MEK Inhibitor MSC1936369B Plus FOLFIRI in Second Line K-Ras Mutated Metastatic Colorectal Cancer (mCRC)

NCT ID: NCT01085331

Last Updated: 2016-10-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2012-04-30

Brief Summary

The research trial is testing the experimental treatment pimasertib (MSC1936369B) in combination with FOLFIRI, as second-line treatment in metastatic K Ras mutated colorectal cancer subjects. The study will be run in two parts:

Part 1, or Safety Run-in Part: Will determine the maximum tolerated dose and the recommended Phase 2 dose (RP2D) of pimasertib combined with FOLFIRI as second-line treatment in subjects with metastatic K Ras mutated colorectal cancer.

Part 2 or Phase 2 Randomised Part: Will assess the anti-tumor activity of pimasertib combined with FOLFIRI compared to FOLFIRI with placebo as second-line treatment in metastatic K Ras mutated colorectal cancer subjects.

Phase I which Is an open label dose escalation "3+3" cohort, non-randomized, safety Phase II which is a double blind randomized safety/efficacy

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1 or Safety Run-in Part: Pimasertib+FOLFIRI

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

FOLFIRI

Intervention Type: DRUG

Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter \[mg/m\^2\] intravenous \[i.v\] infusion over 90 minutes or leucovorin \[dl-leucovorin\] 400 mg/m\^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m\^2 given as a 90-minute infusion in 500 milliliter \[mL\] dextrose 5%; followed by a bolus 5-fluorouracil \[FU\] 400 mg/m\^2 and a 46-hour infusion 5-FU 2400 mg/m\^2) at conventional doses on days 1 and 15 of the same 28 day cycle.

Part 2 or Phase 2 Randomized part: Pimasertib+FOLFIRI

Planned, not performed

Group Type: EXPERIMENTAL

Pimasertib

Intervention Type: DRUG

Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

FOLFIRI

Intervention Type: DRUG

Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter \[mg/m\^2\] intravenous \[i.v\] infusion over 90 minutes or leucovorin \[dl-leucovorin\] 400 mg/m\^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m\^2 given as a 90-minute infusion in 500 milliliter \[mL\] dextrose 5%; followed by a bolus 5-fluorouracil \[FU\] 400 mg/m\^2 and a 46-hour infusion 5-FU 2400 mg/m\^2) at conventional doses on days 1 and 15 of the same 28 day cycle.

Part 2 or Phase 2 Randomized part: Placebo+FOLFIRI

Planned, not performed

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Subjects will be administered with placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

FOLFIRI

Intervention Type: DRUG

Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter \[mg/m\^2\] intravenous \[i.v\] infusion over 90 minutes or leucovorin \[dl-leucovorin\] 400 mg/m\^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m\^2 given as a 90-minute infusion in 500 milliliter \[mL\] dextrose 5%; followed by a bolus 5-fluorouracil \[FU\] 400 mg/m\^2 and a 46-hour infusion 5-FU 2400 mg/m\^2) at conventional doses on days 1 and 15 of the same 28 day cycle.

Interventions

Pimasertib

Subjects will be administered with pimasertib orally once daily on Days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

Intervention Type: DRUG

Placebo

Subjects will be administered with placebo orally once daily on days 1-5, 8-12, 15-19, and 22-26 of a 28 day cycle.

Intervention Type: DRUG

FOLFIRI

Subjects will be administered with FOLFIRI (laevoleucovorin 200 milligram per square meter \[mg/m\^2\] intravenous \[i.v\] infusion over 90 minutes or leucovorin \[dl-leucovorin\] 400 mg/m\^2 i.v. infusion over 90 minutes; followed by irinotecan 180 mg/m\^2 given as a 90-minute infusion in 500 milliliter \[mL\] dextrose 5%; followed by a bolus 5-fluorouracil \[FU\] 400 mg/m\^2 and a 46-hour infusion 5-FU 2400 mg/m\^2) at conventional doses on days 1 and 15 of the same 28 day cycle.

Intervention Type: DRUG

Other Intervention Names

MSC1936369B

Eligibility Criteria

Inclusion Criteria

For Safety Run-in and Part 2 or Phase 2 Randomised Part

• Histologically confirmed K-Ras mutated colon/rectum cancer
• Subject's disease must have progressed during or after a first-line treatment for metastatic disease with oxaliplatin and fluoropyrimidines based chemotherapy with or without bevacizumab
• Evidence of metastatic measurable disease at trial entry as per Response Evaluation Criteria in Solid Tumors. Complete tumor assessment performed within 14 days prior to first trial drug administration
• Male/female subjects aged greater than or equal to (>=) 18 years
• Subject has read and understood the informed consent form
• Women of childbearing potential must have a negative blood pregnancy test at the screening visit. Subjects and their partners must be willing to avoid pregnancy during the trial

Exclusion Criteria

For Safety Run-in and Part 2 or Phase 2 Randomised Part

• Bone marrow impairment
• Renal impairment
• Liver function and liver cell integrity abnormality
• History of central nervous system (CNS) metastases
• History of difficulty of swallowing, malabsorption or other chronic gastrointestinal disease
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) greater than (>)1
• Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B
• Has received extensive prior radiotherapy on more than 30 percent (%) of bone marrow reserves, or prior bone marrow/stem cell transplantation
• Has received chemotherapy, any investigational drug, or having participated in another clinical trial within the past 4 weeks prior to trial first drug administration
• Has a history of any other significant medical disease
• Past or current history (within the last 2 years prior to inclusion) of malignancies except for the indication under this study
• Has significant cardiac conduction abnormalities and/or pacemaker
• Is a pregnant or nursing female
• Has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion
• Other significant disease that in the Investigator's opinion would exclude the subject from the trial
• Known hypersensitivity to the trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s)
• Legal incapacity or limited legal capacity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Serono S.A., Geneva

Locations

Research Site

Leuven, , Belgium

Research Site

Napoli, , Italy

Research Site

Barcelona, , Spain

Countries

Belgium; Italy; Spain

Other Identifiers

EMR200066_004

Identifier Type: -

Identifier Source: org_study_id