Trial of ARV-110 in Patients With Metastatic Castration Resistant Prostate Cancer

Prostate Cancer Metastatic Clinical Trial

— mCRPC  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03888612
• Other study ID #: ARV-110-mCRPC-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 1, 2019
• Est. completion date: November 30, 2024

Study information

• Verified date: May 2024
• Source: Arvinas Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: November 30, 2024
• Est. primary completion date: April 29, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• ARV-110
Part A: Daily oral dosages are predetermined by cohort review committee after the initial starting dose cohort after the first 28 days of treatment Part B: Daily oral dosage and schedule at a recommended Phase 2 dose based on data from Part A

Locations

Country	Name	City	State
United States	Clinical Trial Site	Altamonte Springs	Florida
United States	Clinical Trial Site	Bonita Springs	Florida
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Bradenton	Florida
United States	Clinical Trial Site	Brandon	Florida
United States	Clinical Trial Site	Cape Coral	Florida
United States	Clinical Trial Site	Charlottesville	Virginia
United States	Clinical Trial Site	Chicago	Illinois
United States	Clinical Trial Site	Clearwater	Florida
United States	Clinical Trial Site	Daytona Beach	Florida
United States	Clinical Trial Site	Detroit	Michigan
United States	Clinical Trial Site	Dickson	Tennessee
United States	Clinical Trial Site	Fleming Island	Florida
United States	Clinical Trial Site	Fort Myers	Florida
United States	Clinical Trial Site	Franklin	Tennessee
United States	Clinical Trial Site	Gainesville	Florida
United States	Clinical Trial Site	Gallatin	Tennessee
United States	Clinical Trial Site	Hendersonville	Tennessee
United States	Clinical Trial Site	Hermitage	Tennessee
United States	Clinical Trial Site	Largo	Florida
United States	Clinical Trial Site	Las Vegas	Nevada
United States	Clinical Trial Site	Lebanon	Tennessee
United States	Clinical Trial Site	Lecanto	Florida
United States	Clinical Trial Site	Los Angeles	California
United States	Clinical Trial Site	Murfreesboro	Tennessee
United States	Clinical Trial Site	Naples	Florida
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	New Haven	Connecticut
United States	Clinical Trial Site	New Orleans	Louisiana
United States	Clinical Trial Site	New Port Richey	Florida
United States	Clinical Trial Site	New York	New York
United States	Clinical Trial Site	Ocala	Florida
United States	Clinical Trial Site	Omaha	Nebraska
United States	Clinical Trial Site	Orange	California
United States	Clinical Trial Site	Orange City	Florida
United States	Clinical Trial Site	Orlando	Florida
United States	Clinical Trial Site	Port Charlotte	Florida
United States	Clinical Trial Site	Portland	Oregon
United States	Clinical Trial Site	Saint Petersburg	Florida
United States	Clinical Trial Site	Salt Lake City	Utah
United States	Clinical Trial Site	San Francisco	California
United States	Clinical Trial Site	Sarasota	Florida
United States	Clinical Trial Site	Shelbyville	Tennessee
United States	Clinical Trial Site	Smyrna	Tennessee
United States	Clinical Trial Site	Spring Hill	Florida
United States	Clinical Trial Site	Stuart	Florida
United States	Clinical Trial Site	Tampa	Florida
United States	Clinical Trial Site	Tavares	Florida
United States	Clinical Trial Site	The Villages	Florida
United States	Clinical Trial Site	Venice	Florida
United States	Clinical Trial Site	Vero Beach	Florida
United States	Clinical Trial Site	Wellington	Florida
United States	Clinical Trial Site	West Palm Beach	Florida
United States	Clinical Trial Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Arvinas Androgen Receptor, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Incidence of Dose Limiting Toxicities of ARV-110	First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug	28 Days
Primary	Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110	Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.	28 Days
Primary	Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.	28 Days
Primary	Part B: Measurement of PSA response rate per PCWG3 accessing anti-tumor activity of ARV-110	PSA response rate per PCWG3.	12 Weeks
Primary	Part B: Measurement of overall RECIST response rate accessing the anti-tumor activity of ARV-110	Overall RECIST response rate in patients with measurable disease at baseline.	12 Weeks
Primary	Part B: To evaluate the clinical anti-tumor activity of ARV-110 in patients with mCRPC	To evaluate the clinical anti-tumor activity (PSA response rate per PCWG3, Overall RECIST RR, rPFS, and PFS) of ARV-110 in patients with mCRPC in different subgroups of patients with mCRPC with predefined tumor genomic and molecular profiles or based on prior therapy.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the overall PSA response per PCWG3.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the overall RECIST response rate.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the time to event progression free survival.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the duration of response.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the time to progression.	12 Weeks
Secondary	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.	The anti-tumor activity of ARV-110 will be assessed by evaluating the overall survival.	12 Weeks
Secondary	Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).	28 Days
Secondary	Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter maximum concentration (Cmax).	28 Days
Secondary	Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter minimum concentration (Cmin).	28 Days
Secondary	Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)	28 Days
Secondary	Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC).	28 Days
Secondary	Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter maximum concentration (Cmax).	28 Days
Secondary	Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter minimum concentration (Cmin).	28 Days
Secondary	Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110	PK parameters will be assessed when applicable after a single dose and after multiple once and twice daily doses. Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)	28 Days
Secondary	Part B: Duration of response	From the date of first confirmed best overall response of CR or PR to the date of first progression per RECIST 1.1 or PCWG3, or death due to any cause without evidence of radiographic progression, whichever occurs first.	12 Weeks
Secondary	Part B: Overall survival	Time interval from the date of first ARV-110 dose to the date of death due to any cause.	12 Weeks