A Phase I/II Open-Label, Dose-Escalation and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARV-766 in Patients With Metastatic Castration-Resistant Prostate Cancer
Study Identifier:
CJSB462A12101
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Recruitment Complete
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Study Summary
to evaluate the safety and efficacy of ARV-766 given by mouth in men with metastatic castration-resistant prostate cancer who have progressed on prior approved systemic therapies
To evaluate the safety and efficacy of ARV-766 in men with metastatic castration-resistant prostate cancer.
To evaluating the safety and tolerability of ARV-766, 2 doses (100 mg and 300 mg administered orally once daily in 28-day cycles) were selected for the phase 2 cohort expansion.
In part A (dose escalation), to assess safety and tolerability and select recommended phase 2 doses (RP2Ds);
in part B (cohort expansion), to evaluate the antitumor activity of the RP2Ds
Part C of this study will assess the addition of ARV-766 to abiraterone for the treatment of NHA-naïve mCRPC or mCSPC.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Prostate
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Male
Age
18+ years
Study Drug
Drug: Participant Group/ Arm Intervention/Treatment Experimental: Part A: ARV-766 Monotherapy (Dose Escalation)
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- Key Inclusion Criteria for Parts A, B, and C:
- Participants must be able to take oral medication without crushing, dissolving, or chewing tabletsHistological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostateProgression on approved systemic therapies for metastatic prostate cancer (at least one must be a second-generation androgen inhibitor, e.g., abiraterone, enzalutamide, darolutamide, apalutamide) (Parts A and B only)Progressive mCRPC (Parts A and B only) defined as:Serum testosterone levels <50 ng/dL (or ≤0.50 ng/mL or 1.73 nmol/L) using testosterone assays with a sensitivity of ≤30 ng/dL, within 28 days before study drug treatmentRadiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3)Disease progression on or following the most recent systemic therapyOngoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone analog or inhibitor, or orchiectomy (surgical or medical castration) (Parts A and B only)Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Metastatic castration resistant or sensitive prostate cancer with radiographic evidence of metastatic disease (soft tissue disease per modified RECIST 1.1 criteria or bone disease per PCWG3) (Part C)
Exclusion criteria
- Key Exclusion Criteria for Parts A, B, and C:
- Known symptomatic brain metastases requiring steroids (above physiologic replacement doses)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 or other low grade localized cancer. Eligibility for exception requires Sponsor approvalAny 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 III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic diseaseAny 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). 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). Anticoagulation (heparin/lovenox only) can be allowed if indicatedQTcF >480 msec at baseline based on ECGActive inflammatory gastrointestinal disease, chronic diarrhea, diverticulitis, or previous gastric resection or lap band surgeryParticipants taking sensitive BCRP and P-glycoprotein (P-gp) substrates or substrates with narrow therapeutic indices, strong CYP3A4 inhibitors and inducers, restricted medications described in the study protocol and the Investigator's Brochure, and additionally for Part C, CYP2D6 substrates with a narrow therapeutic indexInadequate bone marrow function defined as follows (with no transfusion of blood products or use of hematopoietic growth factors in the 28 days prior to start of therapy):Absolute neutrophil count <1,500/mm3 or <1.5 × 109/LPlatelets <100,000/mm3 or <100 × 109/LHemoglobin <9 g/dLInadequate renal function defined as estimated creatinine clearance (Clcr) ≤60 mL/min using Cockcroft-Gault formula or eGFR ≤60 mL/min/1.73m3 using the CKD-EPI equationElectrolyte imbalances of clinically significant hypokalemia, hypomagnesemia, and/or hypocalcemia (Part C only)Inadequate liver function defined as:Total serum bilirubin >1.5× upper limit of normal (ULN) unless the participant has documented Gilbert syndromeAspartate aminotransferase (AST) and alanine aminotransferase (ALT) of >2.5× ULN if there is NO liver involvement secondary to tumor OR >5.0× ULN if there is liver involvement secondary to tumorPrior treatment with a second-generation NHA such as abiraterone, enzalutamide, darolutamide, or apalutamide (Part C only). Note: prior chemotherapy is allowed.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruitment Complete
Condition(s) Treated at Site
Prostate