mek inhibitor msc1936369b plus folfiri in second line k-ras mutated metastatic colorectal cancer (mcrc)

Conditions: Metastatic Colorectal Cancer

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


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

Keywords: mek inhibitor metastatic colorectal cancer k-ras mutation phase ii second line k-ras mutated metastatic colorectal cancer