ProSTAR: A Study Evaluating CPI-1205 in Patients With Metastatic Castration Resistant Prostate Cancer
- Conditions
- Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Interventions
- Registration Number
- NCT03480646
- Lead Sponsor
- Constellation Pharmaceuticals
- Brief Summary
This was an open-label Phase 1b/2 study involving oral administration of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone in male patients with metastatic Castration-Resistant Prostate Cancer. The study was designed to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D) based on the safety, tolerability, pharmacokinetic, and efficacy profiles of CPI-1205 in combination with either enzalutamide or abiraterone/prednisone.
Following the determination of the MTD and RP2D, the study proceeded to Phase 2. Patients in Phase 2 received CPI-1205 at the RP2D in combination with either enzalutamide or abiraterone/prednisone versus either enzalutamide or abiraterone/prednisone as a control arm.
- Detailed Description
Study CPI-1205-201 was a Phase 1b/2, multi-center, open-label study of CPI-1205 alone and with cobicistat in subjects with mCRPC in combination with either enzalutamide or abiraterone/prednisone. The study initially had two phases: a Phase 1 dose-finding, dose-escalation study intended to establish the Recommended Phase 2 Dose (RP2D) of CPI-1205 for the Phase 2 portion.
The study underwent three amendments.
PHASE 1b In the Phase 1b dose-escalation phase and prior to Amendment 2, subjects were enrolled into Phase 1b dose level CPI-1205 PO three times daily (TID) + enzalutamide or abiraterone/prednisone.
In Amendment 2, new subjects were enrolled into cohorts including:
Dose-escalating CPI-1205 PO twice daily (BID) + fixed-dose cobicistat PO BID + enzalutamide Dose-escalating CPI-1205 PO BID + fixed-dose cobicistat PO BID + abiraterone/prednisone In Amendment 3, Phase 1b expansion cohort(s) were added in the heavily pretreated population (HPEC). An HPEC began enrollment if 0 out of 3 or 1 out of 6 subjects treated with a specific regimen (i.e., CPI-1205 with or without cobicistat, in combination with enzalutamide or abiraterone) at a given dose level during Phase 1b dose escalation experienced a dose-limiting toxicity (DLT).
Following determination of the maximum tolerated dose (MTD) in each of the CPI-1205 BID + cobicistat combinations (and possibly in the CPI-1205 TID combination) and after evaluation of the BID cohorts without cobicistat (if applicable), only one of the CPI-1205 dosing schedules was selected as the RP2D for each combination. One or both combinations proceeded to Phase 2 after consideration of pharmacokinetic (PK) and pharmacodynamic (PD) results, data from the HPEC(s), and safety data.
PHASE 2 If only one partner product was chosen for Phase 2, the study proceeded as an open-label randomized Phase 2 trial, with subjects randomized to either the combination arm (CPI-1205 at the RP2D \[with or without cobicistat\] in combination with enzalutamide or abiraterone/prednisone) or the control arm (enzalutamide or abiraterone/prednisone as monotherapy). If both partner products were chosen, the second Phase 2 was either a second open-label randomized trial or a single-arm Phase 2 trial (following a Simon's 2-stage design). The design of the second trial was determined by the Sponsor based on preliminary efficacy and PK.
CPI-1205 was administered orally TID or BID (as of Amendment 2). Cobicistat dosing began with one dose the evening prior to Day 1 of CPI-1205 and continued PO BID starting on Day 1. Enzalutamide and abiraterone were given PO once daily, and prednisone was given PO BID (or at the investigator's discretion).
