Trametinib and Hydroxychloroquine in Treating Patients With Pancreatic Cancer

NCT03825289 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HCI116898
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I trial studies the sides effects and best dose of hydroxychloroquine when given together with trametinib in treating patients with pancreatic cancer that has spread to nearby tissue, lymph nodes or other places in the body and cannot be removed by surgery. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as hydroxychloroquine, 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 trametinib together with hydroxychloroquine may work better in treating patients with pancreatic cancer.

Conditions

Metastatic Pancreatic Carcinoma; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer; Unresectable Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Rate of dose-limiting toxicities during the DLT assessment window.

  To determine the recommended phase II dose (RP2D) hydroxychloroquine in combination with trametinib.

  At 28 days

Secondary Outcomes (2)

• Incidence of adverse events (AEs) for the duration of study treatment

  30 days after last dose

• Response Rate

  5 years

Study Arms (1)

Treatment (trametinib, hydroxychloroquine)

EXPERIMENTAL

Patients receive trametinib PO QD on days 1-28 and hydroxychloroquine PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Hydroxychloroquine; Drug: Trametinib

Interventions

Hydroxychloroquine DRUG

Given PO

Treatment (trametinib, hydroxychloroquine)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

Treatment (trametinib, hydroxychloroquine)

Eligibility Criteria

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

You may qualify if:

• Subject with histologically confirmed metastatic or locally advanced, unresectable pancreatic carcinoma
• Subject is willing to provide a baseline biopsy.
• EXPANSION COHORT ONLY: Subject must have progressed during or after two standard of care lines of treatment or refused standard of care options.
• Subject must have computed tomography (CT) measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• Subject must be able and willing to undergo disease assessment while on study and afterwards, if removed for reason other than progression
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Total bilirubin level =\< 1.5 x the upper limit of normal (ULN) range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =\< 3 x ULN. Patients with liver metastases will be allowed to enroll with AST and ALT levels =\< 5 x ULN
• Estimated creatinine clearance \>= 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• Negative serum or urine pregnancy test at screening for women of childbearing potential
• Highly effective contraception for both male and female subjects throughout the study and for at least 4 months after last study treatment administration
• Recovery to baseline or =\< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless adverse event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy

You may not qualify if:

• Subject who have received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy within 2 weeks or within 5 half-lives of the investigational therapy prior to starting study treatment, whichever is shorter.
• Subject who have received radiotherapy within 2 weeks prior to the first dose of study treatment. Localized radiation therapy for the treatment of symptomatic bone metastasis is allowed during that timeframe
• Subjects who have undergone major surgery =\< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
• Patients with multiple primary malignancies may be enrolled if non-pancreatic ductal adenocarcinoma (PDAC) tumor(s) does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as determined by treating investigator and do not require active treatment
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• History of active major bleeding.
• Patients whom thromboembolic prophylaxis is medically contraindicated per the treating investigator's assessment.
• Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before first dose. The presence of an asymptomatic portal vein thrombosis will not preclude study participation.
• History of glucose-6-phosphate dehydrogenase (G6PD) deficiency
• History of seizures
• Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. Muscular activities, such as strenuous exercise, that can result in significant increases in plasma creatine kinase (CK) levels should be avoided while on study treatment

Sponsors & Collaborators

• University of Utah: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Hydroxychloroquine; trametinib

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

• Conan Kinsey, MD

  Huntsman Cancer Institute/ University of Utah

  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: January 30, 2019
• First Posted: January 31, 2019
• Study Start: January 18, 2019
• Primary Completion: January 15, 2025
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)