Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors
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ClinicalTrials.gov Identifier: NCT02703571 |
Recruitment Status :
Terminated
(Company decision)
First Posted : March 9, 2016
Last Update Posted : December 21, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Solid Tumors for Phase Ib Pancreatic Cancer for Phase II Colorectal Cancer for Phase II | Drug: ribociclib Drug: Trametinib | Phase 1 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 95 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | single group for phase 1b parallel group for phase 2 |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | June 29, 2016 |
Actual Primary Completion Date : | September 24, 2019 |
Actual Study Completion Date : | September 24, 2019 |

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
Other Name: LEE011 Drug: Trametinib Combination treatment with LEE and TMT
Other Name: TMT212 |
- Incidence of dose limiting toxicities (DLTs) [ Time Frame: 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.
- Objective Response Rate (ORR) [ Time Frame: 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.
- Duration of response (DOR) [ Time Frame: 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.
- Time to response [ Time Frame: 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.
- Disease control rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
- overall survival [ Time Frame: 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02703571
United States, Arkansas | |
Highlands Oncology Group | |
Fayetteville, Arkansas, United States, 72703 | |
United States, California | |
City of Hope National Medical Center | |
Duarte, California, United States, 91010 | |
United States, Connecticut | |
Yale University School of Medicine | |
New Haven, Connecticut, United States, 06520 | |
United States, Florida | |
University of Miami Sylvester Comp Cancer Ctr | |
Miami, Florida, United States, 33136 | |
United States, Massachusetts | |
Dana Farber Cancer Center | |
Boston, Massachusetts, United States, 02215 | |
United States, Texas | |
UT MD Anderson Cancer Center | |
Houston, Texas, United States, 77030 | |
Australia, Victoria | |
Novartis Investigative Site | |
Melbourne, Victoria, Australia, 3000 | |
Belgium | |
Novartis Investigative Site | |
Leuven, Belgium, 3000 | |
Canada, Alberta | |
Novartis Investigative Site | |
Edmonton, Alberta, Canada, T6G 1Z2 | |
Canada, British Columbia | |
Novartis Investigative Site | |
Vancouver, British Columbia, Canada, V5Z 4E6 | |
Germany | |
Novartis Investigative Site | |
Koeln, Germany, 50937 | |
Novartis Investigative Site | |
Ulm, Germany, 89081 | |
Netherlands | |
Novartis Investigative Site | |
Amsterdam, Netherlands, 1066 CX | |
Novartis Investigative Site | |
Utrecht, Netherlands, 3584 CX | |
Spain | |
Novartis Investigative Site | |
Barcelona, Catalunya, Spain, 08035 |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02703571 |
Other Study ID Numbers: |
CTMT212X2106 2015-005019-34 ( EudraCT Number ) |
First Posted: | March 9, 2016 Key Record Dates |
Last Update Posted: | December 21, 2020 |
Last Verified: | September 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Plan Description: | Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Trametinib Ribociclib LEE011 TMT212 advanced solid tumors |
pancreatic cancer KRAS-mutant colorectal cancer colorectal cancer advanced pancreatic cancer metastatic pancreatic cancer |
Colorectal Neoplasms Pancreatic Neoplasms Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases |
Intestinal Diseases Rectal Diseases Endocrine Gland Neoplasms Pancreatic Diseases Endocrine System Diseases Trametinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |