Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sorafenib in Treating Patients With Refractory Non-Small Cell Lung 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: NCT00064350
Recruitment Status : Completed
First Posted : July 9, 2003
Results First Posted : November 28, 2012
Last Update Posted : November 30, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Lung Cancer
Interventions Drug: Sorafenib
Drug: Placebo
Enrollment 342
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Induction Then Sorafenib Induction Then Placebo Then Sorafenib Induction, Not Randomized
Hide Arm/Group Description

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization.

Randomization: Patients with stable disease after the induction treatment were randomized to receive either sorafenib or placebo. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease.

In the study design, only patients on the placebo arm with progressive disease may cross over to receive sorafenib. Due to drug dispensing error, even though some patients actually received straight sorafenib during Step 2 (randomization) treatment, they were thought to be randomized onto the placebo arm upon progression and unblinding (before finding out the fact of the dispensing error). Consequently, these patients were crossed over to Step 3, and there were 10 of them.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.

Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients in this group did not enter Step 2 (randomization part) after the induction phase.

Period Title: Induction Treatment
Started 59 46 237
Treated 59 46 228
Eligible and Treated 59 46 194
Completed 51 37 1
Not Completed 8 9 236
Reason Not Completed
Disease Progression             5             1             110
Adverse Event             0             2             49
Death             0             0             9
Withdrawal by Subject             0             0             21
Ineligible or never started treatment             3             6             34
Other             0             0             13
Period Title: Randomization
Started 59 46 0
Treated 55 40 0
Eligible and Treated 50 31 0
Completed 33 28 0
Not Completed 26 18 0
Reason Not Completed
Adverse Event             8             3             0
Death             3             0             0
Withdrawal by Subject             1             0             0
Ineligible or never started treatment             9             15             0
Other             5             0             0
Period Title: Cross-Over
Started 10 27 0
Treated 9 26 0
Eligible and Treated 7 21 0
Completed 4 13 0
Not Completed 6 14 0
Reason Not Completed
Adverse Event             0             1             0
Death             1             3             0
Withdrawal by Subject             2             2             0
Ineligible or never started treatment             3             6             0
Other             0             2             0
Arm/Group Title Induction Then Sorafenib Induction Then Placebo Then Sorafenib Induction, Not Randomized Total
Hide Arm/Group Description

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization.

Randomization: Patients with stable disease after the induction treatment were randomized to receive either sorafenib or placebo. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease.

In the study design, only patients on the placebo arm with progressive disease may cross over to receive sorafenib. Due to drug dispensing error, even though some patients actually received straight sorafenib during Step 2 (randomization) treatment, they were thought to be randomized onto the placebo arm upon progression and unblinding (before finding out the fact of the dispensing error). Consequently, these patients were crossed over to Step 3, and there were 10 of them.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.

Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm.

To show baseline characteristics for eligible and treated patients in both the randomization phase (the most important part of this study) and the induction phase, this group contains the following patients:

  • eligible and treated patients who were not randomized (n=194)
  • randomized patients who were not eligible or did not start treatment in the randomization phase (n=24)

There were 218 patients in this group so the total number of patients is 299 and the entire cohort represents all eligible and treated patients in the induction phase.

Total of all reporting groups
Overall Number of Baseline Participants 50 31 218 299
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 50 participants 31 participants 218 participants 299 participants
64.5
(42 to 80)
69
(40 to 86)
63
(33 to 85)
64
(33 to 86)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 50 participants 31 participants 218 participants 299 participants
Female 27 13 90 130
Male 23 18 127 168
Unknown 0 0 1 1
1.Primary Outcome
Title Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
Hide Description

Per RECIST Criteria (V1.0):

Complete Response (CR): disappearance of all target lesions Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions Progressive Disease (PD): >=20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of longest diameter recorded since randomization, or the appearance of new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD

Time Frame Two months after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:
Patients initially received Sorafenib in Step 2 (randomization part)
Patients initially received placebo in Step 2 (randomization part)
Overall Number of Participants Analyzed 50 31
Measure Type: Number
Unit of Measure: participants
Response 0 0
Stable Disease 27 7
Progression 19 23
Unevaluable 4 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib, Placebo
Comments Compare the proportion of patients maintaining stable disease or objective response at 2 months after randomization between the two arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival is defined as the duration from randomization to disease progression or death, whichever occurs first. Only randomized patients were included in this analysis.
Time Frame Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:
Patients initially received Sorafenib in Step 2 (randomization part)
Patients initially received placebo in Step 2 (randomization part)
Overall Number of Participants Analyzed 50 31
Median (95% Confidence Interval)
Unit of Measure: Months
3.3
(2.1 to 4.7)
2.0
(1.8 to 2.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib, Placebo
Comments Compare PFS between the Sorafenib arm and the placebo arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the duration from randomization to death or last known alive. Only randomized patients were included in this analysis.
Time Frame Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:
Patients initially received Sorafenib in Step 2 (randomization part)
Patients initially received placebo in Step 2 (randomization part)
Overall Number of Participants Analyzed 50 31
Median (95% Confidence Interval)
Unit of Measure: Months
13.7
(7.9 to 17.8)
9.0
(6.7 to 11.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Sorafenib, Placebo
Comments Compare OS between the Sorafenib arm and the placebo arm
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.12
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
4.Secondary Outcome
Title Best Overall Response
Hide Description The best overall response is the best response (per RECIST 1.0) recorded from randomization until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since randomization.
Time Frame Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Sorafenib Placebo
Hide Arm/Group Description:
Patients initially received Sorafenib in Step 2 (randomization part)
Patients initially received placebo in Step 2 (randomization part)
Overall Number of Participants Analyzed 50 31
Measure Type: Number
Unit of Measure: Participants
Complete Response 0 0
Partial Response 1 1
Stable Disease 28 6
Progression 20 24
Unevaluable 1 0
Time Frame Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Induction: Sorafenib Randomization (Step 2): Sorafenib Randomization (Step 2): Placebo Randomization (Step 2): Mixed Crossover: Sorafenib
Hide Arm/Group Description All patients who received induction treatment (333 patients), regardless of eligibility status, were included in the toxicity analysis. After induction treatment, 59 patients were randomized to the sorafenib arm. Among these, 55 received treatment. However, due to drug dispensing error, 10 of them received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities. As a result, 45 treated patients were included in the "randomization (step 2): sorafenib" group. After induction treatment, 46 patients were randomized to the placebo arm. Among these, 40 received treatment. However, due to drug dispensing error, 2 of them received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities. As a result, 38 treated patients were included in the "randomization (step 2): placebo" group. After induction treatment, patients with stable disease were randomized to receive either sorafenib or placebo. Due to drug dispensing error, 10 patients from the sorafenib arm and 2 patients from the placebo arm (12 pts in total) received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities. Patients on the placebo arm who develop progressive disease may cross over to receive sorafenib, and 27 patients from the placebo arm received sorafenib in Step 3 (crossover). Due to drug dispensing error, even though some patients actually received straight sorafenib during Step 2 (randomization) treatment, they were thought to be randomized onto the placebo arm upon progression and unblinding (before finding out the fact of the dispensing error). Consequently, these patients were crossed over to Step 3, and there were 10 of them. In total, 37 patients registered to step 3 (crossover). Of these, 35 patients received treatment and were included in the toxicity analysis for the crossover (step 3) part.
