Trial Outcomes & Findings for Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer (NCT NCT01208051)
NCT ID: NCT01208051
Last Updated: 2021-07-15
Results Overview
Dose limiting toxicity was defined as any of the following occurring during the first cycle (28 days) of therapy: Hematological toxicities: * Any grade 4 neutropenia (ANC \< 500) lasting more than 5 days * Any grade 4 neutropenia with concomitant fever (temperature \> 38.5) * Any grade 4 neutropenia and sepsis or other severe infection * Any grade 4 thrombocytopenia Any other grade 3-4 non-hematological adverse drug reactions, except untreated nausea/vomiting, or hypersensitivity reactions. Grade 4 hypertension Grade 4 proteinuria Delay in the administration of a subsequent dose of cediranib and lenalidomide exceeding 2 weeks, due to an adverse drug reaction
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
127 participants
Primary outcome timeframe
28 days
Results posted on
2021-07-15
Participant Flow
Participant milestones
| Measure |
Phase I Dose Level 0
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Total Enrollment
STARTED
|
4
|
7
|
6
|
39
|
71
|
|
Total Enrollment
COMPLETED
|
4
|
6
|
5
|
39
|
69
|
|
Total Enrollment
NOT COMPLETED
|
0
|
1
|
1
|
0
|
2
|
|
Interim Futility Analysis
STARTED
|
0
|
0
|
0
|
39
|
68
|
|
Interim Futility Analysis
COMPLETED
|
0
|
0
|
0
|
39
|
68
|
|
Interim Futility Analysis
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
After Crossover to Cediranib Only
STARTED
|
0
|
0
|
0
|
39
|
69
|
|
After Crossover to Cediranib Only
COMPLETED
|
0
|
0
|
0
|
39
|
69
|
|
After Crossover to Cediranib Only
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Phase I Dose Level 0
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Total Enrollment
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
2
|
|
Total Enrollment
Brain metastases
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Cediranib Maleate With or Without Lenalidomide for the Treatment of Thyroid Cancer
Baseline characteristics by cohort
| Measure |
Phase I Dose Level 0
n=4 Participants
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
Total
n=123 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
72.2 years
n=5 Participants
|
64.5 years
n=7 Participants
|
67.2 years
n=5 Participants
|
61.9 years
n=4 Participants
|
63.8 years
n=21 Participants
|
63.1 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
40 Participants
n=21 Participants
|
75 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
48 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
8 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
59 Participants
n=21 Participants
|
103 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
|
Region of Enrollment
Canada
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
5 participants
n=4 Participants
|
7 participants
n=21 Participants
|
12 participants
n=10 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
34 participants
n=4 Participants
|
62 participants
n=21 Participants
|
111 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: 28 daysPopulation: Dose limiting toxicity was no an endpoint for the phase II study.
Dose limiting toxicity was defined as any of the following occurring during the first cycle (28 days) of therapy: Hematological toxicities: * Any grade 4 neutropenia (ANC \< 500) lasting more than 5 days * Any grade 4 neutropenia with concomitant fever (temperature \> 38.5) * Any grade 4 neutropenia and sepsis or other severe infection * Any grade 4 thrombocytopenia Any other grade 3-4 non-hematological adverse drug reactions, except untreated nausea/vomiting, or hypersensitivity reactions. Grade 4 hypertension Grade 4 proteinuria Delay in the administration of a subsequent dose of cediranib and lenalidomide exceeding 2 weeks, due to an adverse drug reaction
Outcome measures
| Measure |
Phase I Dose Level 0
n=4 Participants
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Dose Limiting Toxicity
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Assessed up to 3 yearsPopulation: Phase I study did not have a futility analysis. For phase II, one patient in Arm B was enrolled while the futility analysis was ongoing.
Time from enrollment on study to disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. This analysis corresponds to the planned futility analysis after 40 events.
