Trial Outcomes & Findings for MK-0646 and Gemcitabine +/- Erlotinib for Patients With Advanced Pancreatic Cancer (NCT NCT00769483)
NCT ID: NCT00769483
Last Updated: 2020-09-03
Results Overview
MK-0646 10 mg/kg was declared to be the MTD in combination with gemcitabine and 5 mg/kg the MTD in combination with Gemcitabine and erlotinib
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
81 participants
Primary outcome timeframe
up to 12 cycles
Results posted on
2020-09-03
Participant Flow
Completed, last patient enrolled in September 26th, 2013
Participant milestones
| Measure |
Arm A / Phase I
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
9
|
13
|
15
|
15
|
16
|
9
|
|
Overall Study
COMPLETED
|
9
|
12
|
15
|
15
|
15
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Arm A / Phase I
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
1
|
0
|
Baseline Characteristics
MK-0646 and Gemcitabine +/- Erlotinib for Patients With Advanced Pancreatic Cancer
Baseline characteristics by cohort
| Measure |
Arm A / Phase I
n=9 Participants
Arm A: MK-0646 (MK) + gemcitabine(G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22. .
|
Arm B / Phase I
n=12 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 Participants
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 Participants
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
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=8 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
42 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
33 Participants
n=8 Participants
|
|
Age, Continuous
|
63.56 years
STANDARD_DEVIATION 7.21 • n=5 Participants
|
63.33 years
STANDARD_DEVIATION 12.57 • n=7 Participants
|
62.33 years
STANDARD_DEVIATION 7.66 • n=5 Participants
|
62.27 years
STANDARD_DEVIATION 7.62 • n=4 Participants
|
67.8 years
STANDARD_DEVIATION 8.41 • n=21 Participants
|
60.89 years
STANDARD_DEVIATION 9.43 • n=8 Participants
|
63.5 years
STANDARD_DEVIATION 8.9 • n=8 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
28 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
47 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
69 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
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=8 Participants
|
2 Participants
n=8 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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
4 Participants
n=8 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=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
61 Participants
n=8 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
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
12 participants
n=7 Participants
|
15 participants
n=5 Participants
|
15 participants
n=4 Participants
|
15 participants
n=21 Participants
|
9 participants
n=8 Participants
|
75 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: up to 12 cyclesPopulation: The primary endpoint is MTD which was analyzed based on phase I participants only. Phase II (Arms A and B) or phase II expansion participants were not included in the analysis per design.
MK-0646 10 mg/kg was declared to be the MTD in combination with gemcitabine and 5 mg/kg the MTD in combination with Gemcitabine and erlotinib
Outcome measures
| Measure |
Arm A / Phase I
n=9 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
n=12 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
MK-0646 Maximum Tolerable Dose
MK 5mg +G: #DLT
|
0 participants
|
0 participants
|
—
|
—
|
—
|
—
|
|
MK-0646 Maximum Tolerable Dose
MK 10mg +G: # DLT
|
0 participants
|
2 participants
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 monthsPopulation: For any group that was not analyzed for Progression Free Survival (PFS) outcome the number of participants has been set to be zero.
Time interval (in months) from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Outcome measures
| Measure |
Arm A / Phase I
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 Participants
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 Participants
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Progression Free Survival
|
—
|
—
|
1.8 months
Interval 1.8 to 9.7
|
1.8 months
Interval 1.7 to 5.5
|
1.9 months
Interval 1.8 to 5.4
|
2.0 months
Interval 1.8 to
Not estimable for the upper bound of the 95% CI
|
SECONDARY outcome
Timeframe: From date of randomization until the date of death from any cause, assessed up to 100 monthsPopulation: For any group that was not analyzed for Overall Survival (OS) outcome the number of participants has been set to be zero.
Time interval (in months) from date of randomization until the date of death from any cause
Outcome measures
| Measure |
Arm A / Phase I
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 Participants
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 Participants
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Overall Survival
|
—
|
—
|
10.4 months
Interval 3.9 to 18.9
|
7.1 months
Interval 5.2 to 20.0
|
5.7 months
Interval 4.0 to 9.5
|
8.2 months
Interval 5.3 to
Not estimable for the upper bound of the 95% CI
|
SECONDARY outcome
Timeframe: From start of the treatment until disease progression/recurrence; or through study completion (average of 1 year)Population: For any group that was not analyzed for Overall Response Rate outcome the number of participants has been set to be zero.
Complete response + Partial response using RECIST (Response Evaluation Criteria in Solid Tumors)
Outcome measures
| Measure |
Arm A / Phase I
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 Participants
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 Participants
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Overall Response Rate
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Through the treatment cyclesNumber of patients who developed toxicity from treatment according to the National Cancer Institute's Common Terminology Criteria
Outcome measures
| Measure |
Arm A / Phase I
n=9 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
n=12 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 Participants
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 Participants
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 Participants
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 Participants
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Treatment Toxicity
|
9 Participants
|
12 Participants
|
15 Participants
|
15 Participants
|
15 Participants
|
9 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: After completing treatmentIGF1 expression in tissue was measured and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: After completing treatmentIGF1 expression in plasma was measured in patients and correlated with 1 year patients survival. Inadequate biopsy data for outcome measure.
Outcome measures
Outcome data not reported
Adverse Events
Arm A / Phase I
Serious events: 0 serious events
Other events: 9 other events
Deaths: 9 deaths
Arm B / Phase I
Serious events: 2 serious events
Other events: 12 other events
Deaths: 12 deaths
Arm A / Phase II Randomization
Serious events: 2 serious events
Other events: 15 other events
Deaths: 15 deaths
Arm B / Phase II Randomization
Serious events: 4 serious events
Other events: 15 other events
Deaths: 15 deaths
Arm C / Phase II Randomization
Serious events: 1 serious events
Other events: 12 other events
Deaths: 15 deaths
Phase II Expansion
Serious events: 1 serious events
Other events: 9 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
Arm A / Phase I
n=9 participants at risk
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
n=12 participants at risk
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 participants at risk
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 participants at risk
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 participants at risk
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 participants at risk
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
G4 thrombocytopenia
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Blood and lymphatic system disorders
G4 neutropenia for ≥7 days
|
0.00%
0/9 • assessed up to 100 months
|
16.7%
2/12 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
26.7%
4/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
11.1%
1/9 • assessed up to 100 months
|
Other adverse events
| Measure |
Arm A / Phase I
n=9 participants at risk
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm B / Phase I
n=12 participants at risk
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: intravenously at two dose levels: 5 mg/kg (level I) or 10 mg/kg (level II) on D1,8,15,22.
|
Arm A / Phase II Randomization
n=15 participants at risk
Arm A: MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
Arm B / Phase II Randomization
n=15 participants at risk
Arm B: MK-0646 (MK) + gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily MK dose: 5 mg/kg
|
Arm C / Phase II Randomization
n=15 participants at risk
Arm C: gemcitabine (G) + Erolotinib (E) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle E dose: 100 mg orally daily
|
Phase II Expansion
n=9 participants at risk
MK-0646 (MK) + gemcitabine (G) G dose: 1000 mg/m2 over 100 min on D1,8,15 of a 28-day cycle MK dose: 10 mg/kg
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
77.8%
7/9 • assessed up to 100 months
|
41.7%
5/12 • assessed up to 100 months
|
46.7%
7/15 • assessed up to 100 months
|
26.7%
4/15 • assessed up to 100 months
|
60.0%
9/15 • assessed up to 100 months
|
11.1%
1/9 • assessed up to 100 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
100.0%
9/9 • assessed up to 100 months
|
83.3%
10/12 • assessed up to 100 months
|
40.0%
6/15 • assessed up to 100 months
|
26.7%
4/15 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
100.0%
9/9 • assessed up to 100 months
|
66.7%
8/12 • assessed up to 100 months
|
40.0%
6/15 • assessed up to 100 months
|
46.7%
7/15 • assessed up to 100 months
|
60.0%
9/15 • assessed up to 100 months
|
44.4%
4/9 • assessed up to 100 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
100.0%
9/9 • assessed up to 100 months
|
58.3%
7/12 • assessed up to 100 months
|
60.0%
9/15 • assessed up to 100 months
|
53.3%
8/15 • assessed up to 100 months
|
73.3%
11/15 • assessed up to 100 months
|
77.8%
7/9 • assessed up to 100 months
|
|
Blood and lymphatic system disorders
Lymphopenia
|
77.8%
7/9 • assessed up to 100 months
|
25.0%
3/12 • assessed up to 100 months
|
20.0%
3/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
20.0%
3/15 • assessed up to 100 months
|
11.1%
1/9 • assessed up to 100 months
|
|
General disorders
Fatigue
|
66.7%
6/9 • assessed up to 100 months
|
83.3%
10/12 • assessed up to 100 months
|
40.0%
6/15 • assessed up to 100 months
|
26.7%
4/15 • assessed up to 100 months
|
46.7%
7/15 • assessed up to 100 months
|
88.9%
8/9 • assessed up to 100 months
|
|
Hepatobiliary disorders
Elevated ALK
|
33.3%
3/9 • assessed up to 100 months
|
25.0%
3/12 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Hepatobiliary disorders
Elevated ALT
|
44.4%
4/9 • assessed up to 100 months
|
50.0%
6/12 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
20.0%
3/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
33.3%
3/9 • assessed up to 100 months
|
|
Hepatobiliary disorders
Elevated AST
|
55.6%
5/9 • assessed up to 100 months
|
41.7%
5/12 • assessed up to 100 months
|
40.0%
6/15 • assessed up to 100 months
|
40.0%
6/15 • assessed up to 100 months
|
20.0%
3/15 • assessed up to 100 months
|
22.2%
2/9 • assessed up to 100 months
|
|
Investigations
Elevated INR
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Investigations
Hyperkalemia
|
11.1%
1/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Investigations
Hyponatremia
|
22.2%
2/9 • assessed up to 100 months
|
25.0%
3/12 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Cardiac disorders
Other cardiac toxicity
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Endocrine disorders
Hyperglycemia
|
77.8%
7/9 • assessed up to 100 months
|
50.0%
6/12 • assessed up to 100 months
|
53.3%
8/15 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
22.2%
2/9 • assessed up to 100 months
|
|
Gastrointestinal disorders
Anorexia
|
33.3%
3/9 • assessed up to 100 months
|
50.0%
6/12 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
26.7%
4/15 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
11.1%
1/9 • assessed up to 100 months
|
|
Gastrointestinal disorders
Nausea
|
44.4%
4/9 • assessed up to 100 months
|
58.3%
7/12 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
20.0%
3/15 • assessed up to 100 months
|
46.7%
7/15 • assessed up to 100 months
|
44.4%
4/9 • assessed up to 100 months
|
|
Gastrointestinal disorders
GIT hemorrhage
|
11.1%
1/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Gastrointestinal disorders
Diarrhea
|
44.4%
4/9 • assessed up to 100 months
|
50.0%
6/12 • assessed up to 100 months
|
6.7%
1/15 • assessed up to 100 months
|
46.7%
7/15 • assessed up to 100 months
|
33.3%
5/15 • assessed up to 100 months
|
11.1%
1/9 • assessed up to 100 months
|
|
Vascular disorders
Thrombosis
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Vascular disorders
Pulmonary embolism
|
0.00%
0/9 • assessed up to 100 months
|
0.00%
0/12 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
13.3%
2/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
|
Infections and infestations
Infection
|
11.1%
1/9 • assessed up to 100 months
|
8.3%
1/12 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/15 • assessed up to 100 months
|
0.00%
0/9 • assessed up to 100 months
|
Additional Information
Milind Javle, MD/Professor, GI Medical Oncology
UT MD Anderson Cancer Center
Phone: 713-792-2828
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place