Trial Outcomes & Findings for First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma (NCT NCT01828034)
NCT ID: NCT01828034
Last Updated: 2020-11-17
Results Overview
In the phase I portion, up to 18 patients will be enrolled in classic 3+3 cohort dose escalation design to identify the MTD of MEK162 when administered with gemcitabine and cisplatin given weeks 2 and 3 of a 3 week cycle .
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
42 participants
Primary outcome timeframe
1 year
Results posted on
2020-11-17
Participant Flow
Participant milestones
| Measure |
Cohort 1
Cohort 1
Phase I, Dose Level 1 - MEK162 25 mg
|
Cohort 2
Cohort 2 Phase I, Dose Level 2 - MEK162 45mg
|
Cohort 3
Cohort 3 Phase I, Dose Level 3 / Phase II - MTD mg
|
Cohort 4
Cohort 4 Phase II only, MTD mg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
6
|
3
|
30
|
|
Overall Study
COMPLETED
|
3
|
6
|
3
|
29
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Cohort 1
Cohort 1
Phase I, Dose Level 1 - MEK162 25 mg
|
Cohort 2
Cohort 2 Phase I, Dose Level 2 - MEK162 45mg
|
Cohort 3
Cohort 3 Phase I, Dose Level 3 / Phase II - MTD mg
|
Cohort 4
Cohort 4 Phase II only, MTD mg
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
Baseline Characteristics
First Line Gemcitabine, Cisplatin and MEK162 in Advanced Biliary Tract Carcinoma
Baseline characteristics by cohort
| Measure |
Cohort 1
n=3 Participants
Cohort 1 Phase I, Dose Level 1 - MEK162 25 mg
|
Cohort 2
n=6 Participants
Cohort 2 Phase I, Dose Level 2 - MEK162 45mg
|
Cohort 3
n=3 Participants
Cohort 3 Phase I, Dose Level 3 / Phase II - MTD mg
|
Cohort 4
n=29 Participants
Cohort 4 Phase II only, MTD mg
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
64.3 years
n=5 Participants
|
54.3 years
n=7 Participants
|
71.3 years
n=5 Participants
|
69 years
n=4 Participants
|
66 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
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
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
37 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
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
|
|
Race (NIH/OMB)
Asian
|
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
|
|
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
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
36 Participants
n=21 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
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
41 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 1 yearIn the phase I portion, up to 18 patients will be enrolled in classic 3+3 cohort dose escalation design to identify the MTD of MEK162 when administered with gemcitabine and cisplatin given weeks 2 and 3 of a 3 week cycle .
Outcome measures
| Measure |
Gemcitabine, Cisplatin and MEK162
n=12 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
MTD of MEK162 - Phase I
|
45 mg
|
PRIMARY outcome
Timeframe: 6 monthsAn exact binomial single stage design will be used to discriminate between true 6-month PFS rates of 59% vs. 82%, and between true response rates of 26% and 50%. 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 |
Gemcitabine, Cisplatin and MEK162
n=42 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
Six-month Progression Free Survival
Progression free
|
19 Participants
|
|
Six-month Progression Free Survival
Progressed
|
23 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: 1 participant withdrew consent before starting treatment
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by 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 |
Gemcitabine, Cisplatin and MEK162
n=41 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
Objective Response Rate (ORR)
|
12 percentage of participants with ORR
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 1 participants withdrew consent before received treatment
progression free survival will be calculated from study entry to documented disease progression or death from any cause, whatever occurs first.
Outcome measures
| Measure |
Gemcitabine, Cisplatin and MEK162
n=41 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
Median PFS
|
6 months
Interval 4.0 to 12.0
|
SECONDARY outcome
Timeframe: 1 yearPopulation: 1 participant withdrew consent before starting treatment
(survival) will be calculated from study entry to death or last follow up
Outcome measures
| Measure |
Gemcitabine, Cisplatin and MEK162
n=41 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
Median Overall Survival
|
13.3 months
Interval 9.8 to 16.5
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: 1 participants withdrew consent before receiving treatment
All toxicities will be rated as per the NCI Common Toxicity Criteria, version 4.
Outcome measures
| Measure |
Gemcitabine, Cisplatin and MEK162
n=42 Participants
Phase I component of the study, a classic 3+3 cohort dose escalation scheme will be used to identify the MTD of MEK162 when administered with gemcitabine at dose 800 mg/m2 and cisplatin given at dose 20 mg/m2 week 2 \& 3 of a 3 week cycle. The final cohort will receive gemcitabine 1000mg/m2 and cisplatin 20mg/m2 week 2 and 3 of a 3 week cycle in combination with MEK162 at the MTD as determined above. In the phase II part of the study, patients will receive MEK162 at the MTD dose plus gemcitabine and cisplatin at the dose level determined acceptable in the phase I portion. In the phase II part of the study, patients will receive MEK162 at 45mg BID plus gemcitabine (800 mg/m2) and cisplatin (20 mg/m2) as determined by the phase I portion.
|
|---|---|
|
Participants Evaluated for Toxicity
Evaluated for toxicity
|
41 Participants
|
|
Participants Evaluated for Toxicity
Not evaluable/withdrew consent before treatment
|
1 Participants
|
Adverse Events
Cohort 1
Serious events: 1 serious events
Other events: 0 other events
Deaths: 2 deaths
Cohort 2
Serious events: 1 serious events
Other events: 0 other events
Deaths: 4 deaths
Cohort 3
Serious events: 3 serious events
Other events: 0 other events
Deaths: 1 deaths
Cohort 4
Serious events: 29 serious events
Other events: 0 other events
Deaths: 16 deaths
Serious adverse events
| Measure |
Cohort 1
n=3 participants at risk
Cohort 1 Phase I, Dose Level 1 - MEK162 25 mg
|
Cohort 2
n=6 participants at risk
Cohort 2 Phase I, Dose Level 2 - MEK162 45mg
|
Cohort 3
n=3 participants at risk
Cohort 3 Phase I, Dose Level 3 / Phase II - MTD mg
|
Cohort 4
n=29 participants at risk
Cohort 4 Phase II only, MTD mg
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
66.7%
2/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
55.2%
16/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
24.1%
7/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
24.1%
7/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
|
Investigations
Neutropenia
|
33.3%
1/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
16.7%
1/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
66.7%
2/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
69.0%
20/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
33.3%
1/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
58.6%
17/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
|
Investigations
Hyperlipasemia
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/6 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
0.00%
0/3 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
24.1%
7/29 • 2 years
SAE's collected. Non-SAE/AE data were not collected.
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Ghassan Abou-Alfa, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4184
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place