Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors

• Status: Terminated
• Trial end date: 2019-09-24
• Target enrollment: 0
• Participant gender: All

Summary

Phase Ib dose escalation in advanced solid tumors to identify dose for Phase II dose expansion in advanced or metastatic pancreatic cancer and KRAS-mutant colorectal cancer. Open-label, nonrandomized.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Trametinib

Criteria

Inclusion Criteria (All):

• Written informed consent must

• Patient has histologically and/or cytologically confirmed malignancies:

Phase I:

• Patients with advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available;

Phase II:

• Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic antineoplastic therapies in the advanced setting

• Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies in the advanced setting without a standard of care treatment option available. Testing for KRAS mutation in patients with CRC using locally approved diagnostic kit will be used for eligibility.

• Phase II only: patient must have measurable disease

• Patient has an ECOG performance status 0 or 1.

• Patient has adequate bone marrow and organ function

• Patient must have specified laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication on Cycle 1 Day 1:

• Standard 12-lead ECG values defined

Exclusion Criteria:

Phase II only:

• Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.

Phase I and Phase II:

• Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.

• Patient is concurrently using other anti-cancer therapy.

• Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1

• Patient has received local therapy to liver ≤ 3 months of C1D1

• History of liver disease as follow:

• Cirrhosis

• Autoimmune hepatitis

• Active viral hepatitis

• Portal hypertension

• Drug induced liver steatosis

• Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1

• Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin.

• Patient is currently receiving warfarin or other coumadin derived anti-coagulant

• Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months of screening.

• Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day 1, with the exception of adequately treated basal or squamous cell carcinoma or curatively resected cervical cancer.

• Patients with central nervous system (CNS) involvement

• Patient has impairment of GI function or GI disease that may significantly alter the absorption of the study drugs

• History of interstitial lung disease or pneumonitis.

• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality

• Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or Substances that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:

• Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.

• History of retinal vein occlusion (RVO)

Other protocol-defined inclusion/exclusion criteria may apply.