Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer

Castration-resistant Prostate Cancer Clinical Trial

Official title:

Phase II Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05534646
• Other study ID #: IIT2021-06-Posadas-APA105
• Status: Recruiting
• Phase: Phase 2
• Start date: December 27, 2023
• Est. completion date: January 2027

Study information

• Verified date: February 2024
• Source: Cedars-Sinai Medical Center
• Contact: Clinical Trial Recruitment Navigator
• Phone: 3104232133
• Email: cancer.trial.info[@]cshs.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multi-site study of apalutamide with carotuximab in patients who have progressed on androgen receptor signaling inhibitor (ARSI) therapy. This study will begin with a safety assessment in the first 10 subjects (part 1: Safety Lead-in). If the combination is deemed safe, the trial will proceed to the Phase II stage. The purpose of this study is to compare progression free survival (PFS) between patients receiving apalutamide and apalutamide + carotuximab using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3. The secondary objectives are to describe adverse events related to the intervention, overall response rate (ORR), proportion of patients resistant to apalutamide that benefit from the addition of carotuximab, and to determine the ORR, radiographic PFS, and biochemical PFS in the overall population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: January 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• History of castration-resistant prostate cancer with rising PSA (prostate-specific antigen) on a contemporary ARSI (Androgen receptor (AR) signaling inhibitor: abiraterone, enzalutamide, darolutamide). Bicalutamide, nilutamide, and flutamide will not be considered as contemporary ARSIs
• Patient must have had 1 and can have up to 2 prior AR targeted therapy with the exception of apalutamide.
• Patients must decline or be ineligible for taxane therapy in the opinion of the treating physician.
• All patients must agree to use an adequate method of contraception, in the opinion of the treating investigator, while on protocol treatment and for 3 months after the last dose of protocol treatment (apalutamide and/or carotuximab)

Exclusion Criteria:

• Non-PSA producing prostate cancers such as small cell prostate cancers or those prostate cancers which exhibit radiographic progression without PSA rise
• Prior use of apalutamide
• Other prior malignancy requiring active anticancer therapy
• Prior exposure to carotuximab or any CD105 targeted antibody
• Active bleeding or pathologic medical conditions that carries a high bleeding risk
• A known diagnosis of Osler-Weber-Rendu syndrome

Related Conditions & MeSH terms

• Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Apalutamide
Standard of care Apalutamide 240 mg administered orally and daily on Days 1-28 of every 28 day cycle
• Carotuximab
Carotuximab administered intravenously at the following doses: Cycle 1 Day 1: 3 mg/kg Cycle 1 Day 4: 7 mg/kg Cycle 1 Day 8: 10 mg/kg Cycle 1 Day 15: 10 mg/kg Cycle 1 Day 22: 10 mg/kg Cycle 2 Day 1: 15 mg/kg Cycle 2 Day 15: 15 mg/kg Cycle 3+ Day 1: 15 mg/kg After completion of cycle 2, dosing of carotuximab will continue at a q4 week schedule using the 15 mg/kg dose.

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Edwin Posadas, MD	Enviro Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiographic progression free survival (rPFS) between patients receiving apalutamide and apalutamide + carotuximab	From the start of study treatment until documented progression, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3, or death due to any cause.	From the start of study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.
Secondary	Incidence of Adverse events (grade 3 or higher) related to carotuximab and apalutamide	Grade 3 or above treatment related adverse events as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	From start of study treatment through 4 weeks on treatment
Secondary	Overall radiographic response rate (ORR) of the combination of apalutamide + carotuximab	Participants of the combination of apalutamide + carotuximab, with confirmed complete response (CR) or partial response (PR) per RECIST v.1.1 and Prostate Cancer Working Group 3	From the start of combination study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.
Secondary	Proportion of patients resistant to apalutamide benefit from the addition of carotuximab	Participants of the monotherapy group that crossover to combination therapy at progression, with confirmed complete response (CR) or partial response (PR) per RECIST v.1.1 and Prostate Cancer Working Group 3	From the start of combination therapy study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.
Secondary	Overall radiographic response rate (ORR) in the overall population	Determined by confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3	From the start of study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.
Secondary	To determine the radiographic progression free survival (rPFS) in the overall population	From the start of study treatment until documented progression, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3, or death due to any cause.	From the start of study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.
Secondary	To determine the biochemical PFS (by PCWG3) in the overall population	From the start of study treatment until documented progression, per Prostate Cancer Working Group 3, or death due to any cause.	From the start of study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.