.4%
Black or African American
1
  12.5%
6
  11.8%
7
   6.7%
6
  18.8%
3
   7.5%
23
   9.7%
White
5
  62.5%
29
  56.9%
75
  71.4%
20
  62.5%
25
  62.5%
154
  65.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
11
  21.6%
15
  14.3%
4
  12.5%
6
  15.0%
36
  15.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 8 participants 51 participants 105 participants 32 participants 40 participants 236 participants
United States 8 50 98 30 37 223
Canada 0 1 4 2 0 7
Australia 0 0 3 0 0 3
Japan 0 0 0 0 3 3
1.Primary Outcome
Title Event-free Survival
Hide Description Estimated 5-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact.
Time Frame Time from patient enrollment to progression, treatment failure, death from any cause, diagnosis of a second malignant neoplasm, or last follow-up, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Only eligible patients are considered in the calculation of this outcome measure.
Arm/Group Title Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Hide Arm/Group Description:

Patients undergo surgery and then receive no further treatment.

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 8 49 102 31 36
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent Probability
100
(100 to 100)
87.21
(73.67 to 94.06)
87.03
(78.71 to 92.26)
43.61
(25.79 to 60.16)
46.38
(29.47 to 61.68)
2.Primary Outcome
Title Number of Cycles on Which Grade 3 or Higher Adverse Events Coded According to CTC AE Version 5 Were Observed
Hide Description All grade 3 or 4 or greater non-hematological toxicities. The frequency of each toxicity type will be quantified as the number of reporting periods on which the toxicity of the relevant grade is reported. This measure does not apply to patients enrolled in the VERY LOW RISK group.
Time Frame During protocol therapy up to 1 year after enrollment
Hide Outcome Measure Data
Hide Analysis Population Description
All eligible patients except for patients in the very low-risk group. Regimen T includes 49 cycles, Regimen F includes 269 cycles, Regimen W includes 107 cycles and Regimen H includes 124 cycles.
Arm/Group Title Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Hide Arm/Group Description:

