Binimetinib and Hydroxychloroquine in Treating Patients With KRAS Mutant Metastatic Pancreatic Cancer

NCT04132505 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2019-0191NCI-2019-04991
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose of hydroxychloroquine when given together with binimetinib in treating patients with KRAS gene mutated pancreatic cancer that has spread to other places in the body (metastatic). Binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hydroxychloroquine may prevent autophagy, a normal process in which a cell destroys proteins and other substances which may lead to cell death. Autophagy may prevent normal cells from developing into tumor cells, but it may also protect tumor cells by destroying anticancer drugs or substances taken up by them. Giving hydroxychloroquine together with binimetinib may work better in treating patients with pancreatic cancer compared to binimetinib alone.

Conditions

Metastatic Pancreatic Adenocarcinoma; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Will employ the Bayesian optimal interval (BOIN) design to find the MTD.

  Up to 30 days

Secondary Outcomes (4)

• Response rate

  Up to 1 year

• Incidence of adverse events

  Up to 1 year

• Progression free survival

  Up to 1 year

• Overall survival

  Up to 1 year

Other Outcomes (3)

• Somatic gene mutation profile

  Up to 1 year

• Markers of autophagy

  Up to 1 year

• Effect of this binimetinib/hydroxychloroquine treatment on changes in muscle and fat mass

  Up to 1 year

Study Arms (1)

Treatment (binimetinib, hydroxychloroquine)

EXPERIMENTAL

Patients receive binimetinib PO BID and hydroxychloroquine PO BID on days 1-14. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Hydroxychloroquine

Interventions

Binimetinib DRUG

Given PO

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

Treatment (binimetinib, hydroxychloroquine)

Hydroxychloroquine DRUG

Given PO

Treatment (binimetinib, hydroxychloroquine)

Eligibility Criteria

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

You may qualify if:

• Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report with radiologically identified metastases that meet Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Be willing and able to provide written informed consent for the trial.
• Have at least one measurable lesion by RECIST criteria.
• Have had prior treatment with at least one line of therapy for metastatic disease.
• Have had tumor mutation profiling from any Clinical Laboratory Improvement Act (CLIA) certified laboratory demonstrating a KRAS mutation. Liquid biopsy demonstrating KRAS mutation will be considered acceptable.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale.
• Absolute neutrophil count (ANC) \>= 1500/uL (specimens must be collected within 10 days prior to the start of trial treatment).
• Platelets \>= 100,000/uL (specimens must be collected within 10 days prior to the start of trial treatment).
• Hemoglobin \>= 9.0 g/dL (specimens must be collected within 10 days prior to the start of trial treatment).
• Creatinine OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) =\< 1.5 x upper limit of normal (ULN) OR \>= 50 mL/min for subjects with creatinine level \> 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• Total bilirubin =\< 1.5 x ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• Indirect bilirubin =\< ULN (specimens must be collected within 10 days prior to the start of trial treatment).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment).
• Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver metastases) (specimens must be collected within 10 days prior to the start of trial treatment).
• Serum albumin \> 3.3 mg/dl (specimens must be collected within 10 days prior to the start of trial treatment).

You may not qualify if:

• Has pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma, ampulla of Vater, periampullary, duodenal, or common bile duct malignancies. Poorly differentiated carcinoma may be included at the discretion of the investigator if histologic features suggest the possibility of adenocarcinoma.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational treatment within 2 weeks prior to the anticipated first dose of study treatment.
• Received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic drugs (e.g. erlotinib) within 14 days of the anticipated start of study treatment.
• Have undergone major surgery (e.g. inpatient procedures) =\< 6 weeks prior to the start of study treatment or who have not recovered from side effects of earlier such procedures.
• Have undergone radiation within 7 days prior to the start of treatment.
• Patient has not recovered to =\< grade 1 from toxic effects of prior therapy before starting study treatment. Note that alopecia, neuropathy, myalgias, and endocrinopathy are exceptions to this criteria.
• Impaired cardiovascular function or clinically significant cardiovascular disease 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);
• Triplicate average baseline corrected QT (QTc) interval \>= 480 ms.
• Impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (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.
• Had a solid organ or hematologic transplant.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

binimetinib; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shubham Pant

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 22, 2019
• First Posted: October 18, 2019
• Study Start: October 22, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 3, 2025

Record last verified: 2025-10

Locations

US (1)