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FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric 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: NCT01747551
Recruitment Status : Completed
First Posted : December 11, 2012
Results First Posted : May 8, 2018
Last Update Posted : February 10, 2020
Sponsor:
Information provided by (Responsible Party):
Peter C. Enzinger, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Conditions Esophageal Cancer
Gastric Cancer
Interventions Drug: Oxaliplatin
Drug: Leucovorin
Drug: Fluorouracil
Drug: Ziv-aflibercept
Enrollment 64
Recruitment Details Patients enrolled from January 2013 through April 2015.
Pre-assignment Details  
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death. Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Period Title: Overall Study
Started 43 21
Completed 0 0
Not Completed 43 21
Reason Not Completed
Progressive Disease             24             17
Death             3             1
Adverse Event             7             1
Prolonged Treatment Delay             2             0
Withdrawal by Subject             3             1
Physician Decision             2             1
Other             2             0
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo Total
Hide Arm/Group Description Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death. Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death. Total of all reporting groups
Overall Number of Baseline Participants 43 21 64
Hide Baseline Analysis Population Description
The analysis dataset is comprised of all randomized patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 43 participants 21 participants 64 participants
62
(32 to 83)
62
(40 to 79)
62
(21 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 21 participants 64 participants
Female
6
  14.0%
3
  14.3%
9
  14.1%
Male
37
  86.0%
18
  85.7%
55
  85.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 21 participants 64 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   4.8%
1
   1.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   4.8%
1
   1.6%
White
41
  95.3%
18
  85.7%
59
  92.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   4.7%
1
   4.8%
3
   4.7%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 43 participants 21 participants 64 participants
43
 100.0%
21
 100.0%
64
 100.0%
1.Primary Outcome
Title 6-month Progression-free Survival (PFS)
Hide Description 6-month PFS is the percent probability of patients remaining alive and progression-free at 6-months from randomization estimated using Kaplan-Meier methods. PFS was measured as the time from randomization to 1st documented disease progression (PD) or death. Patients alive without PD were censored at the earliest of the date of last progression-free disease assessment or start of non-protocol therapy. Per RECIST 1.1 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Time Frame Tumor assessments were performed every 8 weeks and evaluated by independent, blinded radiologists. Patient follow-up was 6 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all randomized patients.
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description:
Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed 43 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability
60.5
(44.3 to 73.3)
57.1
(33.8 to 74.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mFOLFOX6 + Ziv-aflibercept, mFOLFOX6 + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.72
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Grade 4 Treatment-Related Toxicity Rate
Hide Description The percentage of patients who experienced maximum grade 4 treatment-related adverse event based on CTCAEv4 as reported on case report forms.
Time Frame Adverse events were collected each cycle on treatment. Patients received a median (range) treatment duration (months) of 6.9 (0-23.3) and 6.4 (0-43.9) for mFOLFOX6/ziv-aflibercept and mFOLFOX6/placebo, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description:
Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed 43 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
11.6
(3.9 to 25.1)
9.5
(1.2 to 30.4)
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description ORR was defined as the percentage of patients achieving complete response (CR) or partial response (PR) on treatment based on RECIST 1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time Frame Tumor assessments were performed every 8 weeks and evaluated by independent, blinded radiologists. Patients received a median (range) treatment duration (m) of 6.9 (0-23.3) and 6.4 (0-43.9) for mFOLFOX6/ziv-aflibercept and mFOLFOX6/placebo, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all patients with measurable disease at baseline.
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description:
Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed 36 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
61.1
(43.5 to 76.9)
75.0
(47.6 to 97.2)
4.Secondary Outcome
Title Duration of Objective Response
Hide Description Duration of response is the time from date of first documented confirmed objective response to date of first documented progressive disease. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum LD, taking as reference the smallest sum on study with at least 5 mm absolute increase. For non-target lesions, progression-free means no new lesions or unequivocal progression on existing non-target lesions or not evaluated.