All-Cause Mortality
Induction: Sorafenib Randomization (Step 2): Sorafenib Randomization (Step 2): Placebo Randomization (Step 2): Mixed Crossover: Sorafenib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Induction: Sorafenib Randomization (Step 2): Sorafenib Randomization (Step 2): Placebo Randomization (Step 2): Mixed Crossover: Sorafenib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   133/333 (39.94%)   16/45 (35.56%)   7/38 (18.42%)   2/12 (16.67%)   15/35 (42.86%) 
Blood and lymphatic system disorders           
Anemia  1  1/333 (0.30%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Hemolysis  1  0/333 (0.00%)  0/45 (0.00%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Cardiac disorders           
Atrial fibrillation  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Hypotension  1  0/333 (0.00%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Left ventricular systolic dysfunction  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Restrictive cardiomyopathy  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Supraventricular tachycardia  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Endocrine disorders           
Hypothyroidism  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Gastrointestinal disorders           
Abdomen, pain  1  4/333 (1.20%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  2/35 (5.71%) 
Constipation  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Diarrhea w/o prior colostomy  1  5/333 (1.50%)  2/45 (4.44%)  0/38 (0.00%)  0/12 (0.00%)  2/35 (5.71%) 
Distention/bloating, abdominal  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Muco/stomatitis (symptom), oral cavity  1  2/333 (0.60%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Muco/stomatitis by exam, oral cavity  1  1/333 (0.30%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Nausea  1  6/333 (1.80%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  2/35 (5.71%) 
Oral gums, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Stomach, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Vomiting  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
General disorders           
Chest/thoracic pain NOS  1  3/333 (0.90%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Death - disease progression NOS  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Fatigue  1  35/333 (10.51%)  3/45 (6.67%)  2/38 (5.26%)  1/12 (8.33%)  6/35 (17.14%) 
Sudden death  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Immune system disorders           
Allergic reaction  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Infections and infestations           
Infection - other  1  1/333 (0.30%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Infection with Grade 0-2 neutropenia, lung  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Infection with Grade 3-4 neutropenia, lung  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Infection with unknown ANC, lung  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Lymphopenia  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Injury, poisoning and procedural complications           
Thrombosis/embolism (Vascular access-related)  1  0/333 (0.00%)  0/45 (0.00%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Thrombosis/thrombus/embolism  1  8/333 (2.40%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Investigations           
ALT increased  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
AST increased  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Alkaline phosphatase increased  1  2/333 (0.60%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Bilirubin increased  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
GGT  1  0/333 (0.00%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
INR  1  6/333 (1.80%)  3/45 (6.67%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Lipase increased  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Neutropenia  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Prolonged QTc interval  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Thrombocytopenia  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Weight loss  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  2/35 (5.71%) 
Metabolism and nutrition disorders           
Anorexia  1  10/333 (3.00%)  0/45 (0.00%)  1/38 (2.63%)  0/12 (0.00%)  1/35 (2.86%) 
Dehydration  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Hyperkalemia  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Hypoalbuminemia  1  1/333 (0.30%)  0/45 (0.00%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Hyponatremia  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Hypophosphatemia  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back, pain  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Bone, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Chest wall, pain  1  0/333 (0.00%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Extremity-limb, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Joint, pain  1  6/333 (1.80%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Muscle, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Nonneuropathic generalized weakness  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Nervous system disorders           
Ataxia  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
CNS cerebrovascular ischemia  1  4/333 (1.20%)  1/45 (2.22%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Cognitive disturbance  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Dizziness  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Head/headache  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Memory impairment  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Neurologic - other  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Neuropathy - motor  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Neuropathy - sensory  1  4/333 (1.20%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Ocular - other  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Seizure  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Speech impairment  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Syncope  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Psychiatric disorders           
Confusion  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Renal and urinary disorders           
Renal failure  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Bronchopulmonary hemorrhage  1  3/333 (0.90%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Dyspnea  1  11/333 (3.30%)  1/45 (2.22%)  1/38 (2.63%)  1/12 (8.33%)  1/35 (2.86%) 
Hypoxia  1  3/333 (0.90%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Nose, hemorrhage  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Pleural effusion (non-malignant)  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Pneumonitis/pulmonary infiltrates  1  4/333 (1.20%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Pneumothorax  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Pulmonary hypertension  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Respiratory tract hemorrhage NOS  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  1/35 (2.86%) 
Skin and subcutaneous tissue disorders           
Hand-foot reaction  1  32/333 (9.61%)  2/45 (4.44%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Photosensitivity  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Pruritus/itching  1  3/333 (0.90%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Rash/desquamation  1  21/333 (6.31%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  0/35 (0.00%) 
Vascular disorders           
Hypertension  1  10/333 (3.00%)  1/45 (2.22%)  1/38 (2.63%)  0/12 (0.00%)  2/35 (5.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction: Sorafenib Randomization (Step 2): Sorafenib Randomization (Step 2): Placebo Randomization (Step 2): Mixed Crossover: Sorafenib
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   307/333 (92.19%)   42/45 (93.33%)   34/38 (89.47%)   11/12 (91.67%)   35/35 (100.00%) 
Blood and lymphatic system disorders           
Anemia  1  96/333 (28.83%)  16/45 (35.56%)  15/38 (39.47%)  3/12 (25.00%)  17/35 (48.57%) 
Gastrointestinal disorders           
Constipation  1  30/333 (9.01%)  8/45 (17.78%)  0/38 (0.00%)  1/12 (8.33%)  3/35 (8.57%) 
Diarrhea w/o prior colostomy  1  87/333 (26.13%)  15/45 (33.33%)  5/38 (13.16%)  9/12 (75.00%)  19/35 (54.29%) 
Dyspepsia  1  30/333 (9.01%)  4/45 (8.89%)  2/38 (5.26%)  1/12 (8.33%)  3/35 (8.57%) 
Muco/stomatitis by exam, oral cavity  1  28/333 (8.41%)  2/45 (4.44%)  1/38 (2.63%)  0/12 (0.00%)  1/35 (2.86%) 
Muco/stomatitis (symptom), oral cavity  1  39/333 (11.71%)  3/45 (6.67%)  2/38 (5.26%)  0/12 (0.00%)  1/35 (2.86%) 
Nausea  1  65/333 (19.52%)  12/45 (26.67%)  6/38 (15.79%)  2/12 (16.67%)  13/35 (37.14%) 
Vomiting  1  33/333 (9.91%)  6/45 (13.33%)  3/38 (7.89%)  0/12 (0.00%)  4/35 (11.43%) 
Dysphagia  1  8/333 (2.40%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  3/35 (8.57%) 
Flatulence  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  4/35 (11.43%) 
Taste disturbance  1  13/333 (3.90%)  3/45 (6.67%)  1/38 (2.63%)  2/12 (16.67%)  2/35 (5.71%) 
Abdomen, pain  1  10/333 (3.00%)  2/45 (4.44%)  4/38 (10.53%)  0/12 (0.00%)  3/35 (8.57%) 
Incontinence, anal  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Oral cavity, pain  1  4/333 (1.20%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
General disorders           