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 51 105 32 40
Overall Number of Units Analyzed
Type of Units Analyzed: Cycles
49 269 107 124
Measure Type: Number
Unit of Measure: Cycles
Hearing impaired 1 20 4 4
Diarrhea 4 15 15 15
Enterocolitis 1 0 0 1
Nausea 1 10 10 3
Small intestinal obstruction 1 1 0 0
Vomiting 2 24 13 5
Abdominal distension 0 1 3 0
Abdominal pain 0 10 9 6
Colitis 0 3 1 1
Anal mucositis 0 1 0 0
Ascites 0 1 0 0
Malabsorption 0 1 0 0
Mucositis oral 0 44 8 6
Constipation 0 2 1 0
Dental caries 0 1 0 0
Typhlitis 0 2 2 1
Duodenal obstruction 0 1 0 0
Esophageal hemorrhage 0 1 0 0
Gastritis 0 1 1 0
Illeus 0 3 4 0
Oral pain 0 4 1 0
Small intestinal mucositis 0 1 0 0
Colonic hemorrhage 0 0 1 0
Dysphagia 0 0 1 0
Esophagitis 0 0 1 0
Gastroparesis 0 0 1 0
Gastric fistula 0 0 0 1
Gastrointestinal disorders - Other, specify 0 0 0 1
Obstruction gastric 0 0 0 1
Rectal mucositis 0 0 0 1
Fever 1 9 1 9
General disorders and administration site conditions - Other, specify 0 1 0 0
Pain 0 6 1 4
Multi-organ failure 0 1 0 2
Irritability 0 0 0 1
Infusion related reaction 0 0 0 1
Hypothermia 0 0 0 1
Catheter related infection 1 8 1 0
Infections and infestations - Other, specify 4 38 27 9
Mucosal infection 1 0 1 0
Otitis media 1 0 1 0
Urinary tract infection 1 3 0 3
Biliary tract infection 0 1 0 0
Abdominal infection 0 1 0 0
Bladder infection 0 2 0 0
Enterocolitis infectious 0 8 4 5
Duodenal infection 0 1 0 0
Upper respiratory infection 0 4 2 2
Eye infection 0 1 0 0
Wound infection 0 1 0 0
Sepsis 0 5 0 3
Lung infection 0 2 0 1
Peritoneal infection 0 1 0 0
Skin infection 0 1 1 7
Small intestine infection 0 1 0 0
Periorbital infection 0 0 0 1
Alanine aminotransferase increased 1 28 9 6
Aspartate aminotransferase increased 1 37 10 19
Activated partial thromboplastin time prolonged 0 2 3 1
Alkaline phosphatase increased 0 1 0 1
Blood bilirubin increased 0 7 2 5
Creatinine increased 0 3 0 1
GGT increased 0 7 1 6
Weight loss 0 6 4 6
Fibronogen decreased 0 2 0 1
Ejection fraction decreased 0 1 0 1
Investigations - Other, specify 0 1 0 0
White blood cell decreased 0 0 1 0
INR increased 0 0 1 0
CPK increased 0 0 0 1
Cholesterol high 0 0 0 1
Electrocardiogram QT corrected interval prolonged 0 0 0 1
Lipase increased 0 0 0 1
Serum amylase increased 0 0 0 1
Anorexia 1 30 20 17
Dehydration 3 13 3 12
Hyperglycemia 2 15 5 10
Hyperkalemia 2 12 3 5
Hypermagnesemia 2 4 0 0
Hypernatremia 2 1 0 3
Hypokalemia 4 48 12 29
Hyponatremia 1 22 6 10
Acidosis 0 4 0 1
Alkalosis 0 1 0 3
Hypocalcemia 0 7 4 2
Hypoalbuminemia 0 3 3 1
Hypomagnesemia 0 11 3 2
Hypophosphatemia 0 21 7 19
Tumor lysis syndrome 0 2 0 0
Hypercalcemia 0 0 1 0
Hypoglycemia 0 0 1 1
Hypertriglyceridemia 0 0 0 4
Metabolism and nutrition disorders - Other, specify 0 0 0 1
Peripheral sensory neuropathy 2 5 2 1
Oculomotor nerve disorder 0 3 0 0
Abducens nerve disorder 0 1 2 0
Peripheral motor neuropathy 0 7 3 2
Syncope 0 1 0 0
Dysphasia 0 0 1 0
Depressed level of consciousness 0 0 0 1
Seizure 0 0 0 1
Apnea 1 0 0 0
Atelectasis 0 2 0 0
Dyspnea 0 2 1 3
Bronchospasm 0 1 0 0
Hypoxia 0 10 2 6
Pleural effusion 0 2 2 1
Pulmonary edema 0 1 0 0
Stridor 0 1 0 0
Respiratory failure 0 2 0 1
Epistaxis 0 0 2 1
Wheezing 0 0 0 1
Hypertension 3 6 2 4
Hematoma 0 1 1 0
Hypotension 0 3 3 5
Vascular disorders - Other, specify 0 2 1 0
Thromboembolic event 0 0 1 1
Left ventricular systolic dysfunction 0 1 1 0
Cardiac arrest 0 1 3 0
Right ventricular dysfunction 0 2 0 0
Ventricular tachycardia 0 1 0 0
Cardiac disorders - Other, specify 0 0 1 0
Sinus tachycardia 0 0 1 4
Heart failure 0 0 1 1
Myocardial infarction 0 0 1 0
Biliary fistula 0 1 0 0
Hepatobiliary disorders - Other, specify 0 1 0 1
Hepatic hemorrhage 0 2 1 1
Portal vein thrombosis 0 1 0 0
Portal hypertension 0 0 1 0
Biliary anastomotic leak 0 1 1 0
Postoperative hemorrhage 0 1 1 0
Gastrointestinal anastomotic leak 0 0 2 0
Intraoperative hemorrhage 0 0 0 1
Arthralgia 0 1 0 0
Generalized muscle weakness 0 2 0 0
