Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
- Conditions
- Solid Tumors for Phase IbPancreatic Cancer for Phase IIColorectal Cancer for Phase II
- Interventions
- Registration Number
- NCT02703571
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 95
Not provided
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Advanced or metastatic solid tumors Trametinib Patients in the Phase I portion of the study who have advanced or metastatic solid tumors Advanced or metastatic solid tumors ribociclib Patients in the Phase I portion of the study who have advanced or metastatic solid tumors
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Until progression of disease up to 1 year 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.Incidence of dose limiting toxicities (DLTs) 21-day cycle one of treatment 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.
- Secondary Outcome Measures
Name Time Method Disease control rate Until progression of disease up to 1 year Phase II part:
Disease control rate (DCR) is defined as the proportion of patients with best overall response of CR, PR, or SD per RECIST 1.1. DCR will be estimated and the binomial exact 95% CI will be provided by arm.Progression disease rate Until progression of disease up to 1 year Phase Ib part:
Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.Progression free survival Until progression of disease up to 1 year Phase Ib and phase II parts:
Progression-free survival (PFS) is defined as the time from the date of the first dose of study drug to the date of first documented disease progression per RECIST 1.1 or death due to any cause.Time to response Until progression of disease up to 1 year Phase II part:
Time to overall response of CR or PR (TTR) is defined as the time from start of study drug to first documented response (CR or PR, which must be confirmed subsequently) for patients with a confirmed CR or PR. TTR will be summarized by treatment arm, using descriptive statistics.overall survival Until death up to 1 year Phase Ib and phase II parts:
Overall survival (OS) is defined as the time from the date of first dose of study drug to the date of death due to any cause.Duration of response (DOR) Until progression of disease up to 1 year Phase II part:
Among patients with a confirmed response (PR or CR) per RECIST 1.1, DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause. The distribution function of DOR will be estimated using the Kaplan-Meier method. The median DOR along with 95% CI will be presented by treatment arm.
Trial Locations
- Locations (7)
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Dana Farber Cancer Center
🇺🇸Boston, Massachusetts, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of Miami Sylvester Comp Cancer Ctr
🇺🇸Miami, Florida, United States
UT MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Novartis Investigative Site
🇪🇸Barcelona, Catalunya, Spain