NCT03456804

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Mar 2018

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 9, 2018

Completed
26 days until next milestone

First Posted

Study publicly available on registry

March 7, 2018

Completed
1 day until next milestone

Study Start

First participant enrolled

March 8, 2018

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 15, 2023

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 9, 2023

Completed
2 months until next milestone

Results Posted

Study results publicly available

July 14, 2023

Completed
Last Updated

July 14, 2023

Status Verified

June 1, 2023

Enrollment Period

5 years

First QC Date

February 9, 2018

Results QC Date

March 29, 2023

Last Update Submit

June 24, 2023

Conditions

Castration Levels of TestosteroneCastration-Resistant Prostate CarcinomaMetastatic Prostate CarcinomaPSA ProgressionStage IV Prostate Adenocarcinoma AJCC v7

Outcome Measures

Primary Outcomes (1)

  • PSA Decline of >= 50% (PSA50) From Baseline

    PSA decline of \>= 50% (PSA50) from baseline using Prostate Cancer Working Group 3 (PCWG3) definition with point estimate and (1-sided Wilson type 90% lower) confidence interval (CI) estimates.

    Up to 1 year

Secondary Outcomes (3)

  • Duration of PSA Response (RD)

    From start of PSA50 until PSA progression, assessed up to 1 year

  • PSA Progression Free Survival (PFS)

    Date that a 25% or greater increase and an absolute increase of 2.0 ng/mL or more from the nadir is documented and confirmed by a second value obtained 3 or more weeks later, assessed up to 1 year

  • Time to PSA Response

    From treatment start until the first documented occurrence of PSA50, assessed up to 1 year

Other Outcomes (6)

  • Androgen Receptor (AR) Signaling

    Up to 1 year

  • Circulating and Disseminated Tumor Cells as Pharmacodynamic Biomarkers

    Up to 1 year

  • ETS/Kinase Gene Fusions

    Up to 1 year

  • +3 more other outcomes

Study Arms (1)

Treatment ESK981

EXPERIMENTAL

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.

Drug: ESK981

Interventions

ESK981DRUG

Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Treatment ESK981

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (1)

  • 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.

    PMID: 39227508DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Elisabeth Heath, M.D.
Organization
Karmanos Cancer Institute
heathe@karmanos.org
313-576-8717

Study Officials

  • Elisabeth I. Heath

    Barbara Ann Karmanos Cancer Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 9, 2018

First Posted

March 7, 2018

Study Start

March 8, 2018

Primary Completion

March 15, 2023

Study Completion

May 9, 2023

Last Updated

July 14, 2023

Results First Posted

July 14, 2023

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations

US(2)