Clinical trial NCT05534646: Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer
Official title: Phase II Study of Apalutamide With Carotuximab in Metastatic, Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Castration-resistant Prostate Cancer
Keywords: Prostate cancer
Castration-resistant
CRPC
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Enviro Therapeutics, Inc.
First posted: 2022-09-09
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Radiographic progression free survival (rPFS) between patients receiving apalutamide and apalutamide + carotuximab
timeFrame: 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 outcomes:
measure: Incidence of Adverse events (grade 3 or higher) related to carotuximab and apalutamide
timeFrame: From start of study treatment through 4 weeks on treatment
measure: Overall radiographic response rate (ORR) of the combination of apalutamide + carotuximab
timeFrame: 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.
measure: Proportion of patients resistant to apalutamide benefit from the addition of carotuximab
timeFrame: 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.
measure: Overall radiographic response rate (ORR) in the overall population
timeFrame: 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.
measure: To determine the radiographic progression free survival (rPFS) in the overall population
timeFrame: 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.
measure: To determine the biochemical PFS (by PCWG3) in the overall population
timeFrame: 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.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute and Hospital
state: Utah
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Edwin Posadas, MD FACP
role: PRINCIPAL_INVESTIGATOR
References: