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

Merck KGaA (EMD Serono)

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Metastatic Colorectal Cancer

Treatments: Drug: Placebo; Drug: Pimasertib; Drug: FOLFIRI

Study type: Interventional

Funder types: Industry

Identifiers

NCT01085331

EMR200066_004

Details and patient eligibility

About

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

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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16 participants in 3 patient groups

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

Experimental group

Treatment:

Drug: FOLFIRI

Drug: Pimasertib

Part 2 or Phase 2 Randomized part: Pimasertib+FOLFIRI

Experimental group

Description:

Planned, not performed

Treatment:

Drug: FOLFIRI

Drug: Pimasertib

Part 2 or Phase 2 Randomized part: Placebo+FOLFIRI

Experimental group

Description:

Planned, not performed

Treatment:

Drug: FOLFIRI

Drug: Placebo