Trial Outcomes & Findings for Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer (NCT NCT00064350)
NCT ID: NCT00064350
Last Updated: 2023-06-29
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
342 participants
Primary outcome timeframe
Two months after randomization
Results posted on
2023-06-29
Participant Flow
The first patient was accrued on May 28, 2004.
Participant milestones
| Measure |
Induction Then Sorafenib
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 Then Placebo Then Sorafenib
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, Not Randomized
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.
|
|---|---|---|---|
|
Induction Treatment
STARTED
|
59
|
46
|
237
|
|
Induction Treatment
Treated
|
59
|
46
|
228
|
|
Induction Treatment
Eligible and Treated
|
59
|
46
|
194
|
|
Induction Treatment
COMPLETED
|
51
|
37
|
1
|
|
Induction Treatment
NOT COMPLETED
|
8
|
9
|
236
|
|
Randomization
STARTED
|
59
|
46
|
0
|
|
Randomization
Treated
|
55
|
40
|
0
|
|
Randomization
Eligible and Treated
|
50
|
31
|
0
|
|
Randomization
COMPLETED
|
33
|
28
|
0
|
|
Randomization
NOT COMPLETED
|
26
|
18
|
0
|
|
Cross-Over
STARTED
|
10
|
27
|
0
|
|
Cross-Over
Treated
|
9
|
26
|
0
|
|
Cross-Over
Eligible and Treated
|
7
|
21
|
0
|
|
Cross-Over
COMPLETED
|
4
|
13
|
0
|
|
Cross-Over
NOT COMPLETED
|
6
|
14
|
0
|
Reasons for withdrawal
| Measure |
Induction Then Sorafenib
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 Then Placebo Then Sorafenib
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, Not Randomized
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.
|
|---|---|---|---|
|
Induction Treatment
Disease Progression
|
5
|
1
|
110
|
|
Induction Treatment
Adverse Event
|
0
|
2
|
49
|
|
Induction Treatment
Death
|
0
|
0
|
9
|
|
Induction Treatment
Withdrawal by Subject
|
0
|
0
|
21
|
|
Induction Treatment
Ineligible or never started treatment
|
3
|
6
|
34
|
|
Induction Treatment
Other
|
0
|
0
|
13
|
|
Randomization
Adverse Event
|
8
|
3
|
0
|
|
Randomization
Death
|
3
|
0
|
0
|
|
Randomization
Withdrawal by Subject
|
1
|
0
|
0
|
|
Randomization
Ineligible or never started treatment
|
9
|
15
|
0
|
|
Randomization
Other
|
5
|
0
|
0
|
|
Cross-Over
Adverse Event
|
0
|
1
|
0
|
|
Cross-Over
Death
|
1
|
3
|
0
|
|
Cross-Over
Withdrawal by Subject
|
2
|
2
|
0
|
|
Cross-Over
Ineligible or never started treatment
|
3
|
6
|
0
|
|
Cross-Over
Other
|
0
|
2
|
0
|
Baseline Characteristics
Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Induction Then Sorafenib
n=50 Participants
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 Then Placebo Then Sorafenib
n=31 Participants
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, Not Randomized
n=218 Participants
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
n=299 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
64.5 years
n=5 Participants
|
69 years
n=7 Participants
|
63 years
n=5 Participants
|
64 years
n=4 Participants
|
|
Sex/Gender, Customized
Female
|
27 participants
n=5 Participants
|
13 participants
n=7 Participants
|
90 participants
n=5 Participants
|
130 participants
n=4 Participants
|
|
Sex/Gender, Customized
Male
|
23 participants
n=5 Participants
|
18 participants
n=7 Participants
|
127 participants
n=5 Participants
|
168 participants
n=4 Participants
|
|
Sex/Gender, Customized
Unknown
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Two months after randomizationPer 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
Outcome measures
| Measure |
Sorafenib
n=50 Participants
Patients initially received Sorafenib in Step 2 (randomization part)
|
Placebo
n=31 Participants
Patients initially received placebo in Step 2 (randomization part)
|
|---|---|---|
|
Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
Response
|
0 participants
|
0 participants
|
|
Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
Stable Disease
|
27 participants
|
7 participants
|
|
Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
Progression
|
19 participants
|
23 participants
|
|
Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
Unevaluable
|
4 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 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.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.
Outcome measures
| Measure |
Sorafenib
n=50 Participants
Patients initially received Sorafenib in Step 2 (randomization part)
|
Placebo
n=31 Participants
Patients initially received placebo in Step 2 (randomization part)
|
|---|---|---|
|
Progression-free Survival
|
3.3 Months
Interval 2.1 to 4.7
|
2.0 Months
Interval 1.8 to 2.3
|
SECONDARY outcome
Timeframe: 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 yearsOverall survival is defined as the duration from randomization to death or last known alive. Only randomized patients were included in this analysis.
