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Trial record 37 of 207 for:    Oral Cancer | Recruiting Studies | NIH

ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03456804
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : March 15, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Elisabeth Heath, Barbara Ann Karmanos Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma PSA Progression Stage IV Prostate Adenocarcinoma AJCC v7 Drug: ESK981 Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Parallel, Phase II Study of Single-Agent Oral ESK981 in Men With Castrate-Resistant Prostate Cancer (CRPC)
Actual Study Start Date : March 8, 2018
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : October 31, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: 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.
Drug: ESK981
Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer




Primary Outcome Measures :
  1. PSA decline of >= 50% (PSA50) from baseline Prostate Cancer Working Group 3 (PCWG3) [ Time Frame: Up to 1 year ]
    All analyses point and (1-sided Wilson type 90% lower) confidence interval (CI) estimates will be calculated.


Secondary Outcome Measures :
  1. Duration of PSA response (RD) [ Time Frame: From start of PSA50 until PSA progression, assessed up to 1 year ]
    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.

  2. PSA progression free survival (PFS) [ Time Frame: 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 ]
    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.

  3. Time to PSA response [ Time Frame: From treatment start until the first documented occurrence of PSA50, assessed up to 1 year ]
    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.


Other Outcome Measures:
  1. Androgen receptor (AR) signaling [ Time Frame: Up to 1 year ]
    Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

  2. Circulating and disseminated tumor cells as pharmacodynamic biomarkers [ Time Frame: Up to 1 year ]
    Number of cells per 7.5ml

  3. ETS/kinase gene fusions [ Time Frame: Up to 1 year ]
    Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.

  4. Metastatic kinome activity profiles as predictive biomarkers [ Time Frame: Up to 1 year ]
    Description of immunohistochemistry of the kinases, graded 0,1,2,3

  5. Immunohistochemistry (IHC) of Protein Markers [ Time Frame: Up to 1 year ]
    Ki67, Receptor, CD31, NG2, desmin, PDGFR1/2, VEGFR1/2 immunohistochemistry graded 0, 1, 2, 3

  6. DNA Sequencing of prostate tumor [ Time Frame: Up to 1 year ]
    copy number, Loss of heterozygosity, mutation, amplification, graded 0,1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456804


Locations
United States, Michigan
Wayne State University/Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Elisabeth I. Heath    313-576-8717    heathe@karmanos.org   
Principal Investigator: Elisabeth I. Heath, M.D.         
Sub-Investigator: Ulka N. Vaishampayan, M.D.         
Sub-Investigator: Joseph Fontana, M.D.         
United States, Washington
Seattle Cancer Care Alliance Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Michael Schweizer    206-288-6252    schweize@u.washington.edu   
Principal Investigator: Michael Schweizer         
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Elisabeth I. Heath Barbara Ann Karmanos Cancer Institute

Responsible Party: Elisabeth Heath, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT03456804     History of Changes
Other Study ID Numbers: 2017-065
NCI-2017-02330 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-065 ( Other Identifier: Wayne State University/Karmanos Cancer Institute )
P30CA022453 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Carcinoma
Adenocarcinoma
Genital Diseases, Male
Prostatic Diseases