Fatigue  1  156/333 (46.85%)  24/45 (53.33%)  16/38 (42.11%)  7/12 (58.33%)  20/35 (57.14%) 
Fever w/o neutropenia  1  7/333 (2.10%)  0/45 (0.00%)  1/38 (2.63%)  0/12 (0.00%)  2/35 (5.71%) 
Rigors/chills  1  3/333 (0.90%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  4/35 (11.43%) 
Edema head and neck  1  8/333 (2.40%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Infections and infestations           
Infection Grade 0-2 neutropenia, upper airway  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Injury, poisoning and procedural complications           
Wound - non-infectious  1  2/333 (0.60%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Investigations           
Leukopenia  1  35/333 (10.51%)  5/45 (11.11%)  1/38 (2.63%)  1/12 (8.33%)  6/35 (17.14%) 
Thrombocytopenia  1  36/333 (10.81%)  4/45 (8.89%)  5/38 (13.16%)  0/12 (0.00%)  6/35 (17.14%) 
Weight loss  1  37/333 (11.11%)  5/45 (11.11%)  5/38 (13.16%)  2/12 (16.67%)  7/35 (20.00%) 
INR increased  1  20/333 (6.01%)  4/45 (8.89%)  2/38 (5.26%)  1/12 (8.33%)  1/35 (2.86%) 
Alkaline phosphatase increased  1  73/333 (21.92%)  10/45 (22.22%)  6/38 (15.79%)  2/12 (16.67%)  7/35 (20.00%) 
ALT increased  1  26/333 (7.81%)  7/45 (15.56%)  6/38 (15.79%)  1/12 (8.33%)  5/35 (14.29%) 
AST increased  1  50/333 (15.02%)  12/45 (26.67%)  5/38 (13.16%)  2/12 (16.67%)  10/35 (28.57%) 
Lymphopenia  1  5/333 (1.50%)  0/45 (0.00%)  0/38 (0.00%)  0/12 (0.00%)  2/35 (5.71%) 
Bilirubin increased  1  14/333 (4.20%)  1/45 (2.22%)  1/38 (2.63%)  1/12 (8.33%)  2/35 (5.71%) 
Creatinine increased  1  7/333 (2.10%)  1/45 (2.22%)  4/38 (10.53%)  0/12 (0.00%)  2/35 (5.71%) 
Weight gain  1  0/333 (0.00%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Metabolism and nutrition disorders           
Anorexia  1  104/333 (31.23%)  16/45 (35.56%)  6/38 (15.79%)  2/12 (16.67%)  9/35 (25.71%) 
Hypoalbuminemia  1  5/333 (1.50%)  0/45 (0.00%)  2/38 (5.26%)  0/12 (0.00%)  0/35 (0.00%) 
Musculoskeletal and connective tissue disorders           
Joint, pain  1  20/333 (6.01%)  2/45 (4.44%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Extremity-limb, pain  1  16/333 (4.80%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  2/35 (5.71%) 
Back, pain  1  11/333 (3.30%)  4/45 (8.89%)  1/38 (2.63%)  0/12 (0.00%)  0/35 (0.00%) 
Nervous system disorders           
Neuropathy - sensory  1  30/333 (9.01%)  5/45 (11.11%)  1/38 (2.63%)  2/12 (16.67%)  3/35 (8.57%) 
Head/headache  1  24/333 (7.21%)  6/45 (13.33%)  1/38 (2.63%)  0/12 (0.00%)  1/35 (2.86%) 
Dizziness  1  10/333 (3.00%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Neuropathy - motor  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  1/35 (2.86%) 
Psychiatric disorders           
Insomnia  1  6/333 (1.80%)  1/45 (2.22%)  1/38 (2.63%)  1/12 (8.33%)  0/35 (0.00%) 
Depression  1  5/333 (1.50%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders           
Cough  1  17/333 (5.11%)  4/45 (8.89%)  4/38 (10.53%)  0/12 (0.00%)  1/35 (2.86%) 
Dyspnea  1  22/333 (6.61%)  6/45 (13.33%)  4/38 (10.53%)  0/12 (0.00%)  3/35 (8.57%) 
Throat/pharynx/larynx, pain  1  1/333 (0.30%)  0/45 (0.00%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Voice changes/dysarthria  1  7/333 (2.10%)  1/45 (2.22%)  0/38 (0.00%)  1/12 (8.33%)  0/35 (0.00%) 
Skin and subcutaneous tissue disorders           
Dry skin  1  32/333 (9.61%)  8/45 (17.78%)  2/38 (5.26%)  1/12 (8.33%)  3/35 (8.57%) 
Alopecia  1  24/333 (7.21%)  11/45 (24.44%)  1/38 (2.63%)  1/12 (8.33%)  5/35 (14.29%) 
Pruritus/itching  1  56/333 (16.82%)  6/45 (13.33%)  1/38 (2.63%)  1/12 (8.33%)  2/35 (5.71%) 
Rash/desquamation  1  115/333 (34.53%)  18/45 (40.00%)  9/38 (23.68%)  7/12 (58.33%)  10/35 (28.57%) 
Hand-foot reaction  1  48/333 (14.41%)  10/45 (22.22%)  2/38 (5.26%)  3/12 (25.00%)  5/35 (14.29%) 
Rash: acne/acneiform  1  4/333 (1.20%)  1/45 (2.22%)  1/38 (2.63%)  0/12 (0.00%)  2/35 (5.71%) 
Vascular disorders           
Hypertension  1  28/333 (8.41%)  6/45 (13.33%)  1/38 (2.63%)  0/12 (0.00%)  1/35 (2.86%) 
Flushing  1  12/333 (3.60%)  0/45 (0.00%)  2/38 (5.26%)  0/12 (0.00%)  3/35 (8.57%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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: Study Statistician
Organization: Eastern Cooperative Oncology Group (ECOG) Statistical Office
Phone: 617-632-3012
Layout table for additonal information
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00064350     History of Changes
Other Study ID Numbers: CDR0000315383
E2501 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted: July 8, 2003
First Posted: July 9, 2003
Results First Submitted: March 8, 2012
Results First Posted: November 28, 2012
Last Update Posted: November 30, 2015