phase 2 basket trial of ulixertinib (BVD-523) in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring MAPK pathway mutations (BVD-523-HCQ)  

ClinicalTrials.gov Identifier

NCT05221320

Institution Name

University of Arizona Cancer Center

Full Institution Address

Tucson Arizona 85719 United States

Institution Phone

(520) 694-9057

Additional Institutions

Please see Clinicaltrials.gov for all sites contact information: University of California San Francisco, University of Kansas Cancer Center, Rogel Cancer Center, University of Michigan Health, Washington University School of Medicine, Mount Sinai, Cleveland Clinic, Massey Cancer Center, and Virginia Commonwealth University

Principal Investigator

Rachna Schroff, MD

Principal Investigator Phone

(520) 694-2873

Principal Investigator Email

shroff@arizona.edu

Additional Principal Investigators

Please see all other sites contact information on Clinicaltrials.gov.

Study Coordinator

Brianna Loughran

Study Coordinator Phone

(520) 694-9057

Study Coordinator Email

bloughran@arizona.edu

Study Overview

This is an open-label, multicenter, phase II basket study of ulixertinib in combination with hydroxychloroquine in patients with advanced gastrointestinal malignancies harboring MAPK pathway mutations. The trial will have five baskets based on disease primary: cholangiocarcinoma, pancreatic, colorectal, esophageal, and gastric adenocarcinomas.

Enrollment Information

Ongoing

Study Start Date

20230820

Study End Date

20240619

Study Purpose

Primary study endpoints will include safety/toxicity as well as ORR by RECIST 1.1. The secondary endpoint for efficacy is progression-free survival. Exploratory endpoints include pharmacokinetics of both ulixertinib and hydroxychloroquine, as well as predictive biomarkers from blood and tumor tissue-based samples.

Inclusion Criteria

Male or female patient aged ≥ 18 years. Histologically confirmed esophageal adenocarcinoma, esophageal squamous cell carcinoma, GEJ adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma, extrahepatic cholangiocarcinoma, or colorectal adenocarcinoma harboring a MAPK-mutated GI malignancy: KRAS, NRAS, HRAS, BRAF non-V600, MEK 1/2 (MAP2K1/2), or ERK 1/2 (MAPK3/1). Progression on or during standard lines of therapy Measurable disease by RECIST 1.1 criteria by computed tomography (CT) or magnetic resonance imaging (MRI). Willing to provide a biopsy at the time points indicated on the Schedule of Activities. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 Male and female patients of childbearing potential agree to use highly effective contraception throughout the study and at least 90 days after the last study treatment administration.

Exclusion Criteria

Received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. Received radiotherapy ≤ 14 days prior to the first dose of study treatment Undergone major surgery ≤ 3 weeks prior to starting study drug or who have not fully recovered from major surgery. History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity).

Required Tests Prior to Study

Screening activities may only begin after a paitent has signed consent. Screening activities include gaining both cancer history as well as medical history and insuring patient meets eligibility criteria. A physical exam will be completed as well as blood chemistry, urinalysis, and an opthalmologic exam. Disease assessments will also be completed.

Potential Side Effects

Ulixertinib (ERK1/2 inhibitor) is an investigational drug but has been dosed in over 500 patients to date. Commonly reported treatment-related adverse events are consistent with other drugs that inhibit the MAPK pathway: fatigue, diarrhea, nausea, dermatitis aceneiform, and vomiting. However, phototoxicity, hematologic, hepatic, ophthalmologic, and cardiac effects have been noted in a small proportion of patients. Hydroxycholoroquine is an old drug that was originally approved for the treatment and prevention of malaria. While the exact mechanism of action is still not well understood, it has been shown to supress the process of autophagy. Hydroxychloroquine has a known risk for QT prolongation.

Financial Assistance Available

No

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