Outcome measures
| Measure |
Phase I Dose Level 0
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=68 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Progression-free Survival (Phase II Futility Analysis)
|
—
|
—
|
—
|
20.9 months
Interval 10.9 to
Upper limit not reached, too few events
|
10.6 months
Interval 7.3 to 14.6
|
PRIMARY outcome
Timeframe: Assessed up to 3 yearsTime from study enrollment until disease progression or death from any cause. Surviving patients without progression are censored as of the date of the last negative examination. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Phase I Dose Level 0
n=4 Participants
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Progression-free Survival (Final Results After Crossover)
|
NA months
Median not reached, too few events
|
14.8 months
Interval 3.5 to 30.9
|
23.6 months
Interval 2.5 to 49.5
|
14.8 months
Interval 8.5 to 23.8
|
11.3 months
Interval 8.7 to 18.9
|
SECONDARY outcome
Timeframe: Assessed up to 3 yearsPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
Phase I Dose Level 0
n=4 Participants
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Objective Response Rate
|
0 Participants
|
2 Participants
|
4 Participants
|
17 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: 24 monthsTime from randomization to death from any cause. Patients who have not died are censored as of the date last known alive.
Outcome measures
| Measure |
Phase I Dose Level 0
n=4 Participants
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 Participants
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Overall Survival (Final Results After Crossover)
|
NA percentage of participants
24 mo estimate not reached, too few events
|
60.0 percentage of participants
Interval 17.1 to 100.0
|
100 percentage of participants
Interval 73.5 to 100.0
|
64.8 percentage of participants
Interval 43.3 to 86.4
|
75.3 percentage of participants
Interval 59.4 to 91.0
|
SECONDARY outcome
Timeframe: From baseline to 2 monthsPopulation: Percent change in tumor size was not an endpoint for the phase I study.
The percent change in tumor size from baseline to the end of cycle 2 (two months). The post-treatment total sum of lengths for a patient with a new lesion at cycle 2 will be scored as 1.2\*max(pre-sum, post-sum) to ensure that the appearance of new lesions corresponds to a disease progression per Response Evaluation Criteria in Solid Tumors criteria. In the event of any early deaths prior to cycle 2, a nonparametric rank sum test will be used with deaths ranked at the extreme end of the distribution.
Outcome measures
| Measure |
Phase I Dose Level 0
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=38 Participants
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=63 Participants
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Percent Change in Tumor Size (Phase II)
|
—
|
—
|
—
|
-12.5 percent change
Interval -26.0 to 0.0
|
-4.2 percent change
Interval -25.0 to 0.0
|
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: These outcomes were not assessed in the Phase I study. These data were not collected and analyzed for the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.
Thyroid stimulating hormone and thyroglobulin levels
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 3 yearsPopulation: Mutations were not endpoints for the phase I study. These data were not collected and analyzed in the phase II study because combination treatment was stopped due to reaching futility criteria at interim analysis.
Presence or absence of B-RAF and RAS mutations at baseline--to be correlated with response rates, progression-free survival, and overall survival.
Outcome measures
Outcome data not reported
Adverse Events
Phase I Dose Level 0
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Phase I Dose Level +1
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase I Dose Level +2
Serious events: 5 serious events
Other events: 5 other events
Deaths: 0 deaths
Phase II Arm A (Cediranib Maleate)
Serious events: 16 serious events
Other events: 38 other events
Deaths: 8 deaths
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
Serious events: 32 serious events
Other events: 66 other events
Deaths: 13 deaths
Serious adverse events
| Measure |
Phase I Dose Level 0
n=4 participants at risk
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 participants at risk
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 participants at risk
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 participants at risk
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 participants at risk
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Mucositis oral
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Nervous system disorders
Seizure
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
General disorders
Fever
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Investigations
Blood bilirubin increase
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Infections and infestations
Bronchial infection
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Cardiac disorders
Chest pain - cardiac
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Nervous system disorders
Cognitive disturbance
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Investigations
Creatinine increased
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
General disorders
Death NOS
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Psychiatric disorders
Delirium
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Dysphagia, esophagitis, odynophagia
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
7.2%
5/69 • Up to 3 years
|
|
Cardiac disorders
Ejection fraction decreased
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Endocrine disorders
Endocrine disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Eye disorders
Eye disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
