A Phase II Multicenter Trial of ESK981 in Patients With Select Solid Tumors

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: University of Michigan Rogel Cancer Center (other)

Phase: 2

Start date: April 19, 2024

Planned enrollment: 66

Trial ID: NCT05988918
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More trial details at ClinicalTrials.gov More info

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Investigational Drug AI Analysis

chevron Show for: ESK981 (CEP-11981, BOL-303213X)

TrialFetch AI Analysis

Goal: Assess whether ESK981 controls disease in three advanced cancer subtypes, primarily by measuring the proportion of patients alive and progression-free at 4 months in each cohort.

Patients: Adults with ECOG performance status 0–2 and evaluable advanced disease after progression on, or intolerance of, standard systemic therapy. Cohorts include pancreatic adenocarcinoma or adenosquamous carcinoma; pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 >20%; and metastatic prostate cancer with neuroendocrine features or clinical evidence of neuroendocrine differentiation. Adequate organ function is required; key exclusions include uncontrolled hypertension, significant recent cardiovascular or thromboembolic disease, and active infection.

Design: Multicenter, nonrandomized phase II trial with three disease-specific, single-arm cohorts. Each cohort has a separate interim analysis after 10 patients enroll.

Treatments: All participants receive oral ESK981, four capsules once daily for five consecutive days followed by two days off, repeated in 28-day cycles. ESK981 is an investigational kinase inhibitor targeting angiogenesis-related VEGFR-1, VEGFR-2, and Tie-2; preclinical work also identifies PIKfyve inhibition, which disrupts autophagy and alters immune signaling. In a phase I solid-tumor study, no objective responses occurred among 37 evaluable patients, although 51% had stable disease at six weeks or later. Small phase II studies in metastatic castration-resistant prostate cancer showed limited activity, and clinical benefit in the populations enrolled here remains unproven.

Outcomes: The primary endpoint is the proportion alive and progression-free at four months in each cohort. Secondary endpoints include confirmed objective response rate, duration of response, median progression-free survival, overall survival, and adverse events graded by CTCAE v5.0. Response is assessed using RECIST v1.1 for the pancreatic and gastrointestinal cohorts and RECIST v1.1 plus PCWG3 for the prostate cohort.

Burden on patient: Estimated moderate burden. Treatment is taken at home, but patients must follow a five-days-on, two-days-off schedule and maintain a pill diary. Screening requires laboratory testing and contrast CT and/or MRI, with subsequent imaging and safety assessments to evaluate response and toxicity. Archived tissue is requested if available; no mandatory new biopsy or intensive pharmacokinetic sampling is specified. Visit and scan frequency is not stated, so travel burden cannot be quantified.

Last updated: Sep 2026

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Sites (3)

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Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

No email / No phone

Status: Recruiting

Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

No email / 734-936-4991

Status: Recruiting

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

[email protected] / 800-622-8922

Status: Recruiting

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