Patient case: 61-year-old male with Ampullary carcinoma. Genetic variant: KRAS. Other conditions: None.

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

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: 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

Relevance to patient case: not relevant