Clinical Trials /

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

NCT02703571

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
  • Official Title: A Phase I/II Study of Safety and Efficacy of Ribociclib (LEE011) in Combination With Trametinib (TMT212) in Patients With Metastatic or Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CTMT212X2106
  • SECONDARY ID: 2015-005019-34
  • NCT ID: NCT02703571

Conditions

  • Solid Tumors
  • Pancreatic Cancer
  • Colorectal Cancer

Interventions

DrugSynonymsArms
ribociclibLEE011Advanced or metastatic pancreatic cancer
TrametinibTMT212Advanced or metastatic pancreatic cancer

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Advanced or metastatic pancreatic cancerExperimentalPatients in the Phase II portion of the study who have advanced or metastatic pancreatic cancer
  • ribociclib
  • Trametinib
KRAS-mutant colorectal cancerExperimentalPatients in the Phase II portion of the study who have KRAS-mutant colorectal cancer
  • ribociclib
  • Trametinib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:21-day cycle one of treatment
Safety Issue:
Description:Phase I 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

Measure:Duration of response (DOR)
Time Frame:Until progression of disease up to 1 year
Safety Issue:
Description: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.
Measure:Time to response
Time Frame:Until progression of disease up to 1 year
Safety Issue:
Description: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.
Measure:Disease control rate
Time Frame:Until progression of disease up to 1 year
Safety Issue:
Description: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.
Measure:Progression disease rate
Time Frame:Until progression of disease up to 1 year
Safety Issue:
Description:Progression disease rate defined as the proportion of patients with a progression disease as assessed per RECIST 1.1 by investigator assessment.
Measure:Progression free survival
Time Frame:Until progression of disease up to 1 year
Safety Issue:
Description: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.
Measure:overall survival
Time Frame:Until death up to 1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

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

Last Updated