Condition or disease | Intervention/treatment | Phase |
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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 |
PRIMARY OBJECTIVES:
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).
SECONDARY OBJECTIVES:
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 |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Estimated Primary Completion Date : | December 28, 2022 |
Estimated Study Completion Date : | December 28, 2025 |
Arm | Intervention/treatment |
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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.
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Drug: Binimetinib
Given PO
Other Names:
Drug: Palbociclib Given PO
Other Names:
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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.
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Drug: Trifluridine and Tipiracil Hydrochloride
Given PO
Other Names:
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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:
Previously treated with >= 2 prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease
Able and willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
CROSSOVER INCLUSION CRITERIA: Previously treated with >= 2 prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease
CROSSOVER INCLUSION CRITERIA: Able and willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
Exclusion Criteria:
Prior treatment with drug targeting BRAF, MEK, ERK, or CDK family
Women of child-bearing potential
Sexually active males
Any symptomatic brain metastasis
Prior treatment =< 21 days prior to registration/randomization with any other chemotherapy, small molecule inhibitor (e.g. regorafenib), monoclonal antibody, immunotherapy, or radiotherapy
Impaired cardiovascular function or clinically significant cardiac diseases, including any of the following:
History of thromboembolic or cerebrovascular events =< 12 weeks prior registration/randomization. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or submassive) deep vein thrombosis or pulmonary emboli
Previous or concurrent malignancy =< 3 years prior to registration/randomization with the following exceptions:
Other solid tumors treated curatively without evidence of recurrence for >= 3 years prior to registration/randomization
CROSSOVER EXCLUSION CRITERIA: Prior treatment with drug targeting BRAF, MEK, ERK, or CDK family
CROSSOVER EXCLUSION CRITERIA: Women of child-bearing potential
CROSSOVER EXCLUSION CRITERIA: Sexually active males
CROSSOVER EXCLUSION CRITERIA: Any symptomatic brain metastasis
CROSSOVER EXCLUSION CRITERIA: Impaired cardiovascular function or clinically significant cardiac diseases, including any of the following:
United States, Arizona | |
Mayo Clinic in Arizona | Recruiting |
Scottsdale, Arizona, United States, 85259 | |
Contact: Clinical Trials Referrals Office 855-776-0015 | |
Principal Investigator: Tanios S. Bekaii-Saab | |
United States, Georgia | |
Emory University Hospital/Winship Cancer Institute | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: KJ Lee 404-778-3173 kyungjong.lee@emory.edu | |
Principal Investigator: Mehmet Akce | |
United States, Kansas | |
Cancer Center of Kansas - Wichita | Recruiting |
Wichita, Kansas, United States, 67214 | |
Contact: Shaker R. Dakhil shaker.dakhil@cancercenterofkansas.com | |
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 michele_vincitore@dfci.harvard.edu | |
Principal Investigator: Kimmie Ng | |
United States, North Carolina | |
UNC Lineberger Comprehensive Cancer Center | Recruiting |
Chapel Hill, North Carolina, United States, 27599 | |
Contact: Catherine A. Griffin 919-962-2621 catherine_griffin@med.unc.edu | |
Principal Investigator: Michael S. Lee | |
United States, Tennessee | |
Vanderbilt University/Ingram Cancer Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Contact: Thomas C. Leonard-Martin 800-293-5066 Thomas.Leonard-Martin@vumc.org | |
Principal Investigator: Kristen K. Ciombor | |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Scott Kopetz 507-266-0800 skopetz@mdanderson.org | |
Principal Investigator: Scott Kopetz |
Principal Investigator: | Scott Kopetz | Academic and Community Cancer Research United |
Tracking Information | |||||||
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First Submitted Date ICMJE | June 7, 2019 | ||||||
First Posted Date ICMJE | June 11, 2019 | ||||||
Last Update Posted Date | January 22, 2021 | ||||||
Actual Study Start Date ICMJE | October 29, 2019 | ||||||
Estimated Primary Completion Date | December 28, 2022 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Binimetinib and Palbociclib or TAS-102 in Treating Patients With KRAS and NRAS Mutant Metastatic or Unresectable Colorectal Cancer | ||||||
Official Title ICMJE | Combination of MEK Inhibitor Binimetinib and CDK4/6 Inhibitor Palbociclib in KRAS and NRAS Mutant Metastatic Colorectal Cancers | ||||||
Brief Summary | This phase II trial studies how well binimetinib and palbociclib work compared to TAS-102 in treating patients with KRAS and NRAS mutation positive colorectal cancer that has spread to other places in the body or cannot be removed by surgery. Binimetinib and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as TAS-102, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving binimetinib and palbociclib may work better compared to TAS-102 alone in treating patients with colorectal cancer. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
112 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | December 28, 2025 | ||||||
Estimated Primary Completion Date | December 28, 2022 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03981614 | ||||||
Other Study ID Numbers ICMJE | ACCRU-GI-1618 NCI-2019-03480 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ACCRU-GI-1618 ( Other Identifier: Academic and Community Cancer Research United ) P30CA015083 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Academic and Community Cancer Research United | ||||||
Study Sponsor ICMJE | Academic and Community Cancer Research United | ||||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||||
Investigators ICMJE |
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PRS Account | Academic and Community Cancer Research United | ||||||
Verification Date | January 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |