Testing ESK981 in patients with certain types of solid tumors

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

This study is testing a new drug called ESK981 to see if it can help people with advanced solid tumors like pancreatic cancer and neuroendocrine tumors who haven't had success with standard chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Michigan Rogel Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 3 sites (Ann Arbor, Michigan and 2 other locations)
• Trial ID: NCT05988918 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy of ESK981 in patients with advanced solid tumors, specifically pancreatic adenocarcinoma, adenosquamous carcinoma, and gastrointestinal neuroendocrine tumors. The trial is divided into three cohorts, each focusing on different tumor types and requiring patients to have progressed or been intolerant to standard chemotherapy. Participants will take ESK981 in a specific dosing schedule of five days on and two days off, while maintaining a pill diary to track their medication intake. Interim analyses will be conducted after enrolling 10 patients in each cohort to assess the drug's effectiveness.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced pancreatic or gastrointestinal neuroendocrine tumors who have not responded to standard therapies.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have limited treatment alternatives.

How similar studies have performed: While this approach is being tested in this specific context, similar studies have shown promise in targeting advanced solid tumors with novel therapies.

Eligibility criteria

Eligibility Criteria:

* Patients with histological or cytological confirmation of advanced cancer per specific cohort.

  * Cohort 1: Pancreatic adenocarcinoma or adenosquamous carcinoma who have progressed or deemed intolerant of the standard of care chemotherapy regimens.
  * Cohort 2: Pancreatic or gastrointestinal neuroendocrine tumor or carcinoma with Ki-67 \> 20% who have progressed or deemed intolerant of at least first-line standard of care systemic therapy.
  * Cohort 3: The subject has histologically proven prostate cancer who have progressed or deemed intolerant of at least first-line standard of care systemic therapy with radiologic evidence of metastases and at least one of the following:

    * Small cell or neuroendocrine morphology on the basis of tissue sample.
    * Prostate adenocarcinoma with IHC staining for neuroendocrine markers (e.g., chromogranin and synaptophysin).
    * Presence of visceral metastases or high-volume disease (\> 4 sites of metastases) with a PSA ≤ 5.
    * Serum chromogranin A level ≥ 5x upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2x ULN.
    * Trans-differentiated carcinoma or poorly-differentiated carcinoma
* Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
* Must be ≥ 18 years of age.
* Evaluable disease determined using guidelines of Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)
* Ability to understand and willingness to sign IRB-approved informed consent.
* Willing to provide archived tissue, if available, from a previous diagnostic biopsy.
* Must be able to tolerate CT and/or MRI with contrast.
* At least 4 weeks from major surgery with resolution of any sequela to date of enrollment
* Laboratory values ≤2 weeks during screening must be:

  * Platelet count ≥ 75,000 cells/mm3
  * Absolute neutrophil count ≥ 1500 cells/mm3
  * Hemoglobin ≥ 9 g/dL
  * AST/ALT ≤ 3x upper limit of normal \[ULN\], or (≤ 5x ULN if liver metastasis present)
  * Bilirubin ≤ 1.5x ULN, or (≤ 2.5 x ULN for subjects with Gilbert's syndrome)
  * Albumin ≥ 3 g/dL
  * Serum creatinine clearance CrCl ≥ 50 mL/min per Cockcroft-Gault Formula
  * INR ≤ 1.5 (or \<2.0 if on anticoagulants)
* Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must agree to use acceptable highly effective contraceptive methods (abstinence, intrauterine device \[IUD\], oral contraceptive(s), intrauterine hormone releasing system (IUS), bilateral tubal occlusion or vasectomized partner) during and for 9 months after last study dose and must have a negative serum or urine pregnancy test during screening.
* Males with female partners (of childbearing potential) and female partners (of childbearing potential) with male partners must agree to use double barrier contraceptive measure (a combination of male condom with either cap, diaphragm or sponge with spermicide) in addition to oral contraception, or avoidance of intercourse during the study and for 6 months after last study dose is received.
* Female patients must not be pregnant, have a positive pregnancy test, breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 9 months after the last dose of study treatment.
* Male patients must be willing to abstain from donating sperm during treatment and for 6 months after completion of study treatment.
* No evidence of active infection and no serious infection within the past 30 days. Patient must have completed antibiotic course.
* No known cerebral metastasis, central nervous system (CNS), or epidural tumor (unless previously treated, asymptomatic and stable for at least 3 months).
* No active heart disease including but not limited to myocardial infarction that is \<3 months prior to registration, symptomatic congestive heart failure (NYHA class 3 or 4), symptomatic coronary artery disease, symptomatic angina pectoris.
* No history of acute cerebrovascular disease, arterial or venous thromboembolism, percutaneous angioplasty, or coronary artery bypass surgery within 6 months prior to registration
* No pre-existing coagulopathy, or serious bleeding within 3 months prior to registration.
* No prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cancer, localized prostate cancer (Gleason score \<8), or adequately treated cancer from which the patient has been disease-free for at least 3 years prior to registration.
* Must not have uncontrolled diarrhea at the time of enrollment.
* Patients must not use a chronic daily medication known to be a strong or moderate inhibitor of CYP1A2, CYP2C8 or CYP3A4 at registration (as per Appendix II).
* Patients must have recovered to baseline or ≤ grade 1 CTCAE v5.0 from toxicities related to any prior treatments, unless adverse event(s) is deemed clinically non-significant and/or stable on supportive therapy.
* Patients must not have uncontrolled hypertension defined as blood pressure \>150/90 despite optimal medical management.
* No known hypersensitivity to gelatin or lactose monohydrate.

Where this trial is running

Ann Arbor, Michigan and 2 other locations

• Rogel Cancer Center — Ann Arbor, Michigan, United States (Active_not_recruiting)
• Barbara Ann Karmanos Cancer Institute — Detroit, Michigan, United States (Withdrawn)
• University of Wisconsin Carbone Cancer Center — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Vaibhav Sahai — University of Michigan
• Study coordinator: Cancer AnswerLine

Conditions Pancreatic Adenocarcinoma; Adenosquamous Carcinoma; Pancreatic Neuroendocrine Tumor; Pancreatic Neuroendocrine Carcinoma; Gastrointestinal Neuroendocrine Tumor; Gastrointestinal Neuroendocrine Carcinoma; Neuroendocrine Prostate Carcinoma