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Trial record 7 of 17 for:    "Germ Cells Tumors" | "Thiotepa"

Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors

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ClinicalTrials.gov Identifier: NCT00047320
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : February 27, 2014
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Brain Tumor
Central Nervous System Tumors
Childhood Germ Cell Tumor
Interventions Drug: carboplatin
Drug: etoposide
Drug: ifosfamide
Drug: thiotepa
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Enrollment 104
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

radiation therapy: craniospinal irradiation

Period Title: Overall Study
Started 104
Completed 76
Not Completed 28
Reason Not Completed
Lack of Efficacy             8
Lost to Follow-up             1
Physician Decision             8
Withdrawal by Subject             9
Ineligible             2
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

radiation therapy: craniospinal irradiation

Overall Number of Baseline Participants 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 104 participants
12
(3 to 23)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants
Female
25
  24.0%
Male
79
  76.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants
American Indian or Alaska Native
1
   1.0%
Asian
8
   7.7%
Native Hawaiian or Other Pacific Islander
2
   1.9%
Black or African American
9
   8.7%
White
72
  69.2%
More than one race
0
   0.0%
Unknown or Not Reported
12
  11.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 104 participants
Hispanic or Latino
17
  16.3%
Not Hispanic or Latino
85
  81.7%
Unknown or Not Reported
2
   1.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 104 participants
United States 88
Canada 10
Australia 5
New Zealand 1
1.Primary Outcome
Title Response to Induction Chemotherapy
Hide Description A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 102 eligible patients, 85 completed induction chemotherapy with sufficient data to assess response. Central review response assessment is used.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 85
Measure Type: Count of Participants
Unit of Measure: Participants
Responder
74
  87.1%
Non-Responder
11
  12.9%
2.Secondary Outcome
Title The Probability of Event-free Survival (EFS)
Hide Description Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate.
Time Frame At 3 years from study entry
Hide Outcome Measure Data
Hide Analysis Population Description
Two ineligible patients were excluded. A total of 102 eligible patients were analyzed.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.837
(0.763 to 0.910)
3.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate.
Time Frame At 3 years from study entry
Hide Outcome Measure Data
Hide Analysis Population Description
Two ineligible patients were excluded. A total of 102 eligible patients were analyzed. one patient died without the disease progression reported. But the death was due to the disease. The death was counted as “event” when progression-free survival (PFS) was calculated. So EFS and PFS at 3 years were same.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.837
(0.763 to 0.910)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate.
Time Frame At 3 years from study entry
Hide Outcome Measure Data
Hide Analysis Population Description
Two ineligible patients were excluded. A total of 102 eligible patients were analyzed.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.927
(0.876 to 0.979)
5.Secondary Outcome
Title Number of Patients Experiencing Toxic Death
Hide Description Toxic death, defined as death predominantly attributable to treatment-related causes.
Time Frame During chemotherapy (up to 18 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 102 eligible patients treated with induction chemotherapy were included.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 102
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
6.Secondary Outcome
Title Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
Hide Description The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.
Time Frame During chemotherapy(up to 18 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 102 eligible patients treated with induction chemotherapy were included.
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description:

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

thiotepa: Given IV

adjuvant therapy

conventional surgery

neoadjuvant therapy

peripheral blood stem cell transplantation

radiation therapy: craniospinal irradiation

Overall Number of Participants Analyzed 102
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: participants
22
(14 to 31)
Time Frame [Not Specified]
Adverse Event Reporting Description 104 patients enrolled, 2 are ineligible and not included in adverse event reporting. Therefore, adverse events participants reported is 102.
 
Arm/Group Title Radiation Therapy (CR From Induction)
Hide Arm/Group Description

Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.

carboplatin: Given IV

etoposide: Given IV

ifosfamide: Given IV

radiation therapy: craniospinal irradiation

All-Cause Mortality
Radiation Therapy (CR From Induction)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Radiation Therapy (CR From Induction)
Affected / at Risk (%) # Events
Total   8/102 (7.84%)    
Blood and lymphatic system disorders   
Febrile neutropenia  1/102 (0.98%)  1
Gastrointestinal disorders   
Nausea  1/102 (0.98%)  1
Investigations   
Lymphocyte count decreased  1/102 (0.98%)  2
Neutrophil count decreased  3/102 (2.94%)  5
Platelet count decreased  1/102 (0.98%)  1
White blood cell decreased  1/102 (0.98%)  2
Metabolism and nutrition disorders   
Hyperkalemia  1/102 (0.98%)  1
Hypernatremia  1/102 (0.98%)  3
Hypokalemia  2/102 (1.96%)  3
Hypophosphatemia  1/102 (0.98%)  1
Nervous system disorders   
Headache  1/102 (0.98%)  1
Seizure  1/102 (0.98%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Radiation Therapy (CR From Induction)
Affected / at Risk (%) # Events
Total   70/102 (68.63%)    
Blood and lymphatic system disorders   
Anemia  51/102 (50.00%)  108
Febrile neutropenia  8/102 (7.84%)  9
Gastrointestinal disorders   
Nausea  8/102 (7.84%)  16
Vomiting  15/102 (14.71%)  28
Infections and infestations   
Infections and infestations - Other, specify  8/102 (7.84%)  10
Investigations   
Alanine aminotransferase increased  23/102 (22.55%)  39
Aspartate aminotransferase increased  15/102 (14.71%)  22
Lymphocyte count decreased  19/102 (18.63%)  42
Neutrophil count decreased  53/102 (51.96%)  104
Platelet count decreased  53/102 (51.96%)  96
White blood cell decreased  48/102 (47.06%)  114
Metabolism and nutrition disorders   
Hyperglycemia  18/102 (17.65%)  37
Hyperkalemia  8/102 (7.84%)  8
Hypermagnesemia  10/102 (9.80%)  11
Hypernatremia  20/102 (19.61%)  32
Hypoalbuminemia  6/102 (5.88%)  7
Hypocalcemia  15/102 (14.71%)  22
Hypokalemia  26/102 (25.49%)  39
Hypomagnesemia  9/102 (8.82%)  13
Hyponatremia  31/102 (30.39%)  57
Hypophosphatemia  8/102 (7.84%)  12
Nervous system disorders   
Headache  8/102 (7.84%)  8
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.
Must obtain prior Sponsor approval.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 352-273-0558
EMail: Resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00047320     History of Changes
Other Study ID Numbers: ACNS0122
CDR0000257664 ( Other Identifier: Clinical Trials.gov )
COG-ACNS0122 ( Other Identifier: Children's Oncology Group )
First Submitted: October 3, 2002
First Posted: January 27, 2003
Results First Submitted: January 15, 2014
Results First Posted: February 27, 2014
Last Update Posted: February 14, 2018