Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03981614|
Recruitment Status : Not yet recruiting
First Posted : June 11, 2019
Last Update Posted : June 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|KRAS Gene Mutation Metastatic Colorectal Carcinoma NRAS Gene Mutation Stage III Colorectal Cancer AJCC v8 Stage IIIA Colorectal Neuroendocrine Tumor AJCC v8 Stage IIIB Colorectal Cancer AJCC v8 Stage IIIC Colorectal Cancer AJCC v8 Stage IV Colorectal Cancer AJCC v8 Stage IVA Colorectal Cancer AJCC v8 Stage IVB Colorectal Cancer AJCC v8 Stage IVC Colorectal Cancer AJCC v8 Unresectable Carcinoma||Drug: Binimetinib Drug: Palbociclib Drug: Trifluridine and Tipiracil Hydrochloride||Phase 2|
I. The primary objective is to compare the progression-free survival (PFS) between those randomized to palbociclib/binimetinib and those randomized to trifluridine and tipiracil hydrochloride (TAS-102) in patients with refractory KRAS- or NRAS-mutant metastatic colorectal cancer (CRC).
I. To compare the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria between those randomized to palbociclib/binimetinib and those randomized to TAS-102 in patients with refractory KRAS- or NRAS-mutant metastatic CRC.
II. To compare the overall survival (OS) between those randomized to palbociclib/binimetinib and those randomized to TAS-102 in patients with refractory KRAS- or NRAS-mutant metastatic CRC.
III. To determine the safety and tolerability of the recommended phase II dose of palbociclib in combination with binimetinib in patients with refractory KRAS- or NRAS-mutant metastatic CRC.
CORRELATIVE RESEARCH OBJECTIVES:
I. To determine the tumor mutational profiles that characterize groups of patients that predict for response or resistance to combination of palbociclib/binimetinib.
II. To determine the correlation between circulating tumor deoxyribonucleic acid (DNA) and tumor response or resistance to therapy with palbociclib/binimetinib or TAS-102.
III. To determine the association between Consensus Molecular Subtype based on gene expression profiling and response or resistance to combination of palbociclib/binimetinib.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28 and palbociclib PO once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-12. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with disease progression may optionally crossover to Arm A.
After completion of study treatment, patients are followed up within 30-37 days and then every 12 weeks for up to 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||112 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Combination of MEK Inhibitor Binimetinib and CDK4/6 Inhibitor Palbociclib in KRAS and NRAS Mutant Metastatic Colorectal Cancers|
|Estimated Study Start Date :||June 28, 2019|
|Estimated Primary Completion Date :||December 28, 2020|
|Estimated Study Completion Date :||December 28, 2022|
Experimental: Arm A (binimetinib, palbociclib)
Patients receive binimetinib PO BID on days 1-28 and palbociclib PO QD on days 1-21. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Experimental: Arm B (trifluridine and tipiracil hydrochloride)
Patients receive trifluridine and tipiracil hydrochloride PO BID on days 1-5 and 8-12. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients with disease progression may optionally crossover to Arm A.
Drug: Trifluridine and Tipiracil Hydrochloride
- Progression free survival (PFS) [ Time Frame: Time from randomization date to either disease progression or death from any cause, whichever occurs first, assessed for up to 24 months ]Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and will be documented at each enrolling site with no central review planned. PFS will be compared between treatment arms using the stratified log rank test at one-sided level 0.05. Kaplan-Meier methodology will be used to estimate the median PFS for each treatment arm, and Kaplan-Meier curves will be produced.
- Overall response rate [ Time Frame: Up to 24 months ]Assessment of response data will be performed on the basis of definitions of responses according to RECIST version (v)1.1. Objective response is defined as a complete or partial response by RECIST v1.1. This will be reported as a proportion with a 95% confidence interval for the true proportion.
- Overall survival (OS) [ Time Frame: Time from first dose of study treatment to death from any cause, assessed for up to 24 months ]Will use Kaplan-Meier methods to evaluate time to event endpoints, and will report median OS and its 95% confidence interval.
- Incidence of adverse events [ Time Frame: Up to 24 months ]Adverse events (AEs) will be described by grade for grade 1 and above with and without attribution considered. The maximum grade for each type of adverse event will be recorded for each patient, and described using frequency tables. The adverse events will be compared by arm to determine any differences. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03981614
|United States, Arizona|
|Mayo Clinic in Arizona||Not yet recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Laurie A. Mihalik 480-342-3256 email@example.com|
|Principal Investigator: Tanios S. Bekaii-Saab|
|United States, California|
|City of Hope Comprehensive Cancer Center||Not yet recruiting|
|Duarte, California, United States, 91010|
|Contact: Marwan G. Fakih 626-256-4673 firstname.lastname@example.org|
|Principal Investigator: Marwan G. Fakih|
|United States, Florida|
|Cleveland Clinic-Weston||Not yet recruiting|
|Weston, Florida, United States, 33331|
|Contact: Sharon Lew Lews2@ccf.org|
|Principal Investigator: Zeina A. Nahleh|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Christina S. Wu 404-778-0202 email@example.com|
|Principal Investigator: Christina S. Wu|
|United States, Kansas|
|University of Kansas Cancer Center||Not yet recruiting|
|Kansas City, Kansas, United States, 66160|
|Contact: Amanda Ho 316-613-4326 firstname.lastname@example.org|
|Principal Investigator: Shaker R. Dakhil|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Not yet recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Michele Vincitore 617-632-3125 email@example.com|
|Principal Investigator: Kimmie Ng|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center||Not yet recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Catherine A. Griffin 919-962-2621 firstname.lastname@example.org|
|Principal Investigator: Michael S. Lee|
|United States, Texas|
|M D Anderson Cancer Center||Not yet recruiting|
|Houston, Texas, United States, 77030|
|Contact: Scott Kopetz 507-266-0800 email@example.com|
|Principal Investigator: Scott Kopetz|
|Principal Investigator:||Scott Kopetz||Academic and Community Cancer Research United|