Back pain 0 1 0 0
Bone pain 0 1 0 0
Muscle weakness lower limb 0 1 0 0
Agitation 0 4 1 0
Hallucinations 0 1 0 0
Insomnia 0 0 0 1
Acute kidney injury 0 9 0 0
Renal and urinary disorders - Other, specify 0 3 1 0
Renal calculi 0 1 0 0
Proteinuria 0 0 0 1
Erythema multiforme 0 1 0 0
Skin and subcutaneous tissue disorders - Other, specify 0 2 0 1
Rash maculo-papular 0 3 1 2
Eye disorders - Other, specify 0 1 0 0
Surgical and medical procedures - Other, specify 0 1 0 0
Tumor pain 0 0 1 0
Allergic reaction 0 0 0 2
Anaphylaxis 0 0 0 2
Immune system disorders - Other, specify 0 0 0 1
3.Primary Outcome
Title Number of Deaths
Hide Description Number of patients who experience on-protocol-therapy death possibly, probably or likely related to systemic chemotherapy. This outcome measure applies to INTERMEDIATE RISK patients only.
Time Frame During protocol therapy or within 30 days of the termination of protocol therapy up to 1 year after enrollment
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Only eligible patients are considered in the calculation of this outcome measure.
Arm/Group Title Intermediate-risk Group (Regimen F)
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Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 102
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.0%
4.Primary Outcome
Title Disease Status at the End of 2 Courses of Therapy
Hide Description RECIST v 1.1 and serum alphafetoprotein responses are evaluated separately. RECIST v 1.1 complete response (CR) is defined as disappearance of all target lesions and partial response (PR) is defined as reduction of at last 30% in the sum of the longest dimension of all target lesions (CR and PR measured by CT or MRI) between enrollment. Serum alphafetoprotein response is a decrease of at least 90% from the last serum alphafetoprotein measurement from the baseline prior to the start of chemotherapy to the end of cycle 2. This is calculated for HIGH RISK regimen W and HIGH RISK regimen H only.
Time Frame First two cycles of therapy- up to 42 days after enrollment
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Thirty-two (32) patients were enrolled to Regiment W. Two were excluded from the analysis: (1)one was ineligible; and (2) one did not have an accurate report of initial AFP. Forty (40) patients were enrolled to Regiment H. Five were excluded from the analysis: (1)four were ineligible; and (2) one did not receive Temsirolimus.
Arm/Group Title High-risk Group (Regimen W) High-risk Group (Regimen H)
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(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 30 35
Measure Type: Number
Unit of Measure: participants
RECIST PR, no AFP response 3 3
AFP response, no RECIST response 5 10
RECIST response, AFP response 6 4
no AFP response, no RECIST response 16 18
5.Secondary Outcome
Title Feasibility of Referral for Liver Transplantation
Hide Description A patient for whom referral is considered appropriate who receives a consultation after enrollment will be considered a success with respect to feasibility.
Time Frame 3 cycles of therapy - up to 3 months after enrollment
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Only eligible patients with COG surgical stage III or IV disease and whose tumor is PRETEXT classified as PRETEXT 3-4 extensive multifocal; PRETEXT 3 +V; PRETEXT 3 +P; or PRETEXT 4 extensive multifocal are evaluated for feasibility of transplant referral.
Arm/Group Title Intermediate-risk Group (Regimen F) High-risk Group (Regimen H)
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Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Overall Number of Participants Analyzed 57 31
Measure Type: Count of Participants
Unit of Measure: Participants
37
  64.9%
16
  51.6%
Time Frame AEs and OAEs: Up to 6 months post-treatment planned as 18 months; All-Cause Mortality: up to 10 years
Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
 
Arm/Group Title Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
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Patients undergo surgery and then receive no further treatment.

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Patients undergo surgery and then receive adjuvant cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, and vincristine sulfate IV over 1 minute on days 2, 9, and 16. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive C5VD chemotherapy comprising cisplatin IV over 6 hours on day 1, fluorouracil IV over 2-4 minutes on day 2, vincristine sulfate IV over 1 minute on days 2, 9, and 16, and doxorubicin hydrochloride IV over 15 minutes on days 1-2. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo surgical resection after course 2 OR surgical resection or liver transplantation after course 4 of C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6. (Closed to accrual as of 3/12/2012)

Cisplatin: Given IV

Dexrazoxane: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

(regimen W replaced by regimen H as of Amendment 3B) Patients receive up front VI chemotherapy comprising vincristine sulfate IV on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5. Treatment with VI repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 1 courses of VI in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

Patients receive up front VIT chemotherapy comprising vincristine sulfate IV over 1 minute on days 1 and 8 and irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8. Treatment with VIT repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with disease response then receive 6 courses of C5VD with 4 courses of VIT in between each 2-course block. Patients with no disease response receive 6 courses of C5VD in the absence of disease progression or unacceptable toxicity. Patients undergo tumor resection or liver transplant after course 4 of C5VD followed by 2 courses of adjuvant C5VD. Patients may also receive dexrazoxane IV over 5-15 minutes on days 1-2 of courses 5 and 6.

Cisplatin: Given IV

Doxorubicin Hydrochloride: Given IV

Fluorouracil: Given IV

Irinotecan Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Liver Transplantation: Undergo liver transplant

