Trial of ARV-110 and Abiraterone in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

Prostate Cancer Metastatic Clinical Trial

Official title:

A Phase 1b Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-110 in Combination With Abiraterone in Patients With Metastatic Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05177042
• Other study ID #: ARV-110-mCRPC-103
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 1, 2022
• Est. completion date: December 31, 2025

Study information

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

Clinical Trial Summary

Phase 1b study to assess the combination of ARV-110 and abiraterone in patients with metastatic prostate cancer with rising PSA values on abiraterone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: December 31, 2025
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate.

2. Ongoing treatment with stable doses of abiraterone (on an empty stomach) and a concomitant corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) or for metastatic castration sensitive prostate cancer (mCSPC) until Cycle 1, Day 1 (C1D1).

3. Recent PSA values must demonstrate:

1. Rising PSAs at least 16 weeks after initiation of abiraterone

2. At least 2 PSA values that are higher than the PSA nadir on abiraterone, measured at a minimum of 1 week apart . The screening PSA for this study may be used as the 2nd PSA value.

4. No known radiographic evidence of disease progression while receiving abiraterone and clinically benefitting at the time of consent. If there is radiographic disease progression during screening, the patient may be considered eligible if, in the judgement of the investigator, the patient is clinically benefitting from abiraterone.

5. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (surgical or medical castration).

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Previously treated with enzalutamide, apalutamide, darolutamide or experimental therapies (e.g., protein degraders or inhibitors) directed at the AR.

2. Treatment with any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other than GnRH agonists within 28 days of the start of treatment on protocol.

3. Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow.

4. Patients taking agents that are either a) sensitive P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) substrates, or CYP3A4 substrates, b) P-gp, BCRP, CYP3A4, or CYP2D6 substrates that have a narrow therapeutic index, c) strong CYP3A4 inhibitors or inducers, or d) any other prohibited and/or restricted medications described in the protocol.

5. Major surgery (as judged by the Investigator) within 4 weeks of first dose of study drug.

6. Untreated brain metastases or brain metastases requiring steroids

7. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.

8. Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class II, III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic disease.

9. Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bifascicular block), or ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade =2, atrial fibrillation of any grade (Grade =2 in the case of asymptomatic lone atrial fibrillation)..

10. Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).

11. Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.

12. Active inflammatory gastrointestinal disease, uncontrolled chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Gastroesophageal reflux disease is allowed except for if under treatment with proton pump inhibitors.

13. Patients with Child Pugh C.

14. Patients with electrolyte imbalances of hypokalemia, hypomagnesemia, and/or hypocalcemia.

15. Patients with QTcF =470 msec.

Related Conditions & MeSH terms

• Prostate Cancer Metastatic
• Prostatic Neoplasms

Intervention

Drug:
• ARV-110 in Combination with Abiraterone
ARV-110 oral tablets in combination with abiraterone and a corticosteroid administered daily in 28 day cycles

Locations

Country	Name	City	State
Canada	Clinical Trial Site	Montreal	Quebec
Canada	Clinical Trial Site	Toronto	Ontario
Canada	Clinical Trial Site	Vancouver	British Columbia
France	Clinical Trial Site	Caen
France	Clinical Trial Site	Paris
France	Clinical Trial Site	Villejuif
United Kingdom	Clinical Trial Site	Cardiff	Wales
United Kingdom	Clinical Trial Site	London	England
United Kingdom	Clinical Trial Site	Preston
United States	Clinical Trial Site	Boston	Massachusetts
United States	Clinical Trial Site	Charlottesville	Virginia
United States	Clinical Trial Site	Columbus	Ohio
United States	Clinical Trial Site	Fort Myers	Florida
United States	Clinical Trial Site	Myrtle Beach	South Carolina
United States	Clinical Trial Site	Nashville	Tennessee
United States	Clinical Trial Site	New Haven	Connecticut
United States	Clinical Trial Site	Portland	Oregon
United States	Clinical Trial Site	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Arvinas Androgen Receptor, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities of ARV-110 in combination with abiraterone	Dose limiting toxicities in first 4 weeks of the study combination treatment characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), timing, seriousness, and relationship to study drug	4 weeks
Primary	Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-110 in combination with abiraterone	Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination	35 days after subject discontinues study treatment
Primary	Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-110 in combination with abiraterone	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v 5.0), and timing.	35 days after subject discontinues study treatment
Primary	Recommended Phase 2 dose (RP2D)/schedule for the combination	Dose limiting toxicities in first 4 weeks of the study combination treatment will be assessed to determine the dose of ARV-110 and abiraterone associated with acceptable safety and tolerability.	4 weeks