Clinical trial NCT03888612: Trial of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer
Official title: A Phase 1/2, Open-label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer Metastatic
Keywords: Metastatic Prostate Cancer
Castrate-Resistant
Prostate Cancer
mCRPC
adenocarcinoma of the prostate
bavdegalutamide
Lead sponsor: Arvinas Inc.
Sponsor class: INDUSTRY
First posted: 2019-03-25
Enrollment: 248
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase 1/2 dose escalation study to assess the safety and tolerability of ARV-110 in men with mCRPC who have progressed on prior approved systemic therapies for their castrate resistant disease (one of which must be enzalutamide or abiraterone).


Eligibility criteria: Inclusion Criteria:

Part A:

* Patients must be male and at least 18 years of age at the time of signing the informed consent.
* Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
* Patients must have progressed on at least 2 prior approved systemic therapies for CRPC (at least one must be abiraterone or enzalutamide).
* Patients with progressive mCRPC
* Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).

Part B:

* Patients must be male and at least 18 years of age at the time of signing the informed consent.
* Patients must present with histological, pathological, or cytological confirmed diagnosis of advanced or metastatic castration resistant adenocarcinoma of the prostate.
* Patients must have received at least one but no more than two prior second generation anti-androgen agents (e.g., enzalutamide or abiraterone) for CRPC.
* Patients must have received no more than one prior chemotherapy regimen in each of the following settings: castrate sensitive and castrate resistant prostate cancer.
* Patients must have ongoing ADT with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration).

Part B - Phase 2 Expansion Cohort Subgroup 4

* Patient has received only one prior AR second generation therapy (e.g., abiraterone or enzalutamide) either as treatment for CSPC or CRPC and no more than 1 regimen in CRPC setting.
* No prior chemotherapy

Exclusion Criteria:

Part A:

* Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
* Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
* Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
* Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.

Part B:

* Patients with known symptomatic brain metastases requiring steroids (above physiologic replacement doses)
* Major surgery (as defined by the Investigator) within 4 weeks of first dose of study drug.
* Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study
* Systemic anti cancer therapy within 2 weeks of first dose of study drug (6 weeks for bicalutamide, mitomycin C, or nitrosoureas and 4 weeks for abiraterone). Patients are ineligible if they received any other type of anti cancer agent (except agents to maintain castrate status) within 2 weeks before first dose of study drug.

Primary outcomes:
measure: Part A: Incidence of Dose Limiting Toxicities of ARV-110
timeFrame: 28 Days
measure: Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110
timeFrame: 28 Days
measure: Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110
timeFrame: 28 Days
measure: Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110
timeFrame: 12 Weeks
measure: Part B: Measurement of overall RECIST response rate accessing the anti-tumor activity of ARV-110
timeFrame: 12 Weeks
measure: Part B: To evaluate the clinical anti-tumor activity of ARV-110 in patients with mCRPC
timeFrame: 12 Weeks
Secondary outcomes:
measure: Part A: Anti-tumor activity based on the overall PSA response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Anti-tumor activity based on the overall RECIST response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Anti-tumor activity based on the progression free survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Anti-tumor activity based on the duration of response in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Anti-tumor activity based on the time to progression in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Anti-tumor activity based on the overall survival in the entire study population and in the subsets of patient based on the AR mutational status of their tumor.
timeFrame: 12 Weeks
measure: Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110
timeFrame: 28 Days
measure: Part B: Duration of response
timeFrame: 12 Weeks
measure: Part B: Overall survival
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Orange
country: United States
facility: Clinical Trial Site
state: California
city: San Francisco
country: United States
facility: Clinical Trial Site
state: California
city: New Haven
country: United States
facility: Clinical Trial Site
state: Connecticut
city: Altamonte Springs
country: United States
facility: Clinical Trial Site
state: Florida
city: Bonita Springs
country: United States
facility: Clinical Trial Site
state: Florida
city: Bradenton
country: United States
facility: Clinical Trial Site
state: Florida
city: Brandon
country: United States
facility: Clinical Trial Site
state: Florida
city: Cape Coral
country: United States
facility: Clinical Trial Site
state: Florida
city: Clearwater
country: United States
facility: Clinical Trial Site
state: Florida
city: Daytona Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Fleming Island
country: United States
facility: Clinical Trial Site
state: Florida
city: Fort Myers
country: United States
facility: Clinical Trial Site
state: Florida
city: Gainesville
country: United States
facility: Clinical Trial Site
state: Florida
city: Largo
country: United States
facility: Clinical Trial Site
state: Florida
city: Lecanto
country: United States
facility: Clinical Trial Site
state: Florida
city: Naples
country: United States
facility: Clinical Trial Site
state: Florida
city: New Port Richey
country: United States
facility: Clinical Trial Site
state: Florida
city: Ocala
country: United States
facility: Clinical Trial Site
state: Florida
city: Orange City
country: United States
facility: Clinical Trial Site
state: Florida
city: Orlando
country: United States
facility: Clinical Trial Site
state: Florida
city: Port Charlotte
country: United States
facility: Clinical Trial Site
state: Florida
city: Saint Petersburg
country: United States
facility: Clinical Trial Site
state: Florida
city: Sarasota
country: United States
facility: Clinical Trial Site
state: Florida
city: Spring Hill
country: United States
facility: Clinical Trial Site
state: Florida
city: Stuart
country: United States
facility: Clinical Trial Site
state: Florida
city: Tampa
country: United States
facility: Clinical Trial Site
state: Florida
city: Tavares
country: United States
facility: Clinical Trial Site
state: Florida
city: The Villages
country: United States
facility: Clinical Trial Site
state: Florida
city: Venice
country: United States
facility: Clinical Trial Site
state: Florida
city: Vero Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Wellington
country: United States
facility: Clinical Trial Site
state: Florida
city: West Palm Beach
country: United States
facility: Clinical Trial Site
state: Florida
city: Winter Park
country: United States
facility: Clinical Trial Site
state: Florida
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: New Orleans
country: United States
facility: Clinical Trial Site
state: Louisiana
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Detroit
country: United States
facility: Clinical Trial Site
state: Michigan
city: Omaha
country: United States
facility: Clinical Trial Site
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Trial Site
state: Nevada
city: New York
country: United States
facility: Clinical Trial Site
state: New York
city: Portland
country: United States
facility: Clinical Trial Site
state: Oregon
city: Dickson
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Franklin
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Gallatin
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Hendersonville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Hermitage
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Lebanon
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Murfreesboro
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Shelbyville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Smyrna
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Clinical Trial Site
state: Utah
city: Charlottesville
country: United States
facility: Clinical Trial Site
state: Virginia
Study officials:
References: