Metastatic Castration-Resistant Prostate Cancer (mCRPC) MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification
Conditions
Interventions
Product Name: PLX2853
Product Code: PLX2853
Pharmaceutical Form: Tablet
Trade Name: ZYTIGA
Product Name: Abiraterone Acetate
Pharmaceutical Form: Tablet
INN or Proposed INN: ABIRATERONE ACETATE
CAS N
Sponsors
Plexxikon Inc.
Eligibility
Sex/Gender
Male
Inclusion 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. 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 + 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
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 the exception of GnRH therapy with less than protocol defined wash-out.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PLX2853 + abiraterone combination Phase 1b (Dose Escalation) The primary objective is as follows: - To evaluate the safety and tolerability of PLX2853 + abiraterone acetate + prednisone including dose limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone PLX2853 + abiraterone combination Phase 2a (Dose Expansion) The primary objective is as follows: - To evaluate the efficacy of PLX2853 + abiraterone acetate + prednisone at the RP2D in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone ;Secondary Objective: PLX2853 + abiraterone combination Phase 1b (Dose Escalation) The secondary objective is as follows: - To characterize the PK of PLX2853 and abiraterone and efficacy of PLX2853 combined with abiraterone acetate + prednisone in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone PLX2853 + abiraterone combination Phase 2a (Dose Expansion) The secondary objective is as follows: - To further characterize the safety and PK of PLX2853 and abiraterone when PLX2853 is combined with abiraterone acetate + prednisone in subjects with mCRPC who develop disease progression while currently receiving initial treatment with abiraterone acetate and prednisone ;Primary end point(s): PLX2853 + Abiraterone Acetate + Prednisone Combination Phase 1b – Primary Endpoint • Incidence of DLTs, TEAEs, changes in safety parameters, and unacceptable toxicities PLX2853 + Abiraterone Acetate + Prednisone Combination Phase 2a – Primary Endpoints Response as defined by any of the outcomes listed below. If any of these occur, the subject will be considered to have responded. • Objective response by per RECIST v1.1 with a minimum interval | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: • Radiographic progression free survival – Every 9 weeks through cycle 10, then every 12 weeks • Time to PSA progression – D1 of every cycle • Duration of PSA response – D1 of every cycle • Overall survival – all timepoints until death, lost to FU, or withdrawal of consent • Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities – all timepoints through 30 days after last dose or initiation of new anticancer treatment • PLX2853 PK parameters - C1D1, C1D2, C1D15, C2D1, C2D15, C3+D1 • BOR - Every 9 weeks through cycle 10, then every 12 weeks • DOR – D1 of every cycle until disease progression or death • Time to first Symptomatic Skeletal-Related Event: - all timepoints through 30 days after last dose or initiation of new anticancer treatment ;Secondary end point(s): PLX2853 + Abiraterone Acetate + Prednisone Combination (Phase 1b (Dose Escalation) and Phase 2a (Dose Expansion)): Secondary Endpoints • Radiographic progression-free survival (rPFS) • Time to PSA progression • Duration of PSA response • Overall survival defined as the time from the first dose of study drug to the date of death due to any cause • Incidence of TEAEs, changes in safety parameters, and unacceptable toxicities • PK parameters of PLX2853 and abiraterone and PLX2853 and olaparib following single and repeated dosing • BOR per RECIST v1.1 • DOR (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 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. | — |
Countries
United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Plexxikon Inc.
Outcome results
None listed