Multicenter Trial of ESK981 in Patients With Select Solid Tumors

NCT05988918 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: UMCC 2023.005HUM00233810
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

This protocol will enroll patients with pancreatic adenocarcinoma and adenosquamous carcinoma (Cohort 1), gastrointestinal/pancreatic neuroendocrine neoplasms with Ki-67 \> 20% (Cohort 2) and neuroendocrine prostate carcinoma (Cohort 3)). Each cohort will have its own interim analysis after enrollment of 10 patients. Subjects will be given a one-month (28 day) supply of study drug (ESK981). Subjects will be instructed to take 4 capsules, with or without food, once per day for 5 consecutive calendar days, then take a drug holiday for 2 consecutive days before repeating the 5 days on-2 days off cycle in sets of 4 weeks or 28 calendar days. Subjects will be asked to keep a pill diary noting the date they take their study drug.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Determining efficacy using proportion of patients alive and progression-free at 4 months within each cancer subtype

  4 months after initiating study drug

Secondary Outcomes (5)

• Overall Response Rate (ORR) within each cancer subtype

  up to 18 months from treatment discontinuation

• Duration of Response (DoR) within each cancer subtype

  up to 18 months from treatment discontinuation

• Overall Survival (OS) within each cancer subtype

  up to 18 months from treatment discontinuation

• Safety and tolerability in each cancer subtype

  up to 30 days from treatment discontinuation

• Median Progression- Free Survival (PFS) within each cancer subtype

  up to 18 months from treatment discontinuation

Study Arms (3)

Cohort 1

EXPERIMENTAL

Pancreatic adenocarcinoma

Drug: ESK981

Cohort 2

EXPERIMENTAL

Pancreatic or gastrointestinal neuroendocrine neoplasms with Ki-67 \> 20%

Drug: ESK981

Cohort 3

EXPERIMENTAL

Neuroendocrine prostate carcinoma with Ki-67 \> 20%

Drug: ESK981

Interventions

ESK981 DRUG

160 mg, PO, Once daily 5 days on and 2 days off

Also known as: CEP-11981

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

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

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (3)

Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Adenosquamous; Adenoma, Islet Cell; Somatostatinoma; Gastro-enteropancreatic neuroendocrine tumor

Interventions

11-(2-methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo(5,4-a)pyrrolo(3,4-c)carbazol-4-one

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenoma; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Carcinoma, Islet Cell

Study Officials

• Vaibhav Sahai

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: April 19, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)