Trial Outcomes & Findings for Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye (NCT NCT01143402)
NCT ID: NCT01143402
Last Updated: 2017-07-26
Results Overview
The primary analysis will be performed among the Gnaq/Gna11 mutant patients. A stratified logrank test will be performed stratified by mutation status, M stage, and number of prior systemic therapies for metastatic disease. Due to the potential for a large number of strata and small strata sizes, the standard asymptotic stratified logrank test will be verified for robustness utilizing a permutation reference distribution.
COMPLETED
PHASE2
120 participants
The time from randomization to the earlier date of objective disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or death due to any cause in the absence of progression, assessed up to 5 years
2017-07-26
Participant Flow
Participant milestones
| Measure |
Arm I (Temozolomide)
Randomized to Temozolomide
|
Arm II (Selumetinib)
Randomized to Selumetinib
|
Non-Randomized (Selumetinib)
Non-Randomized to Selumetinib
|
|---|---|---|---|
|
Overall Study
STARTED
|
51
|
50
|
19
|
|
Overall Study
COMPLETED
|
50
|
49
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
1
|
Reasons for withdrawal
| Measure |
Arm I (Temozolomide)
Randomized to Temozolomide
|
Arm II (Selumetinib)
Randomized to Selumetinib
|
Non-Randomized (Selumetinib)
Non-Randomized to Selumetinib
|
|---|---|---|---|
|
Overall Study
Rapid clinical decline
|
1
|
1
|
0
|
|
Overall Study
Not Treated
|
0
|
0
|
1
|
Baseline Characteristics
Temozolomide or Selumetinib in Treating Patients With Metastatic Melanoma of the Eye
Baseline characteristics by cohort
| Measure |
Arm I (Temozolomide)
n=51 Participants
Randomized to Temozolomide
|
Arm II (Selumetinib)
n=50 Participants
Randomized to Selumetinib
|
Non-Randomized (Selumetinib)
n=19 Participants
Non-Randomized to Selumetinib
|
Total
n=120 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
62 years
n=5 Participants
|
62 years
n=7 Participants
|
63 years
n=5 Participants
|
62 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
66 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: The time from randomization to the earlier date of objective disease progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or death due to any cause in the absence of progression, assessed up to 5 yearsPopulation: Analysis of progression-free survival in all evaluable randomized patients
The primary analysis will be performed among the Gnaq/Gna11 mutant patients. A stratified logrank test will be performed stratified by mutation status, M stage, and number of prior systemic therapies for metastatic disease. Due to the potential for a large number of strata and small strata sizes, the standard asymptotic stratified logrank test will be verified for robustness utilizing a permutation reference distribution.
Outcome measures
| Measure |
Arm I (Temozolomide)
n=49 Participants
Randomized to Temozolomide
|
Arm II (Selumetinib)
n=47 Participants
Randomized to Selumetinib
|
|---|---|---|
|
Progression-free Survival (PFS) (Evaluable Randomized Patients)
|
7 weeks
Interval 4.3 to 8.4
|
15.9 weeks
Interval 8.4 to 21.1
|
SECONDARY outcome
Timeframe: The time from randomization to death due to any cause, assessed up to 5 yearsThe primary analysis will be performed among the Gnaq/Gna11 mutant patients. A stratified logrank test will be performed stratified by mutation status, M stage, and number of prior systemic therapies for metastatic disease. Due to the potential for a large number of strata and small strata sizes, the standard asymptotic stratified logrank test will be verified for robustness utilizing a permutation reference distribution.
Outcome measures
| Measure |
Arm I (Temozolomide)
n=50 Participants
Randomized to Temozolomide
|
Arm II (Selumetinib)
n=49 Participants
Randomized to Selumetinib
|
|---|---|---|
|
Median Overall Survival (Evaluable Randomized Patients)
|
9.1 Months
Interval 6.1 to 11.1
|
11.8 Months
Interval 9.8 to 15.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed up to 5 yearsper Response Evaluation Criteria In Solid Tumors (RECIST) criteria or death due to any cause in the absence of progression
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: The time from randomization to death due to any cause, assessed up to 5 yearsThe primary analysis will be performed among the Gnaq/Gna11 mutant patients. A stratified logrank test will be performed stratified by mutation status, M stage, and number of prior systemic therapies for metastatic disease. Due to the potential for a large number of strata and small strata sizes, the standard asymptotic stratified logrank test will be verified for robustness utilizing a permutation reference distribution.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsCalculated along with a 95% confidence interval.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsToxicity will be reported by type, frequency, and severity. Please see adverse events.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 monthsEvaluated using a Simon mini-max design. Curves will be generated using Kaplan-Meier methodology.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsChanges will be assessed by a Wilcoxon test
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 4 monthsCorrelated with disease status using Fishers exact test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 4 monthsCorrelated with disease status using Fishers exact test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 4 monthsDecrease in p-ERK will be correlated with disease status using Fishers exact test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 4 monthsCorrelated with disease status using Fishers exact test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to 60 minutes post injectionA paired student's t-test will be performed. Analysis of variance will also be performed to obtain the significance of FLT-PET uptake on each lesion between patients.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsSummarized using descriptive statistics for each assessment time and by treatment group. The scores will be compared between treatment groups using a mixed effect model for repeated measures analysis method. Treatment difference will be estimated from the model for each assessment time.
