Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03981614|
Recruitment Status : Active, not recruiting
First Posted : June 11, 2019
Last Update Posted : June 16, 2022
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Carcinoma 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)|
|Actual Enrollment :||101 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|
|Actual Study Start Date :||October 29, 2019|
|Actual Primary Completion Date :||August 23, 2021|
|Estimated Study Completion Date :||October 8, 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.
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): NCT03981614
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Kansas|
|Cancer Center of Kansas - Wichita|
|Wichita, Kansas, United States, 67214|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Scott Kopetz||Academic and Community Cancer Research United|