Temsirolimus: Given IV

Therapeutic Conventional Surgery: Undergo surgery

Vincristine Sulfate: Given IV

All-Cause Mortality
Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   3/49 (6.12%)   7/102 (6.86%)   11/31 (35.48%)   13/36 (36.11%) 
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Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/49 (0.00%)   3/102 (2.94%)   2/31 (6.45%)   1/36 (2.78%) 
Blood and lymphatic system disorders           
Anemia   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Disseminated intravascular coagulation   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Febrile neutropenia   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Cardiac disorders           
Cardiac arrest   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Cardiac disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Heart failure   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Left ventricular systolic dysfunction   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Myocardial infarction   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Right ventricular dysfunction   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders           
Abdominal pain   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Ascites   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Esophageal hemorrhage   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Typhlitis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
General disorders           
Multi-organ failure   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Hepatobiliary disorders           
Portal hypertension   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Portal vein thrombosis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Infections and infestations           
Sepsis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Injury, poisoning and procedural complications           
Postoperative hemorrhage   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Renal and urinary disorders           
Acute kidney injury   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Hypoxia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Pulmonary edema   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Respiratory failure   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Vascular disorders           
Hypotension   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Thromboembolic event   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Very Low-risk Group Low-risk Group (Regimen T) Intermediate-risk Group (Regimen F) High-risk Group (Regimen W) High-risk Group (Regimen H)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   24/49 (48.98%)   91/102 (89.22%)   27/31 (87.10%)   32/36 (88.89%) 
Blood and lymphatic system disorders           
Anemia   0/8 (0.00%)  1/49 (2.04%)  2/102 (1.96%)  0/31 (0.00%)  1/36 (2.78%) 
Disseminated intravascular coagulation   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Febrile neutropenia   0/8 (0.00%)  7/49 (14.29%)  50/102 (49.02%)  19/31 (61.29%)  14/36 (38.89%) 
Cardiac disorders           
Cardiac arrest   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  0/36 (0.00%) 
Heart failure   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Left ventricular systolic dysfunction   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Right ventricular dysfunction   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Sinus tachycardia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  2/36 (5.56%) 
Ventricular tachycardia   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Ear and labyrinth disorders           
Hearing impaired   0/8 (0.00%)  1/49 (2.04%)  18/102 (17.65%)  2/31 (6.45%)  4/36 (11.11%) 
Eye disorders           
Eye disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders           
Abdominal distension   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  0/36 (0.00%) 
Abdominal pain   0/8 (0.00%)  0/49 (0.00%)  7/102 (6.86%)  3/31 (9.68%)  5/36 (13.89%) 
Anal mucositis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Colitis   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  0/31 (0.00%)  1/36 (2.78%) 
Colonic hemorrhage   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Constipation   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  1/31 (3.23%)  0/36 (0.00%) 
Dental caries   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Diarrhea   0/8 (0.00%)  4/49 (8.16%)  12/102 (11.76%)  8/31 (25.81%)  13/36 (36.11%) 
Duodenal obstruction   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Enterocolitis   0/8 (0.00%)  1/49 (2.04%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Gastric fistula   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Gastritis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Gastrointestinal disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Gastroparesis   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Ileus   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  1/31 (3.23%)  1/36 (2.78%) 
Malabsorption   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Mucositis oral   0/8 (0.00%)  0/49 (0.00%)  30/102 (29.41%)  5/31 (16.13%)  6/36 (16.67%) 
Nausea   0/8 (0.00%)  1/49 (2.04%)  8/102 (7.84%)  4/31 (12.90%)  3/36 (8.33%) 
Obstruction gastric   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Oral pain   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  1/31 (3.23%)  0/36 (0.00%) 
Rectal mucositis   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Small intestinal mucositis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Small intestinal obstruction   0/8 (0.00%)  1/49 (2.04%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Typhlitis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  2/31 (6.45%)  1/36 (2.78%) 
Vomiting   0/8 (0.00%)  2/49 (4.08%)  19/102 (18.63%)  9/31 (29.03%)  4/36 (11.11%) 
General disorders           
Fever   0/8 (0.00%)  1/49 (2.04%)  8/102 (7.84%)  0/31 (0.00%)  11/36 (30.56%) 
General disorders and administration site conditions - Other, specify   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Hypothermia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Infusion related reaction   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Irritability   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Multi-organ failure   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  1/36 (2.78%) 
Pain   0/8 (0.00%)  0/49 (0.00%)  6/102 (5.88%)  1/31 (3.23%)  2/36 (5.56%) 
Hepatobiliary disorders           
Biliary fistula   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Hepatic hemorrhage   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  1/36 (2.78%) 
Hepatobiliary disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  1/36 (2.78%) 
Immune system disorders           
Allergic reaction   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  2/36 (5.56%) 
Anaphylaxis   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  2/36 (5.56%) 
Immune system disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Infections and infestations           
Abdominal infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Biliary tract infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Bladder infection   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Catheter related infection   0/8 (0.00%)  1/49 (2.04%)  5/102 (4.90%)  1/31 (3.23%)  0/36 (0.00%) 
Duodenal infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Enterocolitis infectious   0/8 (0.00%)  0/49 (0.00%)  6/102 (5.88%)  2/31 (6.45%)  4/36 (11.11%) 
Eye infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Infections and infestations - Other, specify   0/8 (0.00%)  4/49 (8.16%)  26/102 (25.49%)  16/31 (51.61%)  7/36 (19.44%) 
Lung infection   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  1/36 (2.78%) 
Mucosal infection   0/8 (0.00%)  1/49 (2.04%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Otitis media   0/8 (0.00%)  1/49 (2.04%)  0/102 (0.00%)  0/31 (0.00%)  0/36 (0.00%) 
Periorbital infection   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Peritoneal infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Sepsis   0/8 (0.00%)  0/49 (0.00%)  4/102 (3.92%)  0/31 (0.00%)  3/36 (8.33%) 
Skin infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  5/36 (13.89%) 
Small intestine infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Upper respiratory infection   0/8 (0.00%)  0/49 (0.00%)  4/102 (3.92%)  2/31 (6.45%)  2/36 (5.56%) 
Urinary tract infection   0/8 (0.00%)  1/49 (2.04%)  2/102 (1.96%)  0/31 (0.00%)  3/36 (8.33%) 
Wound infection   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Injury, poisoning and procedural complications           
Biliary anastomotic leak   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  0/36 (0.00%) 
Gastrointestinal anastomotic leak   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Intraoperative hemorrhage   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Postoperative hemorrhage   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Investigations           
Activated partial thromboplastin time prolonged   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  3/31 (9.68%)  1/36 (2.78%) 
Alanine aminotransferase increased   0/8 (0.00%)  1/49 (2.04%)  21/102 (20.59%)  7/31 (22.58%)  6/36 (16.67%) 
Alkaline phosphatase increased   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  1/36 (2.78%) 
Aspartate aminotransferase increased   0/8 (0.00%)  1/49 (2.04%)  26/102 (25.49%)  7/31 (22.58%)  16/36 (44.44%) 
Blood bilirubin increased   0/8 (0.00%)  0/49 (0.00%)  7/102 (6.86%)  2/31 (6.45%)  5/36 (13.89%) 
Cholesterol high   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
CPK increased   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Creatinine increased   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  0/31 (0.00%)  1/36 (2.78%) 
Ejection fraction decreased   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  1/36 (2.78%) 
Electrocardiogram QT corrected interval prolonged   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  2/36 (5.56%) 
Fibrinogen decreased   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  1/36 (2.78%) 
GGT increased   0/8 (0.00%)  0/49 (0.00%)  6/102 (5.88%)  1/31 (3.23%)  5/36 (13.89%) 
INR increased   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Investigations - Other, specify   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Lipase increased   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Neutrophil count decreased   0/8 (0.00%)  3/49 (6.12%)  4/102 (3.92%)  1/31 (3.23%)  0/36 (0.00%) 
Platelet count decreased   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Serum amylase increased   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Weight loss   0/8 (0.00%)  0/49 (0.00%)  4/102 (3.92%)  3/31 (9.68%)  6/36 (16.67%) 
White blood cell decreased   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Metabolism and nutrition disorders           
Acidosis   0/8 (0.00%)  0/49 (0.00%)  4/102 (3.92%)  0/31 (0.00%)  1/36 (2.78%) 
Alkalosis   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  2/36 (5.56%) 
