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

NCT04870034 | Withdrawn Early Phase 1 DMC FDA Drug

• 2 other identifiers: I 797920NCI-2021-02908
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Carcinoma; Lung Adenocarcinoma; Malignant Solid Neoplasm; Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (2)

• Change in Ki67 labeling index of > 70%

  Pathologic response by change in Ki-67% from pre and surgical biopsies

  Up to 30 days post treatment

• 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.

  Up to 30 days post-treatment

Secondary Outcomes (2)

• Gene expression analysis

  Up to 30 days post-treatment

• Immune subsets within the pre and posttreatment tumor tissue

  Up to 30 days post-treatment

Study Arms (1)

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.

Drug: Binimetinib; Drug: Palbociclib; Procedure: Therapeutic Conventional Surgery

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162, Mektovi

Treatment (palbociclib, binimetinib)

Palbociclib DRUG

Given PO

Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991

Treatment (palbociclib, binimetinib)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (palbociclib, binimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Note: Patients with previously treated brain metastases may participate provided they are stable (e.g., without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline), and have no evidence of new or enlarging brain metastases or central nervous system (CNS) edema, and does not require steroids at least 7 days before the first dose of study treatment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Impaired cardiovascular function or clinically significant cardiac diseases including, but not limited to, any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \< 6 months prior to screening
• Congestive heart failure requiring treatment (New York Heart Association grade \>= 2)
• Left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition scan (MUGA) or echocardiography (ECHO)
• Uncontrolled hypertension defined as persistent systolic blood pressure \>= 150 mmHg or diastolic blood pressure \>= 100 mmHg despite current therapy
• History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
• Baseline corrected QT (QTc) interval \>= 480 ms
• Impairment of gastrointestinal function or disease which may significantly alter the absorption of binimetinib or palbociclib (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=\< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Adenocarcinoma of Lung; Pancreatic Neoplasms

Interventions

binimetinib; palbociclib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Christos Fountzilas

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: May 3, 2021
• Study Start: January 15, 2024
• Primary Completion: September 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: December 22, 2023

Record last verified: 2023-12

Locations

US (1)