Binimetinib and Palbociclib Before Surgery for the Treatment of Operable KRAS-Positive Lung, Colorectal, or Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This early phase I trial studies the direct effects on cancer cells of the drugs binimetinib and palbociclib, in patients with KRAS-positive lung, colorectal, or pancreatic cancer that can be removed by surgery (operable). Binimetinib and palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving binimetinib and palbociclib may halt the growth of cancer cells and improve access of the immune system cells, a patient's own cells that fight infection and cancer, into the tumor.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVE: I. To determine the on-target efficacy of binimetinib and palbociclib in patients with operable RAS-mutant lung adenocarcinoma, colorectal, or pancreatic cancer. SECONDARY OBJECTIVES: I. Correlative analysis of gene expression analysis. II. Define immune subsets within the pre and post-treatment tumor tissue. OUTLINE: Patients receive palbociclib orally (PO) once daily (QD) and binimetinib PO twice daily (BID) for 14 days in the absence of disease progression or unacceptable toxicity. Within 1 week after last dose of study medication, patients undergo surgery. After completion of study treatment, patients are followed up at 30 days.

Intervention public domain (ClinicalTrials.gov)

Drug: Binimetinib. Given PO

Intervention public domain (ClinicalTrials.gov)

Drug: Palbociclib. Given PO

Intervention public domain (ClinicalTrials.gov)

Procedure: Therapeutic Conventional Surgery. Undergo surgery

Arm public domain (ClinicalTrials.gov)

Treatment (palbociclib, binimetinib) (experimental): Patients receive palbociclib PO QD and binimetinib PO BID for 14 days in the absence of disease progression or unacceptable toxicity. Within 1 week after last dose of study medication, patients undergo surgery.

Primary outcome public domain (ClinicalTrials.gov)

Change in Ki67 labeling index of > 70%. Pathologic response by change in Ki-67% from pre and surgical biopsies Time frame: Up to 30 days post treatment.

Primary outcome public domain (ClinicalTrials.gov)

Incidence of adverse events. Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies. Time frame: Up to 30 days post-treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Gene expression analysis. Time frame: Up to 30 days post-treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Immune subsets within the pre and posttreatment tumor tissue. Time frame: Up to 30 days post-treatment.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Age \>= 18 years of age * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Patients with verified and operable KRAS-positive mutant lung adenocarcinoma, colorectal, or pancreatic cancer * Have available diagnostic, pre-treatment archival tumor tissue * Medically fit for surgical resection * Absolute neutrophil count (ANC) \>= 1500/ uL * Hemoglobin (Hgb) \>= 9 g/dL * Platelet count \>= 100,000/uL * Total bilirubin =\< 1.5 x ULN (upper limit of normal) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2 x ULN * Creatinine clearance \> 60 mL/min (Cockcroft-Gault Equation) * Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present * Ability to swallow and retain oral medication * Female participants of childbearing potential must agree to use methods of contraception that are highly effective or acceptable, and to not donate ova from screening until 30 days after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Male participants must agree to use methods of contraception that are highly effective or acceptable, and to not donate sperm from screening until 90 days after the last dose of study drug * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Prior therapy with a CDK4/6 (e.g. palbociclib, ribociclib) or MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib) * Participants who have had any other systemic anticancer therapy within 2 weeks prior to entering the study * Is currently participating in a study and receiving an investigational agent; has received an investigational agent within 14 days prior to start of study treatment * Participants who have undergone major surgery =\< 6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure * Patient has not recovered to =\< grade 1 from toxic effects of prior therapy before starting study treatment. Note: Stable chronic conditions (=\< grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll * Uncontrolled or …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 0 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Issues recruiting