Anorexia   0/8 (0.00%)  1/49 (2.04%)  19/102 (18.63%)  9/31 (29.03%)  11/36 (30.56%) 
Dehydration   0/8 (0.00%)  3/49 (6.12%)  8/102 (7.84%)  2/31 (6.45%)  10/36 (27.78%) 
Hypercalcemia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Hyperglycemia   0/8 (0.00%)  2/49 (4.08%)  14/102 (13.73%)  2/31 (6.45%)  7/36 (19.44%) 
Hyperkalemia   0/8 (0.00%)  2/49 (4.08%)  9/102 (8.82%)  3/31 (9.68%)  4/36 (11.11%) 
Hypermagnesemia   0/8 (0.00%)  2/49 (4.08%)  4/102 (3.92%)  0/31 (0.00%)  0/36 (0.00%) 
Hypernatremia   0/8 (0.00%)  2/49 (4.08%)  1/102 (0.98%)  0/31 (0.00%)  2/36 (5.56%) 
Hypertriglyceridemia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  4/36 (11.11%) 
Hypoalbuminemia   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  2/31 (6.45%)  1/36 (2.78%) 
Hypocalcemia   0/8 (0.00%)  0/49 (0.00%)  7/102 (6.86%)  4/31 (12.90%)  2/36 (5.56%) 
Hypoglycemia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  1/36 (2.78%) 
Hypokalemia   0/8 (0.00%)  4/49 (8.16%)  37/102 (36.27%)  7/31 (22.58%)  16/36 (44.44%) 
Hypomagnesemia   0/8 (0.00%)  0/49 (0.00%)  11/102 (10.78%)  3/31 (9.68%)  2/36 (5.56%) 
Hyponatremia   0/8 (0.00%)  1/49 (2.04%)  15/102 (14.71%)  4/31 (12.90%)  9/36 (25.00%) 
Hypophosphatemia   0/8 (0.00%)  0/49 (0.00%)  18/102 (17.65%)  6/31 (19.35%)  13/36 (36.11%) 
Metabolism and nutrition disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Tumor lysis syndrome   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Back pain   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Bone pain   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Generalized muscle weakness   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Muscle weakness lower limb   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Tumor pain   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Nervous system disorders           
Abducens nerve disorder   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Depressed level of consciousness   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Dysphasia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  1/31 (3.23%)  0/36 (0.00%) 
Oculomotor nerve disorder   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Peripheral motor neuropathy   0/8 (0.00%)  0/49 (0.00%)  4/102 (3.92%)  2/31 (6.45%)  2/36 (5.56%) 
Peripheral sensory neuropathy   0/8 (0.00%)  2/49 (4.08%)  4/102 (3.92%)  1/31 (3.23%)  1/36 (2.78%) 
Seizure   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Syncope   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Psychiatric disorders           
Agitation   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  1/31 (3.23%)  0/36 (0.00%) 
Hallucinations   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Insomnia   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Renal and urinary disorders           
Acute kidney injury   0/8 (0.00%)  0/49 (0.00%)  5/102 (4.90%)  0/31 (0.00%)  0/36 (0.00%) 
Proteinuria   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Renal and urinary disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  0/31 (0.00%)  0/36 (0.00%) 
Renal calculi   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Apnea   0/8 (0.00%)  1/49 (2.04%)  0/102 (0.00%)  0/31 (0.00%)  0/36 (0.00%) 
Atelectasis   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  0/36 (0.00%) 
Bronchospasm   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Cough   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Dyspnea   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  3/36 (8.33%) 
Epistaxis   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  2/31 (6.45%)  1/36 (2.78%) 
Hypoxia   0/8 (0.00%)  0/49 (0.00%)  7/102 (6.86%)  1/31 (3.23%)  6/36 (16.67%) 
Pleural effusion   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  2/31 (6.45%)  1/36 (2.78%) 
Respiratory failure   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Stridor   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Wheezing   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Skin and subcutaneous tissue disorders           
Erythema multiforme   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Rash maculo-papular   0/8 (0.00%)  0/49 (0.00%)  3/102 (2.94%)  0/31 (0.00%)  2/36 (5.56%) 
Skin and subcutaneous tissue disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  0/31 (0.00%)  1/36 (2.78%) 
Surgical and medical procedures           
Surgical and medical procedures - Other, specify   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  0/31 (0.00%)  0/36 (0.00%) 
Vascular disorders           
Hematoma   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  1/31 (3.23%)  0/36 (0.00%) 
Hypertension   0/8 (0.00%)  3/49 (6.12%)  4/102 (3.92%)  2/31 (6.45%)  4/36 (11.11%) 
Hypotension   0/8 (0.00%)  0/49 (0.00%)  1/102 (0.98%)  2/31 (6.45%)  4/36 (11.11%) 
Thromboembolic event   0/8 (0.00%)  0/49 (0.00%)  0/102 (0.00%)  0/31 (0.00%)  1/36 (2.78%) 
Vascular disorders - Other, specify   0/8 (0.00%)  0/49 (0.00%)  2/102 (1.96%)  1/31 (3.23%)  0/36 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 626-447-0064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00980460    
Obsolete Identifiers: NCT02265692
Other Study ID Numbers: NCI-2011-01975
NCI-2011-01975 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AHEP0731
10-00098
COG-AHEP0731
CDR0000654889
AHEP0731 ( Other Identifier: Children's Oncology Group )
AHEP0731 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
First Submitted: September 18, 2009
First Posted: September 21, 2009
Results First Submitted: August 4, 2021
Results First Posted: December 28, 2021
Last Update Posted: June 28, 2022