ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer

NCT ID: NCT03456804

Last Updated: 2023-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-08
• Study Completion Date: 2023-05-09

Brief Summary

This phase II trials studies the side effects and how well ESK981 works in treating patients with castration-resistant prostate cancer that has spread to other places in the body. ESK981 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the PSA >= 50% response rate (PSA50) from baseline using the Prostate Cancer Working Group 3 (PCWG3) criteria to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981) as a single agent in men with castration-resistant prostate cancer (CRPC) who have progressed on enzalutamide (an oral androgen-receptor inhibitor) and/or abiraterone acetate (an androgen synthesis inhibitor).

II. To assess the safety and tolerability of ESK981 as a single agent.

SECONDARY OBJECTIVES:

I. To determine the time to PSA response to ESK981 in metastatic CRPC patients. II. To determine the duration of PSA response to ESK981 in metastatic CRPC patients.

III. To determine PSA progression rates and PSA progression free survival (PFS), as defined by the PCWG3 criteria.

TERTIARY OBJECTIVES:

I. To assess exploratory biomarkers from blood and tumor biopsies.

OUTLINE:

Patients receive pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 orally (PO) once daily (QD) for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

After completion of study treatment, patients are followed up periodically.

Conditions

Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma AJCC v7

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment ESK981

Patients receive pan-VEGFR/TIE2 (Vascular Endothelial Growth Factor Receptor/angopoeitin receptor2) tyrosine kinase inhibitor CEP-11981 PO QD for 5 days (Monday-Friday). Treatment repeats for up to 8 weeks in the absence of disease progression or unacceptable toxicity. If treatment is successful after 8 weeks, patients may receive up to 6 months of pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

Group Type: EXPERIMENTAL

ESK981

Intervention Type: DRUG

Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Interventions

ESK981

Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study
• Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
• Eastern Cooperative Group (ECOG) performance status =< 1
• Patient must have evidence of castrate resistant prostate cancer as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL)
• Documented histologically confirmed adenocarcinoma of the prostate
• Metastatic prostate cancer (M1) as documented by appropriate medical imaging (i.e. computed tomography [CT]-scan, positron emission tomography [PET] scan or bone scan)
• Treatment failure of either abiraterone and/or enzalutamide as evidenced by a confirmed rising PSA (per PCWG3 criteria) and a castrate serum testosterone level (i.e. =< 50 mg/dL) while receiving treatment with either abiraterone and/or enzalutamide
• Willingness to use contraception by a method that is deemed effective by the Investigator throughout the treatment period and for at least 30 days following the last dose of therapy
• Willingness and ability to comply with study procedures and follow-up examination
• Able to swallow and retain oral medication

Exclusion Criteria

• Current systemic therapy (other than a gonadotrophin releasing hormone [GnRH] agonist/antagonist) for CRPC including:

• CYP-17 inhibitors (e.g. ketoconazole, abiraterone)
• Antiandrogens (e.g. bicalutamide, nilutamide)
• Second generation antiandrogens (e.g. enzalutamide, ARN-509, Galeterone)
• Immunotherapy (e.g. sipuleucel-T, ipilimumab)
• Chemotherapy (e.g. docetaxel, cabazitaxel)
• Greater than 2 lines of prior systemic therapy for CRPC
• Prior chemotherapy (e.g. docetaxel, cabazitaxel) for CRPC; prior docetaxel administered in the castrate-sensitive space is allowed
• Prior radiopharmaceutical therapy (e.g. radium-223, strontium-89, samarium-153, etc.) within the past year
• Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements
• Absolute neutrophil count (ANC) less than 1500/mm^3
• Platelet count less than 100000/mm^3
• Hemoglobin less than 9 g/dL
• Bilirubin greater than 1.5 times the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.0 times the ULN in the absence of known hepatic metastases, or ALT or AST greater than 3.0 times the ULN in the presence of known hepatic metastases
• The patient has a serum creatinine value greater than 1.5 mg/dL
• The patient has active brain metastases
• The patient is currently on warfarin or heparin therapy
• The patient has any pre-existing coagulopathy, recent hemoptysis, gross hematuria, or gastrointestinal bleeding, and a history of a clinically significant cardiovascular or cerebrovascular event within 12 months prior to study entry
• The patient has uncontrolled hypertension defined as a blood pressure measurement greater than 150 mm Hg systolic or 90 mm Hg diastolic with medication
• The patient has received any investigational drug within the past 4 weeks
• The patient has previously been enrolled in the study or received ESK981
• The patient has known hypersensitivity to gelatin or lactose monohydrate
• The patient has taken a medication known to be a potent inducer of CYP1A2, CYP2C8, or CYP3A4 within 4 weeks prior to the first dose of study drug
• The patient has taken a medication known to be a potent inhibitor of CYP1A2, CYP2C8, or CYP3A4 within 2 weeks prior to the first dose of study drug

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Elisabeth Heath

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elisabeth I. Heath

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

References

Heath EI, Chen W, Heilbrun L, Choi JE, Dobson K, Smith M, Maj T, Vaishampayan U, Kryczek I, Zou W, Chinnaiyan AM, Qiao Y. Phase II trial of multi-kinase inhibitor ESK981 in patients with metastatic castration-resistant prostate cancer. Invest New Drugs. 2024 Oct;42(5):566-574. doi: 10.1007/s10637-024-01463-x. Epub 2024 Sep 3.

Reference Type: DERIVED

PMID: 39227508 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2017-02330

Identifier Type: REGISTRY

Identifier Source: secondary_id

2017-065

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017-065

Identifier Type: -

Identifier Source: org_study_id