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PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

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ClinicalTrials.gov Identifier: NCT04556617
Recruitment Status : Recruiting
First Posted : September 21, 2020
Last Update Posted : March 25, 2021
Sponsor:
Information provided by (Responsible Party):
Plexxikon

Tracking Information
First Submitted Date  ICMJE September 14, 2020
First Posted Date  ICMJE September 21, 2020
Last Update Posted Date March 25, 2021
Actual Study Start Date  ICMJE September 21, 2020
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Phase 2a (both arms): Disease response as defined by at least one of the following: Objective response by modified RECIST v1.1, PSA response, or circulating tumor cell count (CTC) response. [ Time Frame: From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
  • Phase 1b (both arms): Incidence of dose-limiting-toxicities (DLTs) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days). ]
  • Phase 1b (both arms): Incidence of TEAEs that are related to treatment [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Radiographic progression-free survival (rPFS) (both arms, both phases) [ Time Frame: From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    Radiographic progression-free survival (PFS) will be calculated for each subject as the number of days from the first day of PLX2853 and combination agent(s) treatment (Cycle 1 Day 1) to the date of the first documented disease progression by either RECIST v.1.1 or on bone scan.
  • Time to PSA Progression (both arms, both phases) [ Time Frame: From 3 weeks of treatment (Cycle 2 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    PSA progression (defined per PCWG3 as a ≥25% increase and an absolute increase of ≥2 ng/mL above the nadir, which is confirmed by a second consecutive value obtained 3 or more weeks later).
  • Duration of PSA Response (both arms, both phases) [ Time Frame: From 3 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    Duration of PSA response will be calculated for each subject with a PSA response as the time from date of first documented, confirmed response (CR or PR) using PCWG3 until date of documented progression confirmed at least 3 weeks later, or death from any cause.
  • Overall Survival (OS) (both arms, both phases) [ Time Frame: From time of first dose until completion of long term follow-up, approximately 30 months. ]
    Overall survival (OS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment and combination agent(s) (Cycle 1 Day 1) to the date of death from any cause. If a subject is lost to follow-up, OS is censored at the date of last contact.
  • Incidence of all TEAEs (both arms, both phases) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]
  • Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms, both phases) [ Time Frame: From time of first dose of PLX2853 and combination agent(s) until 30 days from end of treatment. ]
  • PLX2853 PK parameter AUC0-24 (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    AUC from time zero extrapolated to 24 hours (AUC0-24)
  • PLX2853 PK parameter Cmax (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    Maximum observed concentration
  • PLX2853 PK parameter T1/2 (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    terminal elimination half-life (T1/2)
  • Best Overall Response (BOR) (both arms, both phases) [ Time Frame: From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    Best Overall Response (BOR) per RECIST v1.1 will be calculated for each subject with a minimum interval for confirmation of CR and PR of 4 weeks.
  • Duration of Response (DOR) (both arms, both phases) [ Time Frame: From 6 weeks of treatment (Cycle 3 Day 1; 21 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    Time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.
  • Time to first Symptomatic Skeletal-Related Event (SSRE) (both arms, both phases) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    Time to first Symptomatic Skeletal-Related Event (SSRE) defined as:
    • Use of radiation therapy to prevent or relieve skeletal symptoms.
    • Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). Radiologic documentation is required.
    • Occurrence of spinal cord compression. Radiologic documentation required.
    • Orthopedic surgical intervention for bone metastasis.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official Title  ICMJE A Multicenter, Open-Label, Parallel, Phase 1b/2a Study of PLX2853 in Combination With Abiraterone Acetate and Prednisone and Phase 1b/2a Study of PLX2853 in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Brief Summary The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in subjects with Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration-resistant Prostate Cancer
Intervention  ICMJE
  • Drug: PLX2853
    PLX2853 tablets
  • Drug: Olaparib
    Olaparib tablets
  • Drug: Abiraterone acetate
    Abiraterone acetate tablets
  • Drug: Prednisone
    Prednisone (or equivalent) tablets
Study Arms  ICMJE
  • Experimental: PLX2853 + Abiraterone Acetate + Prednisone

    Phase 1b (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 15 evaluable subjects with mCRPC will be enrolled.

    Phase 2a (PLX2853 + Abiraterone Acetate + Prednisone Combination): Up to 19 evaluable subjects with mCRPC will be enrolled.

    Interventions:
    • Drug: PLX2853
    • Drug: Abiraterone acetate
    • Drug: Prednisone
  • Experimental: PLX2853 + Olaparib

    Phase 1b (PLX2853 + Olaparib Combination): Up to 18 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.

    Phase 2a (PLX2853 + Olaparib Combination): Up to 58 evaluable subjects with homologous recombination repair (HRR) gene-mutated mCRPC will be enrolled.

    Interventions:
    • Drug: PLX2853
    • Drug: Olaparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 14, 2020)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 30, 2023
Estimated Primary Completion Date February 28, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥18 years at the time of signing informed consent.
  2. Histologically confirmed adenocarcinoma of the prostate with tumor tissue available for molecular analyses.
  3. Eastern Cooperative Oncology Group Performance Status 0 to 1.
  4. Adequate organ function as demonstrated following laboratory values.
  5. Fertile male subjects with female sexual partners must agree to use a highly effective method of birth control during the study and for 90 days after the last dose of study drug.
  6. Except as specified above for organ function, all drug-related toxicity from previous cancer therapy (including ongoing Abiraterone Acetate + Prednisone therapy if applicable) must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
  7. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

Exclusion Criteria:

  1. Prior exposure to a bromodomain inhibitor.
  2. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
  3. Clinically significant cardiac disease.
  4. Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption.
  5. Active known second malignancy with the exception of any of the following:

    • Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin.
    • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years.
    • Any other cancer from which the subject has been disease-free for ≥3 years.
  6. Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
  7. Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate in the study in the judgment of the Investigator.
  8. Receipt of any anti-cancer therapy prior to Cycle 1 Day 1 with less than protocol defined wash-out with the exception of Abiraterone Acetate (for subjects enrolling into Abiraterone Acetate Combination) and GnRH therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Paul Watkins 510-647-4151 Pwatkins@plexxikon.com
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04556617
Other Study ID Numbers  ICMJE PLX124-04
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Plexxikon
Study Sponsor  ICMJE Plexxikon
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Plexxikon
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP