sEphB4-HSA in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT04033432|
Recruitment Status : Recruiting
First Posted : July 26, 2019
Last Update Posted : October 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Castration Levels of Testosterone Castration-Resistant Prostate Carcinoma Castration-Resistant Prostate Carcinoma Refractory to Second-Generation Androgen Receptor Axis-Targeted Agents Metastatic Prostate Adenocarcinoma Progressive Disease Prostate Carcinoma Metastatic in the Bone Prostate Carcinoma Metastatic in the Soft Tissue PSA Progression Stage IVB Prostate Cancer AJCC v8 Testosterone Less Than 50 ng/dL||Biological: Recombinant EphB4-HSA Fusion Protein||Phase 2|
I. To estimate the efficacy of recombinant EphB4-HSA fusion protein (sEphB4-HSA) in patients with metastatic castration resistant prostate cancer (mCRPC) as measured by confirmed prostate specific antigen (PSA) response rate.
I. The safety and tolerability of sEphB4-HSA in patients with mCRPC according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
II. To assess the time to PSA progression. III. To assess overall response rate in patients with measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (soft tissue) and Prostate Cancer Working Group 3 (PCWG3) (bone) criteria.
IV. To assess radiological progression free survival (rPFS) using RECIST 1.1 (soft tissue) and PCWG3 (bone) criteria.
I. To explore molecular changes associated with EphB4 and ephrinB2 expression in tumor specimens (primary and/or metastatic tissue).
II. To explore association of response with molecular biomarkers including aberrations in the PI3K pathway, MYC and TP53.
III. To assess immune cell infiltration of tumors in biopsies. IV. To assess circulating immune changes associated with treatment.
Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for cycles 1-6 and then every 21 days for subsequent cycles. Patients may continue to receive sEphB4-HSA treatment until no longer clinically benefiting (PCWG3), unacceptable toxicity, treatment delay >= 4 weeks, or prohibitive illness/change in patient?s condition, or patient decides to withdraw from study.
After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of sEphB4-HSA in Metastatic Castration-Resistant Prostate Cancer|
|Actual Study Start Date :||September 20, 2019|
|Estimated Primary Completion Date :||June 3, 2021|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Treatment (recombinant EphB4-HSA fusion protein)
Patients receive recombinant EphB4-HSA fusion protein IV over 60 minutes on day 1. Treatment repeats every 14 days for cycles 1-6 and then every 21 days for subsequent cycles. Patients may continue to receive sEphB4-HSA treatment until no longer clinically benefiting (PCWG3), unacceptable toxicity, treatment delay >= 4 weeks, or prohibitive illness/change in patient?s condition, or patient decides to withdraw from study.
Biological: Recombinant EphB4-HSA Fusion Protein
Other Name: sEphB4-HSA
- Prostate specific antigen (PSA) response rate [ Time Frame: Up to 1 year ]Will be evaluated per the Prostate Cancer Working Group 3 (PCWG3) criteria. PSA response rate is defined as the proportion of subjects who received at least 1 dose of the study drug achieving a post-treatment PSA partial response or complete response as defined by PSA response criteria.
- Incidence of adverse events [ Time Frame: Up to 1 year ]Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and reported by the toxicity, severity, and attribution will be recorded for each cycle. All reported adverse event (AE) types will be tabulated by maximum grade using frequencies and percentages. Data on type, timing, frequency and attribution of AEs will also be summarized.
- Time to PSA progression [ Time Frame: From the start of study treatment to PSA progression, assessed for up to 1 year ]The time to PSA progression will be assessed by calculating the interval from administration of the first dose of drug on cycle 1 day 1 to PSA progression. PSA progression is defined by the criteria. PSA will be assessed every odd cycle. Will use Kaplan Meier methods to estimate the distribution of time to PSA progression. Will estimate the median with two-sided 90% confidence interval (CI).
- Overall response rate [ Time Frame: Up to 1 year ]The overall response rate will be the proportion of patients with measurable disease who received at least 1 dose of the study drug and as their best response achieved a partial or complete response (responder). Will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and PCWG3 criteria. Will be reported with two-sided 90% exact binomial CI.
- Time to radiologic progression (rPFS) [ Time Frame: From the start of study treatment to the time of radiologic progression or death from any cause, assessed for up to 1 year ]The time to rPFS will be assessed by calculating the interval from administration of the first dose of drug on cycle 1 day 1 to the time to radiologic progression by RECIST 1.1 or PCWG3 bone criteria or death from any cause. Radiologic assessment will be every 8 weeks. Will use Kaplan Meier methods to estimate the distribution of rPFS. Will estimate the median with two-sided 90% confidence interval (CI).
- Changes in EphB4 and ephrinB2 expression [ Time Frame: Baseline up to 1 year ]EphB4 and ephrinB2 expression will be assessed by immunohistochemistry (IHC) staining of primary and/or metastatic site (recent archival specimen or new biopsy). EphB4 and other biomarker abnormalities will be assessed by next generation sequencing of metastatic tissue. Will explore if PSA response is associated with expression of EphB4 and ephrinB2 in archival metastatic and primary tumor CRPC specimens. Summaries will be descriptive and graphical.
- Circulating tumor-derived deoxyribonucleic acid (ctDNA) analysis of PI3K pathway, MYC or TP53 [ Time Frame: Up to 1 year ]ctDNA will be analyzed for abnormalities in PI3K pathway, MYC or TP53. Summaries will be descriptive and graphical.
- Immune infiltrate characterization in tumor specimen [ Time Frame: Up to 1 year ]The study will use IHC for CD3, CD4, CD8, and natural-killer cell markers to characterize the immune infiltrate in tumor specimen.
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): NCT04033432
|Contact: Study Coordinator||(312)firstname.lastname@example.org|
|United States, California|
|USC / Norris Comprehensive Cancer Center||Not yet recruiting|
|Los Angeles, California, United States, 90033|
|Contact: David I. Quinn email@example.com|
|Principal Investigator: David I. Quinn|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Maha H. Hussain, M.D. 312-908-5487 firstname.lastname@example.org|
|Principal Investigator: Maha H. Hussain, M.D.|
|University of Chicago Comprehensive Cancer Center||Not yet recruiting|
|Chicago, Illinois, United States, 60637|
|Contact: Walter M. Stadler email@example.com|
|Principal Investigator: Walter M. Stadler|
|Principal Investigator:||Maha H Hussain, M.D.||Northwestern University|