Outcome measures
| Measure |
Sorafenib
n=50 Participants
Patients initially received Sorafenib in Step 2 (randomization part)
|
Placebo
n=31 Participants
Patients initially received placebo in Step 2 (randomization part)
|
|---|---|---|
|
Overall Survival
|
13.7 Months
Interval 7.9 to 17.8
|
9.0 Months
Interval 6.7 to 11.7
|
SECONDARY outcome
Timeframe: 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 yearsThe 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.
Outcome measures
| Measure |
Sorafenib
n=50 Participants
Patients initially received Sorafenib in Step 2 (randomization part)
|
Placebo
n=31 Participants
Patients initially received placebo in Step 2 (randomization part)
|
|---|---|---|
|
Best Overall Response
Progression
|
20 Participants
|
24 Participants
|
|
Best Overall Response
Unevaluable
|
1 Participants
|
0 Participants
|
|
Best Overall Response
Complete Response
|
0 Participants
|
0 Participants
|
|
Best Overall Response
Partial Response
|
1 Participants
|
1 Participants
|
|
Best Overall Response
Stable Disease
|
28 Participants
|
6 Participants
|
Adverse Events
Induction: Sorafenib
Serious events: 133 serious events
Other events: 307 other events
Deaths: 0 deaths
Randomization (Step 2): Sorafenib
Serious events: 16 serious events
Other events: 42 other events
Deaths: 0 deaths
Randomization (Step 2): Placebo
Serious events: 7 serious events
Other events: 34 other events
Deaths: 0 deaths
Randomization (Step 2): Mixed
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Crossover: Sorafenib
Serious events: 15 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Induction: Sorafenib
n=333 participants at risk
All patients who received induction treatment (333 patients), regardless of eligibility status, were included in the toxicity analysis.
|
Randomization (Step 2): Sorafenib
n=45 participants at risk
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.
|
Randomization (Step 2): Placebo
n=38 participants at risk
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.
|
Randomization (Step 2): Mixed
n=12 participants at risk
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.
|
Crossover: Sorafenib
n=35 participants at risk
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.
|
|---|---|---|---|---|---|
|
Cardiac disorders
Hypotension
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Endocrine disorders
Hypothyroidism
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.90%
3/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
INR
|
1.8%
6/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
6.7%
3/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Infection - other
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Infection with Grade 0-2 neutropenia, lung
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Infection with Grade 3-4 neutropenia, lung
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Infection with unknown ANC, lung
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Joint, pain
|
1.8%
6/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Lipase increased
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Lymphopenia
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Memory impairment
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
ALT increased
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
AST increased
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Abdomen, pain
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Alkaline phosphatase increased
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Immune system disorders
Allergic reaction
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Blood and lymphatic system disorders
Anemia
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
3.0%
10/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Ataxia
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Cardiac disorders
Atrial fibrillation
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Back, pain
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Bilirubin increased
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Bone, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
0.90%
3/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
CNS cerebrovascular ischemia
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Chest wall, pain
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Chest/thoracic pain NOS
|
0.90%
3/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Cognitive disturbance
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Psychiatric disorders
Confusion
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Constipation
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Death - disease progression NOS
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
4.4%
2/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Distention/bloating, abdominal
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Dizziness
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.3%
11/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Extremity-limb, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Fatigue
|
10.5%
35/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
6.7%
3/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
17.1%
6/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
GGT
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Hand-foot reaction
|
9.6%
32/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
4.4%
2/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Head/headache
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Blood and lymphatic system disorders
Hemolysis
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Vascular disorders
Hypertension
|
3.0%
10/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Muco/stomatitis (symptom), oral cavity
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Muco/stomatitis by exam, oral cavity
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Nausea
|
1.8%
6/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Neurologic - other
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Neuropathy - motor
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Neuropathy - sensory
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Neutropenia
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Nose, hemorrhage
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Ocular - other
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Oral gums, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Prolonged QTc interval
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
0.90%
3/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
6.3%
21/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Renal and urinary disorders
Renal failure
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract hemorrhage NOS
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Seizure
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Speech impairment
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Stomach, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Sudden death
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Syncope
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Thrombocytopenia
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Injury, poisoning and procedural complications
Thrombosis/embolism (Vascular access-related)
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Injury, poisoning and procedural complications
Thrombosis/thrombus/embolism
|
2.4%
8/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Weight loss
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
Other adverse events
| Measure |
Induction: Sorafenib
n=333 participants at risk
All patients who received induction treatment (333 patients), regardless of eligibility status, were included in the toxicity analysis.
