Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Metastatic Castration-resistant Prostate Cancer, PARP inhibitor, Homologous Recombination Deficiency, BRCA1/2 Mutation
Brief summary
The purpose of this study is to assess the efficacy of a PARP inhibitor, Pamiparib, in metastatic castration-resistant prostate cancer patients with homologous recombination deficiency or BRCA 1 or 2 somatic/germline mutation.
Detailed description
This is a single arm, open-label, single center, phase II trial, assessing the efficacy of a PARP inhibitor, Pamiparib, in 50 progressing metastatic castration-resistant prostate cancer patients with at least one line of androgen deprivation therapy or chemotherapy at the metastatic setting, and homologous recombination deficiency or BRCA 1 or 2 somatic or germline mutation.
Interventions
DRUGPamiparib
40 mg bid per os , 28 day cycle, number of cycles: until progression or unacceptable toxicity develops.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥18 years old, male 2. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma without neuroendocrine differentiation of the prostate. Mixed histology is accepted, except for small cell carcinoma. 3. Have a deleterious mutation in BRCA1/2 , or HRD score ≥ 9. 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 5. BPI\<4 6. Metastatic Castration-resistant Prostate Cancer (mCRPC): Presence of measurable target lesion according to RECIST criteria v1.1 7. Male subject has been surgically or medically sterilized and has serum testosterone level ≤1.73nmol/L. 8. Unsterilized male subject uses an acceptable method of contraception (defined as a barrier method with spermicide) to prevent pregnancy during the duration of the study and for 6 months after the last dose of Pamiparib. 9. Experienced disease progression after having received at least 1 prior next-generation androgen receptor-targeted therapies, for metastatic castration-resistant disease. 10. Capable of swallowing the whole capsule. 11. Subjects must have normal organ and bone marrow function at baseline, as defined below: Hemoglobin ≥ 9.0 g/dL at least 28 days after transfusion . Absolute neutrophil count ≥ 1.5 × 10\^9/L. Platelet count ≥ 100 × 10\^9/L. Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) specified. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase/alanine aminotransferase (ALT) serum glutamic pyruvic transaminase) ≤ 3 × the specified ULN, unless liver metastases are present, in which case it must be ≤ 5 × ULN. 12. Agree to sign informed consent form 13. Agree not to participate in other interventional trials during this trial.
Exclusion criteria
Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiologic Progression-free Survival (rPFS) | 3 years | Radiologic progression-free survival will be assessed from the time of the first dose to radiologic disease progression or death from any cause, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From enrollment to primary completion of study (up to approximately 3 years) | Proportion of patients in complete remission (CR) plus partial remission (PR) |
| Duration of Response (DOR) | From enrollment to primary completion of study (up to approximately 3 years) | Time from the start of the first assessment of the tumor as CR or PR to the first assessment of PD (Progressive Disease) or death from any cause. |
| Time to Response (TTR) | From enrollment to primary completion of study (up to approximately 3 years) | Time from initiation of treatment to first assessment of tumor as CR or PR. |
| Clinical Benefit Rate | 3 years | according to RECIST, is either complete response (CR), partial response (PR) or stable disease (SD) lasting for at least 16 weeks |
| Overall Survival (OS) | From enrollment to primary completion of study (up to approximately 3 years) | Time between the start of treatment and death from any cause |
| Adverse events | 3 years | Adverse events are graded according to the CTCAE V4.03 |
| Prostate Specific Antigen (PSA) Response Rate | From enrollment to primary completion of study (up to approximately 3 years) | Proportion of patients with a 50% decrease in PSA from baseline |
| Time to PSA Progression | From enrollment to primary completion of study (up to approximately 3 years) | Time from initiation of treatment to two consecutive 50% PSA increases from baseline level |
Other
| Measure | Time frame | Description |
|---|---|---|
| rPFS stratified by baseline HRD score (HRD score threshold is defined as 9) | 3 years | The rPFS is defined as the duration from Pamiparib initiation to radiologic disease progression or death from any cause, whichever comes first. |
| OS stratified by baseline HRD score (HRD score threshold is defined as 9) | 3 years | The OS is defined as the duration from Pamiparib initiation to any death. |
Countries
China
Contacts
Primary ContactFangjian Zhou, M.D.
Backup ContactYonghong Li, M.D.
Outcome results
None listed