- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03456804
ESK981 in Treating Patients With Metastatic Castrate-Resistant Prostate Cancer
An Open-Label, Parallel, Phase II Study of Single-Agent Oral ESK981 in Men With Castrate-Resistant Prostate Cancer (CRPC)
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Karmanos Cancer Institute
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Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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Treatment with ESK981 for patients with metastatic castrate resistant prostate cancer
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PSA Decline of >= 50% (PSA50) From Baseline
Time Frame: Up to 1 year
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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.
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Up to 1 year
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of PSA Response (RD)
Time Frame: From start of PSA50 until PSA progression, assessed up to 1 year
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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.
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From start of PSA50 until PSA progression, assessed up to 1 year
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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.
|
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
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Time to PSA Response
Time Frame: From treatment start until the first documented occurrence of PSA50, assessed up to 1 year
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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.
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From treatment start until the first documented occurrence of PSA50, assessed up to 1 year
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunohistochemistry (IHC) of Protein Markers
Time Frame: Up to 1 year
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Ki67, Receptor, CD31, NG2, desmin, PDGFR1/2, VEGFR1/2 immunohistochemistry graded 0, 1, 2, 3
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Up to 1 year
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Androgen Receptor (AR) Signaling
Time Frame: Up to 1 year
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Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
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Up to 1 year
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Circulating and Disseminated Tumor Cells as Pharmacodynamic Biomarkers
Time Frame: Up to 1 year
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Number of Circulating and disseminated tumor cells per 7.5ml as a pharmacodynamic biomarker.
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Up to 1 year
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ETS/Kinase Gene Fusions
Time Frame: Up to 1 year
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Will examine the association of somatic and germline mutations with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981.
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Up to 1 year
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Metastatic Kinome Activity Profiles as Predictive Biomarkers
Time Frame: Up to 1 year
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Description of immunohistochemistry of the kinases, graded 0,1,2,3
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Up to 1 year
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DNA Sequencing of Prostate Tumor
Time Frame: Up to 1 year
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copy number, Loss of heterozygosity, mutation, amplification, graded 0,1
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Up to 1 year
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Elisabeth I. Heath, Barbara Ann Karmanos Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-065 (Other Identifier: Wayne State University/Karmanos Cancer Institute)
- P30CA022453 (U.S. NIH Grant/Contract)
- NCI-2017-02330 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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