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

NCT ID: NCT02703571

Last Updated: 2020-12-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

95 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-29

Study Completion Date

2019-09-24

Brief Summary

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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

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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.

Conditions

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

Keywords

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Trametinib Ribociclib LEE011 TMT212 advanced solid tumors pancreatic cancer KRAS-mutant colorectal cancer colorectal cancer advanced pancreatic cancer metastatic pancreatic cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

single group for phase 1b parallel group for phase 2
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Advanced or metastatic solid tumors

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

Group Type EXPERIMENTAL

ribociclib

Intervention Type DRUG

Combination treatment with LEE and TMT

Trametinib

Intervention Type DRUG

Combination treatment with LEE and TMT

Interventions

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ribociclib

Combination treatment with LEE and TMT

Intervention Type DRUG

Trametinib

Combination treatment with LEE and TMT

Intervention Type DRUG

Other Intervention Names

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LEE011 TMT212

Eligibility Criteria

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Inclusion Criteria

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

City of Hope National Medical Center

Duarte, California, United States

Site Status

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status

University of Miami Sylvester Comp Cancer Ctr

Miami, Florida, United States

Site Status

Dana Farber Cancer Center

Boston, Massachusetts, United States

Site Status

UT MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Edmonton, Alberta, Canada

Site Status

Novartis Investigative Site

Vancouver, British Columbia, Canada

Site Status

Novartis Investigative Site

Cologne, , Germany

Site Status

Novartis Investigative Site

Ulm, , Germany

Site Status

Novartis Investigative Site

Amsterdam, , Netherlands

Site Status

Novartis Investigative Site

Utrecht, , Netherlands

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Countries

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United States Australia Belgium Canada Germany Netherlands Spain

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17721

Results for CTMT212X2106 from the Novartis Clinical Trials Website

Other Identifiers

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2015-005019-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTMT212X2106

Identifier Type: -

Identifier Source: org_study_id