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

Phase 2
Recruiting
Conditions
Castration-resistant Prostate Cancer
Interventions
Registration Number
NCT05534646
Lead Sponsor
Edwin Posadas, MD
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
Male
Target Recruitment
100
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Combination therapy (Apalutamide + Carotuximab)Apalutamide-
Apalutamide monotherapyApalutamideAfter progression, subjects will crossover to combination therapy
Combination therapy (Apalutamide + Carotuximab)Carotuximab-
Primary Outcome Measures
NameTimeMethod
Radiographic progression free survival (rPFS) between patients receiving apalutamide and apalutamide + carotuximabFrom 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.

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.

Secondary Outcome Measures
NameTimeMethod
Overall radiographic response rate (ORR) in the overall populationFrom 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.

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

To determine the biochemical PFS (by PCWG3) in the overall populationFrom 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.

From the start of study treatment until documented progression, per Prostate Cancer Working Group 3, or death due to any cause.

Overall radiographic response rate (ORR) of the combination of apalutamide + carotuximabFrom 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.

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

Proportion of patients resistant to apalutamide benefit from the addition of carotuximabFrom 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.

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

To determine the radiographic progression free survival (rPFS) in the overall populationFrom 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.

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.

Incidence of Adverse events (grade 3 or higher) related to carotuximab and apalutamideFrom start of study treatment through 4 weeks on treatment

Grade 3 or above treatment related adverse events as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Trial Locations

Locations (3)

City of Hope

🇺🇸

Duarte, California, United States

Cedars-Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Huntsman Cancer Institute and Hospital

🇺🇸

Salt Lake City, Utah, United States

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