Fatigue
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
Flu like symptoms
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Hepatobiliary disorders
Gallbladder perforation
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
General disorders and administration site conditions - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Vascular disorders
Hematoma
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Infections and infestations
Lung infection
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benihn, malignant and unspecified - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
General disorders
Pain
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Infections and infestations
Prostate infection
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Infections and infestations
Skin infection
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Social circumstances
Social circumstances - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Soft tissue necrosis lower limb
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Nervous system disorders
Stroke
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
Sudden death NOS
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Surgical and medical procedures
Surgical and medical procedures - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Vascular disorders
Thromboembolic event
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Investigations
Weight loss
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Infections and infestations
Infections and infestations - Other
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Infections and infestations
Kidney infection
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
Other adverse events
| Measure |
Phase I Dose Level 0
n=4 participants at risk
Cediranib 20 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 15 days of a 28 day cycle)
|
Phase I Dose Level +1
n=6 participants at risk
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (21/28 days, i.e., given for 21 days of a 28 day cycle)
|
Phase I Dose Level +2
n=5 participants at risk
Cediranib 30 mg (28/28 days, i.e., given for 28 days of a 28 day cycle) + Lenalidomide 15 mg (28/28 days, i.e., given for 28 days of a 28 day cycle)
|
Phase II Arm A (Cediranib Maleate)
n=39 participants at risk
Patients receive cediranib maleate 30 mg PO QD on days 1-28. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
|
Phase II Arm B (Cediranib Maleate Plus Lenalidomide Thru April 10, 2015)
n=69 participants at risk
Patients receive cediranib maleate 30 mg PO and lenalidomide 15 mg PO on days 1-21. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: As of April 10, 2015, patients assigned to this arm are discontinued lenalidomide and continued on cediranib alone.
Cediranib: Given PO
Cediranib Maleate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
14.5%
10/69 • Up to 3 years
|
|
Investigations
Alanine aminotransferase increased
|
50.0%
2/4 • Up to 3 years
|
83.3%
5/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
30.8%
12/39 • Up to 3 years
|
44.9%
31/69 • Up to 3 years
|
|
Investigations
Alkaline phosphatase increased
|
50.0%
2/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
21.7%
15/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Blood and lymphatic system disorders
Anemia
|
25.0%
1/4 • Up to 3 years
|
50.0%
3/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
25.6%
10/39 • Up to 3 years
|
26.1%
18/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Anorexia
|
100.0%
4/4 • Up to 3 years
|
66.7%
4/6 • Up to 3 years
|
100.0%
5/5 • Up to 3 years
|
56.4%
22/39 • Up to 3 years
|
44.9%
31/69 • Up to 3 years
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
11.6%
8/69 • Up to 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
2/4 • Up to 3 years
|
83.3%
5/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
30.8%
12/39 • Up to 3 years
|
37.7%
26/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
25.6%
10/39 • Up to 3 years
|
11.6%
8/69 • Up to 3 years
|
|
Investigations
Blood bilirubin increased
|
25.0%
1/4 • Up to 3 years
|
66.7%
4/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
13.0%
9/69 • Up to 3 years
|
|
Eye disorders
Blurred visioin
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Gastrointestinal disorders
Constipation
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
30.8%
12/39 • Up to 3 years
|
34.8%
24/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
23.2%
16/69 • Up to 3 years
|
|
Investigations
Creatinine increase
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
21.7%
15/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
7.2%
5/69 • Up to 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
100.0%
4/4 • Up to 3 years
|
83.3%
5/6 • Up to 3 years
|
100.0%
5/5 • Up to 3 years
|
82.1%
32/39 • Up to 3 years
|
82.6%
57/69 • Up to 3 years
|
|
Nervous system disorders
Dizziness
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
14.5%
10/69 • Up to 3 years
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
23.1%
9/39 • Up to 3 years
|
11.6%
8/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
7.2%
5/69 • Up to 3 years
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
24.6%
17/69 • Up to 3 years
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
17.4%
12/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
50.0%
2/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
26.1%
18/69 • Up to 3 years
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
Edema limbs
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
14.5%
10/69 • Up to 3 years
|
|
Eye disorders
Eye disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
General disorders
Fatigue
|
100.0%
4/4 • Up to 3 years
|
100.0%
6/6 • Up to 3 years
|
100.0%
5/5 • Up to 3 years
|
79.5%
31/39 • Up to 3 years
|
82.6%
57/69 • Up to 3 years
|
|
General disorders
Fever
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
General disorders
General disorders and administration site conditions - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
11.6%
8/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Nervous system disorders
Headache
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
28.2%
11/39 • Up to 3 years
|
29.0%
20/69 • Up to 3 years
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/4 • Up to 3 years
|
50.0%
3/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
15.9%
11/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
1/4 • Up to 3 years
|
83.3%
5/6 • Up to 3 years
|
80.0%
4/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
18.8%
13/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Up to 3 years
|
50.0%
3/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
69.2%
27/39 • Up to 3 years
|
63.8%
44/69 • Up to 3 years
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
24.6%
17/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
75.0%
3/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
28.2%
11/39 • Up to 3 years
|
24.6%
17/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
25.0%
1/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
28.2%
11/39 • Up to 3 years
|
29.0%
20/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
18.8%
13/69 • Up to 3 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/4 • Up to 3 years
|
66.7%
4/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
13.0%
9/69 • Up to 3 years
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Infections and infestations
Infections and infestations - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Investigations
Investigations - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Investigations
Lymphocyte count decreased
|
50.0%
2/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
17.9%
7/39 • Up to 3 years
|
17.4%
12/69 • Up to 3 years
|
|
General disorders
Malaise
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Psychiatric disorders
Mood alteration-depression
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Gastrointestinal disorders
Mucositis oral
|
100.0%
4/4 • Up to 3 years
|
100.0%
6/6 • Up to 3 years
|
80.0%
4/5 • Up to 3 years
|
28.2%
11/39 • Up to 3 years
|
40.6%
28/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
43.6%
17/39 • Up to 3 years
|
43.5%
30/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
Nervous system disorders
Nervous system disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Nervous system disorders
Neuropathy-sensory
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
8.7%
6/69 • Up to 3 years
|
|
Investigations
Neutrophil count decreased
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
43.5%
30/69 • Up to 3 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Gastrointestinal disorders
Oral dysesthesia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
General disorders
Pain
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
28.2%
11/39 • Up to 3 years
|
17.4%
12/69 • Up to 3 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
38.5%
15/39 • Up to 3 years
|
24.6%
17/69 • Up to 3 years
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
12.8%
5/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Investigations
Platelet count decreased
|
50.0%
2/4 • Up to 3 years
|
50.0%
3/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
36.2%
25/69 • Up to 3 years
|
|
Renal and urinary disorders
Proteinuria
|
50.0%
2/4 • Up to 3 years
|
83.3%
5/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
46.2%
18/39 • Up to 3 years
|
34.8%
24/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
40.0%
2/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
15.9%
11/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
2.6%
1/39 • Up to 3 years
|
10.1%
7/69 • Up to 3 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Renal and urinary disorders
Renal calculi
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
15.4%
6/39 • Up to 3 years
|
11.6%
8/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
20.5%
8/39 • Up to 3 years
|
4.3%
3/69 • Up to 3 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Vascular disorders
Thromboembolic event
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
5.8%
4/69 • Up to 3 years
|
|
Nervous system disorders
Tremor
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
10.3%
4/39 • Up to 3 years
|
2.9%
2/69 • Up to 3 years
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
35.9%
14/39 • Up to 3 years
|
20.3%
14/69 • Up to 3 years
|
|
Investigations
Weight loss
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
41.0%
16/39 • Up to 3 years
|
29.0%
20/69 • Up to 3 years
|
|
Investigations
White blood cell decreased
|
50.0%
2/4 • Up to 3 years
|
33.3%
2/6 • Up to 3 years
|
60.0%
3/5 • Up to 3 years
|
7.7%
3/39 • Up to 3 years
|
40.6%
28/69 • Up to 3 years
|
|
General disorders
Flu like symptoms
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
5.1%
2/39 • Up to 3 years
|
1.4%
1/69 • Up to 3 years
|
|
Investigations
CD4 lymphocytes decreased
|
25.0%
1/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Investigations
Lymphocyte count increased
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Nervous system disorders
Transient ischemic attacks
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
General disorders
Multi-organ failure
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
General disorders
Salivary duct inflammation
|
0.00%
0/4 • Up to 3 years
|
16.7%
1/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Infections and infestations
Papulopustular rash
|
0.00%
0/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
20.0%
1/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
|
Investigations
Ejection fraction decreased
|
25.0%
1/4 • Up to 3 years
|
0.00%
0/6 • Up to 3 years
|
0.00%
0/5 • Up to 3 years
|
0.00%
0/39 • Up to 3 years
|
0.00%
0/69 • Up to 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60