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

Study Overview
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Brief Summary
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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.

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

Conditions
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Castration-resistant Prostate Cancer

Intervention / Treatment
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* Drug: Apalutamide
* Drug: Carotuximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apalutamide monotherapy<br>After progression, subjects will crossover to combination therapy | Drug: Apalutamide<br>* Standard of care Apalutamide 240 mg administered orally and daily on Days 1-28 of every 28 day cycle<br>|
| Experimental: Combination therapy (Apalutamide + Carotuximab)<br> | Drug: Apalutamide<br>* Standard of care Apalutamide 240 mg administered orally and daily on Days 1-28 of every 28 day cycle<br>Drug: Carotuximab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Castration-resistant, CRPC