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Castration Levels of TestosteronePhase 2NCT03456804

ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer

A Phase 2 study testing ESK981 in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
ESK981
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
2 sitesUnited States
Study dates
8 Mar 2018to 9 May 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: An Open-Label, Parallel, Phase II Study of Single-Agent Oral ESK981 in Men With Castrate-Resistant Prostate Cancer (CRPC)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
ESK981
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ESK981Drug

    Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer

Study groups in NCT03456804
Study groupRoleWhat they receive
Treatment ESK981ExperimentalPatients 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.
Receives: Drug: ESK981

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 1 year

Secondary outcomes (3)

  1. Duration of PSA Response (RD)

    Will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for RD will be generated along with the Hall-Wellner 90% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (6-month rate, 12-month rate, median, etc.) will be calculated from the K-M life table, each one with its respective 80% CI.

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

  2. PSA Progression Free Survival (PFS)

    Will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve for PFS will be generated along with the Hall-Wellner 90% confidence band, and a display of the number of patients at risk at several time points, below the X-axis. Summary statistics (6-month rate, 12-month rate, median, etc.) will be calculated from the K-M life table, each one with its respective 80% CI.

    Measured: 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

  3. Time to PSA Response

    Will be used to summarize the time to PSA response. These descriptives will include sample size (N), median, mean, standard deviation (SD), interquartile range (IQR), minimum, and maximum.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2018
  2. Study start8 Mar 2018
  3. Primary completion15 Mar 2023
  4. Study completion9 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03456804
Sponsor's protocol ID
2017-065
Other IDs
NCI-2017-02330, 2017-065, P30CA022453
Status last verified
Jun 2023
First submitted
9 Feb 2018
Last updated
14 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39227508

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ESK981 in people with Castration Levels of Testosterone and Castration-Resistant Prostate Carcinoma, run by Barbara Ann Karmanos Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA Decline of >= 50% (PSA50) From Baseline (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03456804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2023.

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