Study of Trametinib and Ruxolitinib in Colorectal Cancer and Pancreatic Adenocarcinoma

This is an interventional treatment trial for Colorectal Cancer Read More

Inclusion Criteria:

• Patients (male or female) ≥ 21.
• Patients with histological diagnosis of RAS mutant advanced colorectal and pancreatic adenocarcinoma having received at least 1 prior line of systemic therapy. Pancreatic cancer patients with KRAS mutation detected on plasma profiling having received at least 1 prior line of systemic therapy.
• Patients must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria version 1.1.
• Life expectancy of at least 3 months.
• Written informed consent that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.

• Have adequate organ and hematologic function, as determined by:

  • Absolute neutrophil count (ANC) ≥ 1,500/μl.
  • Platelets ≥ 100,000/μl.
  • Haemoglobin ≥ 9g/dL.
  • Aspartate Amino Transferase (AST)/ Alanine Amino Transferase (ALT) ≤ 2.5 x upper limit of normal (ULN ≤ 5 x ULN is acceptable if liver metastases are present).
  • Total bilirubin ≤1.5 x ULN (< 3 ULN for patients with Gilbert syndrome).
  • Creatinine clearance ≥ 60ml/min.
  • Prothrombin time and activated partial thromboplastin time ≤ 1.5 x upper limit of normal (ULN) per institutional laboratory normal range.
  • Ejection fraction ≥ 50% with no symptoms attributable to heart failure.
• Have normal QT interval on screening electrocardiogram (ECG) evaluation, defined as QT interval corrected (Fridericia) (QTcF) of ≤450 ms in males or ≤470 ms in females.
• For female patients of childbearing potential, a negative pregnancy test must be documented prior to enrolment.
• Female and male patients who are fertile must agree to use a highly effective form of contraception with their sexual partners throughout study participation.
• Have the willingness and ability to comply with scheduled visits and study procedures.

Exclusion Criteria:

• Received cytotoxic chemotherapy, investigational agents, or radiation within 14 days of study drug commencement, or 5 half-lives, whichever is shorter, and with recovery of clinically significant toxicities from that therapy.
• Received monoclonal antibodies or had surgery within 30 days of the first dose of study drug.
• Have been diagnosed with another primary malignancy within the past 3 years of study drug commencement (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer).
• Have CNS metastases that are symptomatic, neurologically unstable, or requiring an increasing dose of corticosteroids.
• Have meningeal involvement or spinal cord compression.

• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:

  • Myocardial infarction (MI) within 6 months prior to the first dose.
  • Unstable angina within 6 months prior to first dose.
  • History of congestive heart failure (CHF).
  • History of clinically significant atrial arrhythmia.
  • Any history of ventricular arrhythmia.
  • Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose.
• Have history or the presence of pulmonary interstitial disease or drug related pneumonitis.
• Have an ongoing or active infection.
• Patients with active HBV and HCV are excluded unless they are undergoing treatment for HBV and HCV.
• Have a history of or active significant gastrointestinal (GI) bleeding within 3 months of the first dose.
• Patients who are on immunosuppressive therapy.
• Patients who have retinal vein occlusion and retinal pigment epithelial detachment.
• On medications which are potent and moderate inhibitor and inducers of CYP3A4.
• Patients with moderate to severe hepatic impairment (Child Pugh B and C).
• Patients with history of severe allergic skin reactions or current skin conditions.