Time Frame Tumor assessments were performed every 8 weeks and evaluated by independent, blinded radiologists. Patient follow-up (months) median (range) was 14.5 (1.1-49.8) and 18.8 (0.6-49.8) for mFOLFOX6/ziv-aflibercept and mFOLFOX6/placebo, respectively.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of patients who achieved objective response except one patient on the mFOLFOX6+Placebo is missing data.
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description:
Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Overall Number of Participants Analyzed 22 11
Mean (Full Range)
Unit of Measure: months
9.0
(1.4 to 22.0)
8.0
(1.8 to 16.8)
Time Frame Adverse events were assessed day 1 of each cycle. Patients received a median (range) treatment duration (months) of 6.9 (0-23.3) and 6.4 (0-43.9) for mFOLFOX6/ziv-aflibercept and mFOLFOX6/placebo, respectively.
Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. All remaining events regardless of treatment attribution were classified as Other AEs. Per the source vocabulary (CTCAEv4.0) there is a category "Other, specify" for each system organ class. No further data is available to specify classification beyond this general term.
 
Arm/Group Title mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Hide Arm/Group Description Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death. Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
All-Cause Mortality
mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   2/43 (4.65%)   0/21 (0.00%) 
Hide Serious Adverse Events
mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   34/43 (79.07%)   9/21 (42.86%) 
Blood and lymphatic system disorders     
Anemia  1  1/43 (2.33%)  0/21 (0.00%) 
Febrile neutropenia  1  0/43 (0.00%)  1/21 (4.76%) 
Cardiac disorders     
Cardiac disorders -Other  1  1/43 (2.33%)  0/21 (0.00%) 
Heart failure  1  1/43 (2.33%)  0/21 (0.00%) 
Myocardial infarction  1  1/43 (2.33%)  0/21 (0.00%) 
Ear and labyrinth disorders     
Middle ear inflammation  1  0/43 (0.00%)  1/21 (4.76%) 
Gastrointestinal disorders     
Abdominal pain  1  1/43 (2.33%)  0/21 (0.00%) 
Constipation  1  1/43 (2.33%)  0/21 (0.00%) 
Dysphagia  1  0/43 (0.00%)  1/21 (4.76%) 
Gastric hemorrhage  1  1/43 (2.33%)  0/21 (0.00%) 
Gastrointestinal disorders -Other  1  2/43 (4.65%)  0/21 (0.00%) 
Mucositis oral  1  3/43 (6.98%)  0/21 (0.00%) 
Nausea  1  1/43 (2.33%)  0/21 (0.00%) 
Upper gastrointestinal hemorrhage  1  1/43 (2.33%)  1/21 (4.76%) 
Vomiting  1  0/43 (0.00%)  1/21 (4.76%) 
General disorders     
Fatigue  1  3/43 (6.98%)  1/21 (4.76%) 
Malaise  1  1/43 (2.33%)  0/21 (0.00%) 
Infections and infestations     
Infections and infestations -Other  1  0/43 (0.00%)  1/21 (4.76%) 
Sepsis  1  1/43 (2.33%)  0/21 (0.00%) 
Investigations     
Investigations -Other  1  0/43 (0.00%)  1/21 (4.76%) 
