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

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

Upon careful review of all available efficacy and safety data from the study phase Ib part, Novartis decided to not start the study phase II part. This decision was in no means triggered by an unfavorable safety profile of the combination. The observed safety profile of the combination represents contributions of the individual safety profile of trametinib and ribociclib. No new safety signals were observed. The study was closed early in line with protocol Section 4.4.

Intervention public domain (ClinicalTrials.gov)

Drug: ribociclib. Combination treatment with LEE and TMT

Intervention public domain (ClinicalTrials.gov)

Drug: Trametinib. Combination treatment with LEE and TMT

Arm public domain (ClinicalTrials.gov)

Advanced or metastatic solid tumors (experimental): Patients in the Phase I portion of the study who have advanced or metastatic solid tumors

Primary outcome public domain (ClinicalTrials.gov)

Incidence of dose limiting toxicities (DLTs). Phase Ib part: The primary variable is the incidence of DLTs during the first 21 days of therapy. Estimation of the MTD of the combination treatment will be based upon the estimation of the probability of DLT during the first 21 days of therapy for patients in the DDS. Time frame: 21-day cycle one of treatment.

Primary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR). Phase II part: The primary variable used to evaluate the efficacy of the ribociclib and trametinib combination is the ORR, defined as the proportion of patients with a best overall confirmed CR or PR, as assessed per RECIST 1.1 by investigator assessment. Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of response (DOR). Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Time to response. Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Disease control rate. Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Progression disease rate. Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

Progression free survival. Time frame: Until progression of disease up to 1 year.

Secondary outcome public domain (ClinicalTrials.gov)

overall survival. Time frame: Until death up to 1 year.

Eligibility public domain (ClinicalTrials.gov)

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 …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 95 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Company decision