Clinical Trials /

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

NCT04556617

Description:

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)

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: PLX124-04
  • NCT ID: NCT04556617

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
PLX2853PLX2853 + Abiraterone Acetate + Prednisone
OlaparibPLX2853 + Olaparib
Abiraterone acetatePLX2853 + Abiraterone Acetate + Prednisone
PrednisonePLX2853 + Abiraterone Acetate + Prednisone

Purpose

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)

Trial Arms

NameTypeDescriptionInterventions
PLX2853 + Abiraterone Acetate + PrednisoneExperimentalPhase 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.
  • PLX2853
  • Abiraterone acetate
  • Prednisone
PLX2853 + OlaparibExperimentalPhase 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.
  • PLX2853
  • Olaparib

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description: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).
Measure: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.
Safety Issue:
Description: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.
Measure:Overall Survival (OS) (both arms, both phases)
Time Frame:From time of first dose until completion of long term follow-up, approximately 30 months.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure:PLX2853 PK parameter AUC0-24 (both arms, both phases)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:AUC from time zero extrapolated to 24 hours (AUC0-24)
Measure:PLX2853 PK parameter Cmax (both arms, both phases)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:Maximum observed concentration
Measure:PLX2853 PK parameter T1/2 (both arms, both phases)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:terminal elimination half-life (T1/2)
Measure: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.
Safety Issue:
Description: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.
Measure: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.
Safety Issue:
Description:Time from date of first documented, confirmed response using RECIST v1.1 and PCWG3 until date of documented progression or death from any cause.
Measure: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.
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Plexxikon

Trial Keywords

  • PLX2853
  • Metastatic Castration-resistant Prostate Cancer
  • Olaparib
  • Abiraterone Acetate
  • Adenocarcinoma
  • Prostate Cancer

Last Updated

October 6, 2020