Successive 28-day treatment cycles were repeated without planned breaks, as long as the combination was well tolerated, until radiographic disease progression, unequivocal clinical progression, or planned initiation of another systemic treatment. Investigators could continue treatment in subjects with progression in one site if other lesions might benefit. Subjects in the control arm who progressed had the option to cross over to the combination arm, provided they met eligibility criteria.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 175
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza CPI-1205 CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza Cobicistat CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi + Enza Enzalutamide CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Enzalutamide 160 mg PO QD (28-day cycles) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred CPI-1205 CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred Cobicistat CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred Abiraterone CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 400 mg BID + Cobi+ Abi/Pred Prednisone CPI-1205 400 mg BID in combination with Cobicistat 150 mg PO BID and Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza CPI-1205 CPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle) Phase 1b Dose Escalation: CPI-1205 800 mg TID + Enza Enzalutamide CPI-1205 800 mg TID in combination with Enzalutamide 160 mg PO QD (28-day cycle) Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred CPI-1205 CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred Abiraterone CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b Dose Escalation: CPI-1205 800 mg TID + Abi/Pred Prednisone CPI-1205 800 mg TID in combination with Abiraterone 100 mg PO QD and Prednisone 5 mg PO BID (28-day cycle) Phase 1b HPEC: CPI-1205 800 mg TID + Enza CPI-1205 CPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles) Phase 1b HPEC: CPI-1205 800 mg TID + Enza Enzalutamide CPI-1205 800 mg TID highly pretreated expansion cohort (HEPC) in combination with Enzalutamide 160 mg PO QD (28-day cycles) Phase 2 Randomized Controlled Group: Enza Enzalutamide Drug: Enzalutamide 160mg PO QD (28-day cycles) Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza CPI-1205 CPI-1205 (at Recommended Phase 2 Dose \[RP2D\]) in combination with Drug: Enzalutamide 160 mg PO QD Phase 2 Randomized at RP2D: CPI-1205 800 mg TID + Enza Enzalutamide CPI-1205 (at Recommended Phase 2 Dose \[RP2D\]) in combination with Drug: Enzalutamide 160 mg PO QD Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred CPI-1205 CPI-1205 at 800 mg TID (Recommended Phase 2 Dose \[RP2D\]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles) Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred Abiraterone CPI-1205 at 800 mg TID (Recommended Phase 2 Dose \[RP2D\]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles) Phase 2 Single Arm at RP2D: CPI-1205 800 mg TID + Abi/Pred Prednisone CPI-1205 at 800 mg TID (Recommended Phase 2 Dose \[RP2D\]) 800 mg TID in combination with Abiraterone 1000 mg PO QD and Prednisone 5 mg PO BID (28-day cycles)
- Primary Outcome Measures
Name Time Method Efficacy: Best Objective Response Rate Percent by Treatment Group Up to 2 years [or until disease progression or unacceptable toxicity] Best overall response rate (%) defined as complete response (CR) + partial response (PR) divided by the total number of subjects as assessed by Investigator. The response assessment was performed per Prostate Cancer Working Group 3 (PCWG3) based on modifications of the RECIST 1.1 criteria. Per RECIST 1.1, a CR was assessed when all target lesions disappeared (any pathological lymph node must have reduction in short axis to \<10 mm) in the post-baseline scan. A PR was assessed when there was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Efficacy: Percentage (%) of Subjects With PSA30 2 years [or until progressive disease or unacceptable toxicity] The number of subjects who had a confirmed reduction of 30% of prostate-specific antigen (PSA30) from baseline
Efficacy: Percentage (%) of Subjects With PSA50 2 years [or until progressive disease or unacceptable toxicity] The number of subjects who had a confirmed reduction of 50% of prostate-specific antigen (PSA50) from baseline
Efficacy: Composite Response Rate (%) for Phase 2 Randomized and Phase 2 Single-arm Treatment Groups Up to 2 years [or until progressive disease or unacceptable toxicity] Subjects who had a circulating tumor cell of 30% (CTC 30%) or an objective response rate divided by the number of evaluable subjects
- Secondary Outcome Measures
Name Time Method Efficacy: Best Responses by Treatment Group Up to 2 years [or until disease progression or unacceptable toxicity] Best overall response defined as complete response (CR), partial response (PR); stable disease (SD); progressive disease (PD); and unknown/missing for the Phase 1b dose-escalation group, the Phase 1b HPEC group, the Phase 2 randomized groups, crossover group and the Phase 2 single-arm group. Assessed by Investigator
Safety: Number of Participants With Treatment-emergent AEs Leading to Treatment Discontinuation Up to 2 years [or until clinical progression, radiographic disease progression, or until unacceptable toxicity] Treatment-emergent Adverse events (AEs) leading to subjects withdrawing from treatment
Trial Locations
- Locations (41)
Alaska Urological Institute
🇺🇸Anchorage, Alaska, United States
Beverly Hills Cancer Center (BHCC)
🇺🇸Beverly Hills, California, United States
John Wayne Cancer Inst.
🇺🇸Duarte, California, United States
UCLA
🇺🇸Los Angeles, California, United States
Rocky Mountain Cancer Centers
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Florida
🇺🇸Jacksonville, Florida, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Scroll for more (31 remaining)Alaska Urological Institute🇺🇸Anchorage, Alaska, United States