Description:
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).
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
ARV-110-mCRPC-101
- NCT ID:
NCT03888612
Conditions
- Prostate Cancer Metastatic
Interventions
| Drug | Synonyms | Arms |
|---|
| ARV-110 | | ARV-110 |
Purpose
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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| ARV-110 | Experimental | Part A: Oral tablet(s), once or twice daily in 28 day cycles
Part B: Oral tablet(s), once or twice daily in 28 day cycles | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Part A: Incidence of Dose Limiting Toxicities of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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 |
Secondary Outcome Measures
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall PSA response per PCWG3. |
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall RECIST response rate. |
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the time to event progression free survival. |
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the duration of response. |
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the time to progression. |
| 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. |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | The anti-tumor activity of ARV-110 will be assessed by evaluating the overall survival. |
| Measure: | Part A: Concentration-time curve (AUC) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part A: Maximum concentration (Cmax) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part A: Minimum concentration (Cmin) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part A: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Part B: Concentration-time curve (AUC) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part B: Maximum concentration (Cmax) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part B: Minimum concentration (Cmin) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Part B: Time to maximum concentration (Tmax) for single and multiple dose of ARV-110 |
| Time Frame: | 28 Days |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Part B: Duration of response |
| Time Frame: | 12 Weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Part B: Overall survival |
| Time Frame: | 12 Weeks |
| Safety Issue: | |
| Description: | Time interval from the date of first ARV-110 dose to the date of death due to any cause. |
| Measure: | Part B: Duration on therapy |
| Time Frame: | 12 Weeks |
| Safety Issue: | |
| Description: | Time from first study treatment to last study treatment |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Arvinas Inc |
Trial Keywords
- Metastatic Prostate Cancer
- Castrate-Resistant
- Prostate Cancer
- mCRPC
- adenocarcinoma of the prostate
Last Updated
June 25, 2021