Neutrophil count decreased  1  12/43 (27.91%)  4/21 (19.05%) 
White blood cell decreased  1  1/43 (2.33%)  1/21 (4.76%) 
Metabolism and nutrition disorders     
Anorexia  1  3/43 (6.98%)  0/21 (0.00%) 
Dehydration  1  1/43 (2.33%)  0/21 (0.00%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorder - Other  1  1/43 (2.33%)  0/21 (0.00%) 
Nervous system disorders     
Intracranial hemorrhage  1  1/43 (2.33%)  0/21 (0.00%) 
Peripheral sensory neuropathy  1  3/43 (6.98%)  2/21 (9.52%) 
Syncope  1  0/43 (0.00%)  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis  1  1/43 (2.33%)  0/21 (0.00%) 
Hiccups  1  1/43 (2.33%)  0/21 (0.00%) 
Hoarseness  1  2/43 (4.65%)  0/21 (0.00%) 
Respiratory, thoracic and mediastinal disorders -Other  1  1/43 (2.33%)  0/21 (0.00%) 
Vascular disorders     
Hypertension  1  21/43 (48.84%)  1/21 (4.76%) 
Hypotension  1  0/43 (0.00%)  1/21 (4.76%) 
Superior vena cava syndrome  1  0/43 (0.00%)  1/21 (4.76%) 
Thromboembolic event  1  4/43 (9.30%)  0/21 (0.00%) 
Vascular disorders -Other  1  1/43 (2.33%)  0/21 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
mFOLFOX6 + Ziv-aflibercept mFOLFOX6 + Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   43/43 (100.00%)   21/21 (100.00%) 
Blood and lymphatic system disorders     
Anemia  1  32/43 (74.42%)  13/21 (61.90%) 
Blood and lymphatic system disorders - Other  1  3/43 (6.98%)  0/21 (0.00%) 
Febrile neutropenia  1  2/43 (4.65%)  1/21 (4.76%) 
Leukocytosis  1  4/43 (9.30%)  2/21 (9.52%) 
Thrombotic thrombocytopenic purpura  1  1/43 (2.33%)  0/21 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  0/43 (0.00%)  1/21 (4.76%) 
Cardiac disorders - Other  1  1/43 (2.33%)  0/21 (0.00%) 
Chest pain - cardiac  1  2/43 (4.65%)  0/21 (0.00%) 
Heart failure  1  1/43 (2.33%)  0/21 (0.00%) 
Sinus bradycardia  1  0/43 (0.00%)  1/21 (4.76%) 
Sinus tachycardia  1  2/43 (4.65%)  1/21 (4.76%) 
Ventricular tachycardia  1  1/43 (2.33%)  0/21 (0.00%) 
Eye disorders     
Blurred vision  1  1/43 (2.33%)  2/21 (9.52%) 
Dry eye  1  2/43 (4.65%)  0/21 (0.00%) 
Eye disorders - Other  1  1/43 (2.33%)  0/21 (0.00%) 
Photophobia  1  1/43 (2.33%)  0/21 (0.00%) 
Watering eyes  1  2/43 (4.65%)  0/21 (0.00%) 
Watering eyes  1  0/43 (0.00%)  1/21 (4.76%) 
Gastrointestinal disorders     
Abdominal distension  1  1/43 (2.33%)  2/21 (9.52%) 
Abdominal pain  1  20/43 (46.51%)  9/21 (42.86%) 
Anal pain  1  1/43 (2.33%)  0/21 (0.00%) 
Bloating  1  4/43 (9.30%)  1/21 (4.76%) 
Colitis  1  0/43 (0.00%)  1/21 (4.76%) 
Constipation  1  26/43 (60.47%)  13/21 (61.90%) 
Diarrhea  1  25/43 (58.14%)  9/21 (42.86%) 
Dry mouth  1  4/43 (9.30%)  0/21 (0.00%) 
Dyspepsia  1  1/43 (2.33%)  1/21 (4.76%) 
Dysphagia  1  19/43 (44.19%)  9/21 (42.86%) 
Esophageal pain  1  1/43 (2.33%)  0/21 (0.00%) 
Fecal incontinence  1  1/43 (2.33%)  0/21 (0.00%) 
Flatulence  1  0/43 (0.00%)  2/21 (9.52%) 
Gastritis  1  0/43 (0.00%)  1/21 (4.76%) 
Gastroesophageal reflux disease  1  5/43 (11.63%)  3/21 (14.29%) 
Gastrointestinal disorders - Other  1  13/43 (30.23%)  10/21 (47.62%) 
Gastrointestinal pain  1  9/43 (20.93%)  2/21 (9.52%) 
Hemorrhoids  1  4/43 (9.30%)  0/21 (0.00%) 
Lip pain  1  1/43 (2.33%)  0/21 (0.00%) 
Mucositis oral  1  20/43 (46.51%)  6/21 (28.57%) 
Nausea  1  32/43 (74.42%)  15/21 (71.43%) 
Oral dysesthesia  1  8/43 (18.60%)  1/21 (4.76%) 
Oral hemorrhage  1  1/43 (2.33%)  1/21 (4.76%) 
Oral pain  1  9/43 (20.93%)  0/21 (0.00%) 
Rectal hemorrhage  1  1/43 (2.33%)  0/21 (0.00%) 
Rectal pain  1  2/43 (4.65%)  0/21 (0.00%) 
Rectal perforation  1  0/43 (0.00%)  1/21 (4.76%) 
Stomach pain  1  1/43 (2.33%)  0/21 (0.00%) 
Vomiting  1  10/43 (23.26%)  0/21 (0.00%) 
Vomiting  1  0/43 (0.00%)  5/21 (23.81%) 
General disorders     
Chills  1  2/43 (4.65%)  1/21 (4.76%) 
Death neonatal  1  1/43 (2.33%)  0/21 (0.00%) 
Edema limbs  1  0/43 (0.00%)  2/21 (9.52%) 
Facial pain  1  1/43 (2.33%)  1/21 (4.76%) 
Fatigue  1  37/43 (86.05%)  19/21 (90.48%) 
Fever  1  3/43 (6.98%)  3/21 (14.29%) 
Gait disturbance  1  0/43 (0.00%)  1/21 (4.76%) 
General disorders and administration site conditions - Other  1  0/43 (0.00%)  1/21 (4.76%) 
Infusion related reaction  1  3/43 (6.98%)  0/21 (0.00%) 
Injection site reaction  1  1/43 (2.33%)  0/21 (0.00%) 
Localized edema  1  3/43 (6.98%)  3/21 (14.29%) 
Malaise  1  9/43 (20.93%)  2/21 (9.52%) 
Non-cardiac chest pain  1  4/43 (9.30%)  2/21 (9.52%) 
Pain  1  11/43 (25.58%)  5/21 (23.81%) 
Hepatobiliary disorders     
Gallbladder pain  1  1/43 (2.33%)  0/21 (0.00%) 
Infections and infestations     
Infections and infestations - Other  1  0/43 (0.00%)  1/21 (4.76%) 
Paronychia  1  1/43 (2.33%)  0/21 (0.00%) 
Sinusitis  1  1/43 (2.33%)  0/21 (0.00%) 
Skin infection  1  0/43 (0.00%)  1/21 (4.76%) 
Tooth infection  1  1/43 (2.33%)  0/21 (0.00%) 
Upper respiratory infection  1  3/43 (6.98%)  1/21 (4.76%) 
Injury, poisoning and procedural complications     
Bruising  1  2/43 (4.65%)  2/21 (9.52%) 
Fracture  1  0/43 (0.00%)  1/21 (4.76%) 
Hip fracture  1  1/43 (2.33%)  0/21 (0.00%) 
Injury, poisoning and procedural complications - Other  1  1/43 (2.33%)  1/21 (4.76%) 
Intraoperative hepatobiliary injury  1  0/43 (0.00%)  1/21 (4.76%) 
Vascular access complication  1  1/43 (2.33%)  0/21 (0.00%) 
Wound dehiscence  1  2/43 (4.65%)  0/21 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  10/43 (23.26%)  4/21 (19.05%) 
Alkaline phosphatase increased  1  21/43 (48.84%)  10/21 (47.62%) 
Aspartate aminotransferase increased  1  19/43 (44.19%)  10/21 (47.62%) 
Blood bilirubin increased  1  3/43 (6.98%)  2/21 (9.52%) 
Cholesterol high  1  1/43 (2.33%)  0/21 (0.00%) 
Creatinine increased  1  4/43 (9.30%)  1/21 (4.76%) 
Haptoglobin decreased  1  1/43 (2.33%)  2/21 (9.52%) 