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Temozolomide)
Arm II (Selumetinib)
Non-Randomized (Selumetinib)
Serious adverse events
| Measure |
Arm I (Temozolomide)
n=50 participants at risk
Randomized to Temozolomide
|
Arm II (Selumetinib)
n=49 participants at risk
Randomized to Selumetinib
|
Non-Randomized (Selumetinib)
n=18 participants at risk
Non-Randomized to Selumetinib
|
|---|---|---|---|
|
General disorders
Abdominal pain
|
2.0%
1/50
|
4.1%
2/49
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Alanine aminotransferase increased
|
2.0%
1/50
|
4.1%
2/49
|
5.6%
1/18
|
|
General disorders
Ascites
|
2.0%
1/50
|
0.00%
0/49
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
CPK increased
|
8.0%
4/50
|
18.4%
9/49
|
11.1%
2/18
|
|
Metabolism and nutrition disorders
Creatinine increased
|
2.0%
1/50
|
0.00%
0/49
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
2.0%
1/50
|
0.00%
0/49
|
0.00%
0/18
|
|
Hepatobiliary disorders
Hepatic failure
|
2.0%
1/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
2.0%
1/50
|
0.00%
0/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
2.0%
1/50
|
0.00%
0/49
|
5.6%
1/18
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
2.0%
1/50
|
2.0%
1/49
|
0.00%
0/18
|
|
General disorders
Multi-organ failure
|
2.0%
1/50
|
0.00%
0/49
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Neoplasms
|
18.0%
9/50
|
6.1%
3/49
|
22.2%
4/18
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
2.0%
1/50
|
0.00%
0/49
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Skin infection
|
2.0%
1/50
|
2.0%
1/49
|
5.6%
1/18
|
|
Cardiac disorders
Supraventricular tachycardia
|
2.0%
1/50
|
0.00%
0/49
|
5.6%
1/18
|
|
Cardiac disorders
Thromboembolic event
|
2.0%
1/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Alkaline phosphatase increased
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Aspartate aminotransferase increased
|
0.00%
0/50
|
4.1%
2/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Blood bilirubin increased
|
0.00%
0/50
|
6.1%
3/49
|
5.6%
1/18
|
|
General disorders
Confusion
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
General disorders
Death NOS
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Gastrointestinal disorders
Dehydration
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/50
|
4.1%
2/49
|
0.00%
0/18
|
|
General disorders
Edema limbs
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
GGT increased
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/50
|
4.1%
2/49
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
0.00%
0/50
|
4.1%
2/49
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Nausea
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
General disorders
Syncope
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/50
|
2.0%
1/49
|
0.00%
0/18
|
|
General disorders
General Disorders
|
0.00%
0/50
|
0.00%
0/49
|
5.6%
1/18
|
Other adverse events
| Measure |
Arm I (Temozolomide)
n=50 participants at risk
Randomized to Temozolomide
|
Arm II (Selumetinib)
n=49 participants at risk
Randomized to Selumetinib
|
Non-Randomized (Selumetinib)
n=18 participants at risk
Non-Randomized to Selumetinib
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
16.0%
8/50
|
30.6%
15/49
|
33.3%
6/18
|
|
Blood and lymphatic system disorders
Leukopenia
|
18.0%
9/50
|
12.2%
6/49
|
33.3%
6/18
|
|
Blood and lymphatic system disorders
Lymphopenia
|
10.0%
5/50
|
8.2%
4/49
|
22.2%
4/18
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.0%
5/50
|
6.1%
3/49
|
16.7%
3/18
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.0%
8/50
|
10.2%
5/49
|
27.8%
5/18
|
|
Blood and lymphatic system disorders
Alanine Amino Transferase Elevation
|
8.0%
4/50
|
42.9%
21/49
|
38.9%
7/18
|
|
General disorders
Alopecia
|
0.00%
0/50
|
12.2%
6/49
|
5.6%
1/18
|
|
General disorders
Anorexia
|
14.0%
7/50
|
8.2%
4/49
|
5.6%
1/18
|
|
Musculoskeletal and connective tissue disorders
Arthralgias
|
0.00%
0/50
|
10.2%
5/49
|
0.00%
0/18
|
|
Blood and lymphatic system disorders
Aspartate Amino Transferase Elevation
|
12.0%
6/50
|
51.0%
25/49
|
38.9%
7/18
|
|
Eye disorders
Blurred Vision
|
0.00%
0/50
|
6.1%
3/49
|
5.6%
1/18
|
|
Gastrointestinal disorders
Constipation
|
30.0%
15/50
|
6.1%
3/49
|
5.6%
1/18
|
|
General disorders
CPK Elevation
|
0.00%
0/50
|
53.1%
26/49
|
77.8%
14/18
|
|
Gastrointestinal disorders
Diarrhea
|
8.0%
4/50
|
40.8%
20/49
|
44.4%
8/18
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/50
|
16.3%
8/49
|
11.1%
2/18
|
|
General disorders
Edema Face
|
0.00%
0/50
|
12.2%
6/49
|
16.7%
3/18
|
|
Eye disorders
Eye Disorder
|
0.00%
0/50
|
8.2%
4/49
|
5.6%
1/18
|
|
General disorders
Fatigue
|
44.0%
22/50
|
61.2%
30/49
|
44.4%
8/18
|
|
General disorders
Mucositis
|
2.0%
1/50
|
12.2%
6/49
|
0.00%
0/18
|
|
Gastrointestinal disorders
Nausea
|
40.0%
20/50
|
36.7%
18/49
|
38.9%
7/18
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
0.00%
0/50
|
16.3%
8/49
|
5.6%
1/18
|
|
Skin and subcutaneous tissue disorders
Rash Acneiform
|
6.0%
3/50
|
77.6%
38/49
|
66.7%
12/18
|
|
Gastrointestinal disorders
Vomiting
|
24.0%
12/50
|
22.4%
11/49
|
16.7%
3/18
|
|
General disorders
Edema Limbs
|
2.0%
1/50
|
30.6%
15/49
|
55.6%
10/18
|
Additional Information
Dr. Paul Chapman
Memorial Sloan Kettering Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60