Study Of Safety And Efficacy Of Ribociclib And Trametinib In Patients With Metastatic Or Advanced Solid Tumors

Study Overview

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

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.

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.

Solid Tumors for Phase Ib
Pancreatic Cancer for Phase II
Colorectal Cancer for Phase II

DRUG: ribociclib
DRUG: Trametinib

CTMT212X2106
2015-005019-34 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-03-04	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2020-12-17
First Submitted that Met QC Criteria 2016-03-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2020-12-21
First Posted (ACTUAL) 2016-03-09	Results First Posted N/A	Last Verified 2020-09

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Advanced or metastatic solid tumors Patients in the Phase I portion of the study who have advanced or metastatic solid tumors	DRUG: ribociclib Combination treatment with LEE and TMT DRUG: Trametinib Combination treatment with LEE and TMT

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Advanced or metastatic solid tumors

Patients in the Phase I portion of the study who have advanced or metastatic solid tumors

DRUG: ribociclib

Combination treatment with LEE and TMT

DRUG: Trametinib

Combination treatment with LEE and TMT

Primary Outcome Measures	Measure Description	Time Frame
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.	21-day cycle one of treatment
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.	Until progression of disease up to 1 year

Secondary Outcome Measures	Measure Description	Time Frame
Duration of response (DOR)	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.	Until progression of disease up to 1 year
Time to response	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.	Until progression of disease up to 1 year
Disease control rate	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.	Until progression of disease up to 1 year
Progression disease rate	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.	Until progression of disease up to 1 year
Progression free survival	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.	Until progression of disease up to 1 year
overall survival	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.	Until death up to 1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Written informed consent must
Patient has histologically and/or cytologically confirmed malignancies:

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record