ESK981 and Nivolumab for the Treatment of Metastatic Castration Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT04159896|
Recruitment Status : Recruiting
First Posted : November 12, 2019
Last Update Posted : October 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Metastatic Prostate Carcinoma Prostate Carcinoma Metastatic in the Bone Stage IVB Prostate Cancer AJCC v8||Drug: Pan-VEGFR/TIE2 Tyrosine Kinase Inhibitor CEP-11981 Biological: Nivolumab||Phase 2|
I. To determine the prostate specific antigen (PSA) >= 50% response rate (PSA50) from baseline using the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981) plus nivolumab in men with metastatic castration resistant prostate cancer (mCRPC) who have progressed on enzalutamide (an oral androgen-receptor inhibitor) and/or abiraterone acetate (an androgen synthesis inhibitor) and chemotherapy (docetaxel and/or cabazitaxel).
II. To assess the safety and tolerability of ESK981 plus nivolumab.
I. To determine the time to PSA response (TTPR) in patients with mCRPC. II. To determine the duration of PSA response (PRD) in patients with mCRPC. III. To determine PSA progression rates as defined by the PCWG3 criteria. IV. To determine PSA progression free survival (PPFS) as defined by the PCWG3 criteria.
I. To assess exploratory biomarkers from blood and tumor biopsies.
Patients receive ESK981 orally (PO) once daily (QD) for 5 consecutive days per week, followed by a 2-day break. Patients also receive nivolumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Multi-Center Trial of ESK981 in Combination With Nivolumab in Patients With Metastatic Castrate Resistant Prostate Cancer|
|Actual Study Start Date :||November 13, 2019|
|Estimated Primary Completion Date :||March 1, 2022|
|Estimated Study Completion Date :||March 1, 2022|
Experimental: Treatment (ESK981, nivolumab)
Patients receive ESK981 PO QD for 5 consecutive days per week, followed by a 2-day break. Patients also receive nivolumab IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Pan-VEGFR/TIE2 Tyrosine Kinase Inhibitor CEP-11981
- Prostate specific antigen (PSA) >= 50% response rate (PSA50) [ Time Frame: Up to 5 years ]Will assess PSA decline of >= 50% from baseline (PSA50), using the Prostate Cancer Working Group 3 (PCWG3) criteria. 1-sided Wilson type 90% lower confidence interval (CI) estimates will be calculated.
- Incidence of adverse events [ Time Frame: Up to 30 days after last dose ]Adverse events of all grades will be captured by the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 5 (NCI-CTCAE v5) and Good Clinical Practice (GCP) standards. Other statistics will include point and (2-sided) CI estimates of overall toxicity and of specific types of toxicity.
- Time to PSA response (TTPR) [ Time Frame: From treatment start until the first documented occurrence of PSA50, assessed up to 5 years ]Descriptive statistics of TTPR will be used to summarize the time to PSA response. These descriptives will include N, median, mean, standard deviation (SD), interquartile range (IQR), minimum, and maximum.
- Duration of PSA response (PRD) [ Time Frame: From start of PSA50 until PSA progression, assessed up to 5 years ]The censored distributions will be summarized with the Kaplan-Meier (K-M) survivorship estimate. A graph of the K-M curve 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.
- PSA progression free survival (PPFS) [ Time Frame: Up to 5 years ]PSA progression rates will be estimated from the PSA-only PFS distribution. PSA progression is defined as the 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. Where no decline from baseline is documented, PSA progression is defined as a 25% increase from the baseline value along with an increase in absolute value of 2.0 ng/mL or more after 8 weeks. The censored distributions will be summarized with the K-M survivorship estimate. A graph of the K-M curve 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.
- Somatic and germline mutations [ Time Frame: Up to 5 years ]Will assess the proportion of patients with TP53 mutations, AR amplifications, and ETS-fusions, mutations in the PTENPI3K-AKT pathway as well as germline and somatic events in the DNA repair pathway with exceptional response/resistance to pan-VEGFR/TIE2 tyrosine kinase inhibitor CEP-11981 (ESK981).
- ETS/kinase gene fusions [ Time Frame: Up to 5 years ]Will assess the proportion of patients with ETS/kinase gene fusions with exceptional response/resistance to ESK981.
- Androgen receptor (AR) signaling [ Time Frame: Up to 5 years ]Will assess the correlation of AR signaling as a predictor of exceptional response to ESK981.
- Metastatic kinome activity profiles as predictive biomarkers for response to ESK981 [ Time Frame: Up to 5 years ]Will assess the correlation of Metastatic kinome activity profiles as a predictor for exceptional response to ESK981
- Circulating and disseminated tumor cells as pharmacodynamic biomarkers of ESK981 response [ Time Frame: Up to 5 years ]Will assess the correlation of circulating and disseminated tumor cells as a predictor for exceptional response to ESK981 .
- Pathological assessment of phenotypic tumor and host responses to ESK981 treatment [ Time Frame: Up to 5 years ]Will assess the correlation of IHC % staining as a predictor for exceptional response to ESK981 .
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): NCT04159896
|Contact: Elisabeth Heath, M.D.||firstname.lastname@example.org|
|Contact: Karmanos Cancer Institute||800-527-6266|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Ajjai Alva, M.D 734-936-0091 email@example.com|
|Wayne State University/Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Elisabeth I. Heath 313-576-8717 firstname.lastname@example.org|
|Principal Investigator: Elisabeth I. Heath, M.D.|
|Sub-Investigator: Ulka N. Vaishampayan, M.D.|
|Sub-Investigator: Joseph Fontana, M.D.|
|Principal Investigator:||Elisabeth Heath, M.D.||Barbara Ann Karmanos Institute|