Castration-Resistant Prostate Cancer (CRPC) MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AT13387
Product Code: AT13387
Pharmaceutical Form: Injection
Trade Name: Zytiga
Product Name: Zytiga
Prod
Sponsors
Astex Pharmaceuticals Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Subjects who meet all of the following criteria will be eligible to participate in the study: 1. Have a histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology; Subjects who meet all of the following criteria will be eligible to participate in the study: 1. Have a histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology; 2. Have received prior castration by orchiectomy and/or LHRH agonist with or without antiandrogen and documented serum testosterone 18 years of age; 4. Have Eastern Cooperative Oncology Group (ECOG) performance Status =2; 5. Have not had androgen receptor (AR) antagonist treatment in the 6 weeks prior to the first dose of study drug; 6. Have been receiving abiraterone acetate therapy with a steroid for =1 month. Only subjects tolerating abiraterone acetate 1000 mg at screening will be eligible to participate in the study; 7. Have documented disease progression on abiraterone acetate defined by 1 or more of the following criteria: • PSA progression according to PCWG2 criteria with 3 consecutive rising PSA measurements, all collected at least 1 week apart; • Radiographic progression in soft tissue or bone by modified RECIST 1.1 for subjects with measurable disease; or • Bone disease progression defined by 2 or more new lesions on 2 consecutive bone scans in the absence of falling PSA; 8. Have CTC count >5 cells/7.5 mL at baseline (for Part A only); 9. Have adequate bone marrow function, defined as absolute neutrophil count >1.5 K/µL and platelet count >100 K/µL; 10. Have adequate hepatic function, defined as bilirubin =1.5 × ULN, ALT and aspartate transaminase (AST) =2.5 × ULN (ALT and AST =5 × ULN, if liver metastases are present); 11. Have adequate renal function, defined as creatinine =1.25 × ULN or creatinine clearance >50 mL/min; 12. Must be willing to provide pre-existing diagnostic or resected tumor samples, such as formalin-fixed, paraffin-embedded sections or slides, if this material exists. If pre-existing samples are not available, a sample must be obtained during screening; 13. Subjects and their female partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months following the last dose of study drug. Effective contraception includes methods such as oral contraceptives, double-barrier method (condom plus spermicide or diaphragm) or abstaining from sexual intercourse; and 14. Must be willing and able to provide written informed consent and comply with the protocol and study procedures. 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 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 148
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria will be excluded from the study: 1. Prior anti-cancer treatment with any HSP90 inhibitor or histone deacetylase (HDAC) inhibitor compound; 2. Have received chemotherapy within 4 weeks prior to the first dose of study drug; 3. Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug and single fraction radiotherapy within 2 weeks prior to the first dose of study drug; 4. Hypersensitivity to AT13387 or other components of the drug product; 5. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug; 6. Poor medical risk because of other systemic diseases or active uncontrolled infections; 7. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors which, in the Investigator’s opinion, could compromise the subject’s safety, interfere with the metabolism of AT13387, or compromise the integrity of the study outcomes; 8. Abnormal LVEF (450 msec after correction of any electrolyte imbalance and confirmation of QTc by triplicate measurement; 9. Prior malignancy except for adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder cancer, or other cancer from which the subject has been disease-free for at least 3 years; 10. Known symptomatic brain or CNS involvement such as a result of cord compression; 11. Contraindication to the use of corticosteroids or history of pituitary or adrenal dysfunction; 12. Prior dose reductions of abiraterone acetate as a result of increased transaminases; or 13. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: • To assess the safety and tolerability (incidence and severity of adverse events [AEs]) of the combination of AT13387 and abiraterone acetate and to select the most promising treatment regimen for the combination in subjects with castration-resistant prostate cancer (CRPC) who are no longer responding to treatment with abiraterone acetate alone, based on the overall assessment of safety and antitumor activity. Part B: • To assess and compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2] recommendations) between single-agent AT13387 and the combination of AT13387 plus abiraterone acetate in subjects who are no longer responding to treatment with abiraterone acetate alone. ; Secondary Objective: Part A: • To assess pharmacokinetic interactions between AT13387 and abiraterone; • To assess progression-free survival (PFS) per PCWG2 recommendations and overall survival (OS); and • To assess the androgen receptor (AR) depletion in circulating tumor cells (CTCs) and/or tumor tissue. Part B: • To assess and compare the safety of AT13387 alone and in combination with abiraterone acetate in CRPC; • To assess and compare pharmacodynamic markers of AR depletion and other client protein depletion in CTCs and/or tumor tissue in the 2 arms; and • To assess and compare PFS and OS in the 2 arms. ; Primary end point(s): Part A: The co-primary endpoints for the comparison between the 2 AT13387 regimens are as follows: • Incidence and severity of AEs and DLTs using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 to assess safety and • Response rate assessed based on achieving any one or more of the following: | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: • Pharmacokinetic parameters (maximum concentration [Cmax], area under the curve [AUC], and other secondary pharmacokinetic parameters) of AT13387 and abiraterone; • Depletion of AR and other client proteins in CTCs and/or in tumor tissue to assess biological activity and pharmacodynamics; • PFS (progression defined per PCWG2 recommendations); and • OS. Part B: • Clinical Benefit Rate: CR + PR + stable disease (SD) =24 weeks; • Incidence and severity of AEs using NCI CTCAE version 4; ;Timepoint(s) of evaluation of this end point: At the end of Stage 2 (35 subjects per arm), at least 7 responses should be observed in either arm to declare positive antitumor activity in that arm. If both arms succeed in Stage 2, a total of at least 56 subjects per arm will be randomized in order to compare antitumor activity between the 2 arms. | — |
Countries
Canada, Spain, United Kingdom, United States
Contacts
Public ContactRoss Ezzati
Medpace Inc
Outcome results
None listed