Hemoglobin increased  1  0/43 (0.00%)  1/21 (4.76%) 
INR increased  1  1/43 (2.33%)  0/21 (0.00%) 
Investigations - Other  1  7/43 (16.28%)  3/21 (14.29%) 
Lymphocyte count decreased  1  1/43 (2.33%)  0/21 (0.00%) 
Neutrophil count decreased  1  17/43 (39.53%)  7/21 (33.33%) 
Platelet count decreased  1  23/43 (53.49%)  13/21 (61.90%) 
Weight gain  1  1/43 (2.33%)  0/21 (0.00%) 
Weight loss  1  11/43 (25.58%)  4/21 (19.05%) 
White blood cell decreased  1  8/43 (18.60%)  3/21 (14.29%) 
Metabolism and nutrition disorders     
Alkalosis  1  1/43 (2.33%)  0/21 (0.00%) 
Anorexia  1  27/43 (62.79%)  8/21 (38.10%) 
Dehydration  1  6/43 (13.95%)  1/21 (4.76%) 
Glucose intolerance  1  0/43 (0.00%)  1/21 (4.76%) 
Hypercalcemia  1  1/43 (2.33%)  0/21 (0.00%) 
Hyperglycemia  1  35/43 (81.40%)  16/21 (76.19%) 
Hyperkalemia  1  2/43 (4.65%)  2/21 (9.52%) 
Hypermagnesemia  1  1/43 (2.33%)  1/21 (4.76%) 
Hypernatremia  1  2/43 (4.65%)  1/21 (4.76%) 
Hypoalbuminemia  1  31/43 (72.09%)  5/21 (23.81%) 
Hypocalcemia  1  6/43 (13.95%)  3/21 (14.29%) 
Hypoglycemia  1  4/43 (9.30%)  1/21 (4.76%) 
Hypokalemia  1  9/43 (20.93%)  2/21 (9.52%) 
Hypomagnesemia  1  5/43 (11.63%)  3/21 (14.29%) 
Hyponatremia  1  17/43 (39.53%)  7/21 (33.33%) 
Hypophosphatemia  1  2/43 (4.65%)  0/21 (0.00%) 
Iron overload  1  1/43 (2.33%)  0/21 (0.00%) 
Metabolism and nutrition disorders - Other, specify  1  4/43 (9.30%)  4/21 (19.05%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/43 (6.98%)  0/21 (0.00%) 
Arthritis  1  1/43 (2.33%)  0/21 (0.00%) 
Back pain  1  6/43 (13.95%)  3/21 (14.29%) 
Flank pain  1  1/43 (2.33%)  0/21 (0.00%) 
Generalized muscle weakness  1  3/43 (6.98%)  2/21 (9.52%) 
Growth suppression  1  3/43 (6.98%)  0/21 (0.00%) 
Joint range of motion decreased cervical spine  1  1/43 (2.33%)  0/21 (0.00%) 
Musculoskeletal and connective tissue disorder - Other  1  4/43 (9.30%)  0/21 (0.00%) 
Neck pain  1  0/43 (0.00%)  1/21 (4.76%) 
Pain in extremity  1  5/43 (11.63%)  2/21 (9.52%) 
Nervous system disorders     
Dizziness  1  10/43 (23.26%)  4/21 (19.05%) 
Dysesthesia  1  27/43 (62.79%)  12/21 (57.14%) 
Dysgeusia  1  11/43 (25.58%)  6/21 (28.57%) 
Dysphasia  1  2/43 (4.65%)  0/21 (0.00%) 
Headache  1  13/43 (30.23%)  1/21 (4.76%) 
Movements involuntary  1  1/43 (2.33%)  0/21 (0.00%) 
Nervous system disorders - Other  1  2/43 (4.65%)  2/21 (9.52%) 
Paresthesia  1  1/43 (2.33%)  2/21 (9.52%) 
Peripheral motor neuropathy  1  0/43 (0.00%)  1/21 (4.76%) 
Peripheral sensory neuropathy  1  36/43 (83.72%)  16/21 (76.19%) 
Presyncope  1  0/43 (0.00%)  1/21 (4.76%) 
Sinus pain  1  1/43 (2.33%)  0/21 (0.00%) 
Tremor  1  0/43 (0.00%)  1/21 (4.76%) 
Psychiatric disorders     
Anxiety  1  4/43 (9.30%)  2/21 (9.52%) 
Confusion  1  1/43 (2.33%)  0/21 (0.00%) 
Depression  1  4/43 (9.30%)  1/21 (4.76%) 
Insomnia  1  11/43 (25.58%)  3/21 (14.29%) 
Renal and urinary disorders     
Acute kidney injury  1  1/43 (2.33%)  0/21 (0.00%) 
Proteinuria  1  8/43 (18.60%)  0/21 (0.00%) 
Renal and urinary disorders - Other  1  2/43 (4.65%)  1/21 (4.76%) 
Urinary retention  1  0/43 (0.00%)  1/21 (4.76%) 
Urinary tract pain  1  2/43 (4.65%)  0/21 (0.00%) 
Reproductive system and breast disorders     
Pelvic pain  1  1/43 (2.33%)  0/21 (0.00%) 
Reproductive system and breast disorders - Other, specify  1  2/43 (4.65%)  0/21 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  15/43 (34.88%)  3/21 (14.29%) 
Dyspnea  1  12/43 (27.91%)  3/21 (14.29%) 
Epistaxis  1  16/43 (37.21%)  2/21 (9.52%) 
Hiccups  1  3/43 (6.98%)  1/21 (4.76%) 
Hoarseness  1  13/43 (30.23%)  1/21 (4.76%) 
Hypoxia  1  1/43 (2.33%)  0/21 (0.00%) 
Nasal congestion  1  3/43 (6.98%)  0/21 (0.00%) 
Nasal congestion  1  0/43 (0.00%)  1/21 (4.76%) 
Pharyngeal necrosis  1  0/43 (0.00%)  1/21 (4.76%) 
Pneumonitis  1  0/43 (0.00%)  1/21 (4.76%) 
Postnasal drip  1  5/43 (11.63%)  0/21 (0.00%) 
Respiratory, thoracic and mediastinal disorders - Other  1  4/43 (9.30%)  0/21 (0.00%) 
Sinus disorder  1  1/43 (2.33%)  0/21 (0.00%) 
Sore throat  1  2/43 (4.65%)  1/21 (4.76%) 
Voice alteration  1  4/43 (9.30%)  0/21 (0.00%) 
Wheezing  1  0/43 (0.00%)  1/21 (4.76%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  1/43 (2.33%)  2/21 (9.52%) 
Dry skin  1  1/43 (2.33%)  1/21 (4.76%) 
Erythema multiforme  1  1/43 (2.33%)  0/21 (0.00%) 
Nail discoloration  1  2/43 (4.65%)  0/21 (0.00%) 
Nail ridging  1  1/43 (2.33%)  0/21 (0.00%) 
Palmar-plantar erythrodysesthesia syndrome  1  6/43 (13.95%)  2/21 (9.52%) 
Photosensitivity  1  0/43 (0.00%)  2/21 (9.52%) 
Rash acneiform  1  0/43 (0.00%)  1/21 (4.76%) 
Rash maculo-papular  1  1/43 (2.33%)  0/21 (0.00%) 
Skin and subcutaneous tissue disorders - Other  1  12/43 (27.91%)  4/21 (19.05%) 
Skin hyperpigmentation  1  3/43 (6.98%)  1/21 (4.76%) 
Skin ulceration  1  1/43 (2.33%)  0/21 (0.00%) 
Urticaria  1  0/43 (0.00%)  1/21 (4.76%) 
Vascular disorders     
Flushing  1  1/43 (2.33%)  1/21 (4.76%) 
Hematoma  1  0/43 (0.00%)  2/21 (9.52%) 
Hot flashes  1  1/43 (2.33%)  2/21 (9.52%) 
Hypertension  1  36/43 (83.72%)  12/21 (57.14%) 
Hypotension  1  3/43 (6.98%)  1/21 (4.76%) 
Thromboembolic event  1  1/43 (2.33%)  1/21 (4.76%) 
Vascular disorders - Other  1  2/43 (4.65%)  0/21 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Peter Enzinger
Organization: Dana-Farber Cancer Institute
Phone: 617-632-3029
Layout table for additonal information
Responsible Party: Peter C. Enzinger, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01747551    
Other Study ID Numbers: 12-401
First Submitted: December 5, 2012
First Posted: December 11, 2012
Results First Submitted: April 5, 2018
Results First Posted: May 8, 2018
Last Update Posted: February 10, 2020