|
Randomization (Step 2): Sorafenib
n=45 participants at risk
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.
|
Randomization (Step 2): Placebo
n=38 participants at risk
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.
|
Randomization (Step 2): Mixed
n=12 participants at risk
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.
|
Crossover: Sorafenib
n=35 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
28.8%
96/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
35.6%
16/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
39.5%
15/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
25.0%
3/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
48.6%
17/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Leukopenia
|
10.5%
35/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.1%
5/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
17.1%
6/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Thrombocytopenia
|
10.8%
36/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.9%
4/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.2%
5/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
17.1%
6/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Vascular disorders
Hypertension
|
8.4%
28/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.3%
6/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Fatigue
|
46.8%
156/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
53.3%
24/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
42.1%
16/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
58.3%
7/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
57.1%
20/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Weight loss
|
11.1%
37/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.1%
5/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.2%
5/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
20.0%
7/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
INR increased
|
6.0%
20/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.9%
4/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.6%
32/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
17.8%
8/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.2%
24/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
24.4%
11/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
14.3%
5/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
16.8%
56/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.3%
6/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
34.5%
115/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
40.0%
18/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
23.7%
9/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
58.3%
7/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
28.6%
10/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Hand-foot reaction
|
14.4%
48/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
22.2%
10/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
25.0%
3/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
14.3%
5/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
31.2%
104/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
35.6%
16/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
15.8%
6/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
25.7%
9/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Constipation
|
9.0%
30/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
17.8%
8/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
26.1%
87/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
33.3%
15/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.2%
5/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
75.0%
9/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
54.3%
19/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
9.0%
30/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.9%
4/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Muco/stomatitis by exam, oral cavity
|
8.4%
28/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
4.4%
2/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Muco/stomatitis (symptom), oral cavity
|
11.7%
39/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
6.7%
3/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Nausea
|
19.5%
65/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
26.7%
12/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
15.8%
6/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
37.1%
13/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
9.9%
33/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.3%
6/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
7.9%
3/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.4%
4/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Alkaline phosphatase increased
|
21.9%
73/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
22.2%
10/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
15.8%
6/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
20.0%
7/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
ALT increased
|
7.8%
26/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
15.6%
7/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
15.8%
6/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
14.3%
5/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
AST increased
|
15.0%
50/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
26.7%
12/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.2%
5/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
28.6%
10/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Neuropathy - sensory
|
9.0%
30/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.1%
5/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Head/headache
|
7.2%
24/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.3%
6/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Joint, pain
|
6.0%
20/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
4.4%
2/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
17/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.9%
4/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
10.5%
4/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.6%
22/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
13.3%
6/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
10.5%
4/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Lymphopenia
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Fever w/o neutropenia
|
2.1%
7/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Rigors/chills
|
0.90%
3/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.4%
4/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Vascular disorders
Flushing
|
3.6%
12/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Dysphagia
|
2.4%
8/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Flatulence
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
11.4%
4/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Taste disturbance
|
3.9%
13/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
6.7%
3/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
16.7%
2/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Bilirubin increased
|
4.2%
14/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Creatinine increased
|
2.1%
7/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
10.5%
4/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Abdomen, pain
|
3.0%
10/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
4.4%
2/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
10.5%
4/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.6%
3/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Extremity-limb, pain
|
4.8%
16/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.7%
2/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Back, pain
|
3.3%
11/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.9%
4/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
5.3%
2/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Psychiatric disorders
Insomnia
|
1.8%
6/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.6%
1/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Investigations
Weight gain
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Injury, poisoning and procedural complications
Wound - non-infectious
|
0.60%
2/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Incontinence, anal
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Infections and infestations
Infection Grade 0-2 neutropenia, upper airway
|
0.00%
0/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
General disorders
Edema head and neck
|
2.4%
8/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Dizziness
|
3.0%
10/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Psychiatric disorders
Depression
|
1.5%
5/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Nervous system disorders
Neuropathy - motor
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.9%
1/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Gastrointestinal disorders
Oral cavity, pain
|
1.2%
4/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Throat/pharynx/larynx, pain
|
0.30%
1/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Voice changes/dysarthria
|
2.1%
7/333 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
2.2%
1/45 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/38 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
8.3%
1/12 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
0.00%
0/35 • Assessed every 4 weeks while on treatment and for 28 days after the end of treatment
|
Additional Information
Study Statistician
Eastern Cooperative Oncology Group (ECOG) Statistical Office
Phone: 617-632-3012
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place