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)
Conditions
Interventions
Product Name: Senaparib
Product Code: IMP4297
Pharmaceutical Form: Capsule
INN or Proposed INN: Senaparib
CAS Number: 1401682-78-7
Current Sponsor code: IMP4297
Concentration unit: mg milligram(s)
Con
Sponsors
IMPACT Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if all the following criteria are met (* is for screening part 1, all criteria for screening part 2) 1. Patients must voluntarily participate in this clinical study. Be willing and able to provide written informed consent form (ICF) prior to any study activity. 2. Male =18 years of age on the day of signing the ICF. 3. Patients must have histologically or cytologically confirmed prostate adenocarcinoma. 4. Patients must have received and failed at least one novel hormonal agent (NHA, such as abiraterone, enzalutamide, etc.) before or in mCRPC stage. In addition, patients are allowed to have received and failed up to one novel hormonal therapy in mCRPC stage. Treatment failure is judged by the investigator. 5. Patients confirmed by investigator to be at mCRPC stage when starting the immediate prior treatment with docetaxel. Metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI. Metastatic lesions do not include disease spread to local pelvic lymph nodes or local disease recurrence (e.g., bladder and rectum). 6. Surgically or medically castrated, with serum testosterone levels of =50 ng/dL (=1.73 nmol/L). If the patient is being treated with LHRH agonists/antagonists (patient who have not undergone orchiectomy), this therapy must be continued throughout the study. 7. Completed at least 6 cycles and a maximum of 8 cycles of immediate prior treatment with docetaxel (3 weeks a cycle) with no evidence of PD after last docetaxel treatment. The investigator must check whether the patient has PD according to the following four criteria, taking the baseline of docetaxel treatment as reference (if there is no radiographic tumor evaluation at baseline, the earliest tumor assessment after the first dose of docetaxel will serve as reference). Patients cannot be enrolled if they meet any of the four criteria for PD. a. Radiographic soft-tissue lesions progression according to RECIST v1.1. b. Radiographic bone progression according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Bone progression= appearance of 2 or more new lesions (only positivity on the bone scan defines metastatic disease to bone). Ambiguous results will be confirmed by other imaging modalities (e.g., CT or MRI). c. PSA progression according to PCWG3 criteria. PSA progression is defined as: PSA progression =25% increase and =2 ng/mL increase from baseline of docetaxel treatment beyond 12 weeks, and which is confirmed by a second value =3 weeks later. d. Clinical PD judged by investigator, including but not limited to skeletal-related events (SREs, e.g., asymptomatic or symptomatic fractures, surgery or radiation therapy to bone, or spinal cord compression), tumor related pain progression and other tumor related symptoms or signs. 8. Documented germline/somatic mutation in at least one of the homologous recombination repair genes, including BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) assessed by central laboratory using validated Next-Generation Sequencing (NGS) test from blood samples. 9. Patients have adequate organ functions, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony- stimulating factor
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from the study (* is for screening part 1) 1. *Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT). 2. *Prior treatment with a polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including Senaparib. 3. *In mCRPC stage, any prior systemic therapy except for docetaxel, NHA or necessary ADT with LHRH agonists/antagonist for mCRPC. 4. *Patients with a known hypersensitivity to Senaparib or any of the component of Senaparib. 5. Patients who have other new malignancies within 2 years prior to the first dose of Senaparib will be excluded, except for radically treated basal or squamous cell skin cancer. Patients with other malignancies which have been treated with no relapse within 2 years can be enrolled. 6. Initiating bisphosphonate/denosumab therapy or adjusting bisphosphonate/denosumab dose/regimen within 28 days prior to the first dose of study drug. Patients on a stable bisphosphonate/denosumab regimen are eligible and may continue. 7. Patients who have received chemotherapy (except for docetaxel), targeted therapy, immunotherapy, endocrine therapy (except for necessary ADT with LHRH agonists/antagonist for mCRPC), anti-tumor Chinese herbal medicine or proprietary Chinese medicine treatment or other anti-cancer systemic treatment within 5 half-lives or 28 days (whichever is longer), prior to the first dose of study drug. 8. Patients who have any acute toxicities due to prior chemotherapy and/or radiotherapy that are >2 Grade per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 with the exception of alopecia. 9. Patients who have participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of study drug. For investigational drugs, the washout period should be 5 half-lives or 28 days whichever is longer. 10. Patients who have received strong inhibitors/inducers of CYP3A4 which cannot be discontinued 21 days prior to the first dose of study drug and withheld throughout the study drug treatment. Patients received phenobarbital/enzalutamide will require a 5-week washout prior to the first dose of study drug. 11. Patients who have undergone a major surgery or radical radiotherapy within 28 days prior to the first dose of study drug, or have undergone a palliative radiotherapy within 14 days prior to the first dose of study drug. 12. *Patients with MDS or AML, or with clinical features suggestive of MDS or AML. 13. Patients with serious acute or chronic infections. 14. Patients who have acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of study drug; patients who have congestive heart failure (New York Heart Association [NYHA] Classification Class =II); patients who have severe or uncontrolled hypertension, arrhythmia. 15. Patients with known and symptomatic brain metastasis. Patients with asymptomatic, treated, stable brain metastases without steroids for at least 28 days are eligible for study entry. A radiographic imaging to confirm the absence of brain metastases is not required. 16. Patients with symptomatic or impending spinal cord compression, unless appropriately treated for this and clinically stable and asymptomatic for 28 days prior to the first dose of study drug. 17. Patients who are unable to swallow a whole caps
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the impact of Senaparib maintenance on radiographic progression free survival (rPFS), compared with the placebo, in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy assessed by Blinded Independent Central Review (BICR);Secondary Objective: To evaluate the impact of Senaparib maintenance on rPFS, assessed by investigator, rPFS in BRCA1, BRCA2 or ATM mutation positive patients assessed by BICR, time to prostate-specific antigen (PSA) progression, time to pain progression, time to the first symptomatic skeletal related events (SSRE), radiographic response rate, PSA response rate, second progression (PFS2), overall survival (OS), safety, compared with the placebo. To characterize the pharmacokinetics (PK) of Senaparib based on a population PK (PopPK) modeling approach.;Primary end point(s): rPFS assessed by BICR rPFS is defined as the time from randomization to the date of first radiographic disease progression (PD) or death from any cause, whichever occurs first. Radiographic PD will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.;Timepoint(s) of evaluation of this end point: At the time when around 115 rPFS events are collected. DB lock planed May2021, Analysis Plan 1-2 month after DB lock. just a prediction. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) rPFS assessed by the investigator; 2) rPFS in BRCA1, BRCA2 or ATM mutation positive patients assessed by BICR; 3) Time to PSA progression 4) Time to pain progression 5) Time from randomization to the first SSRE 6) Objective response rate (ORR) according to RECIST v1.1 assessed by BICR 7) ORR according to RECIST v1.1 assessed by the investigator 8) PSA response rate 9) Second progression (PFS2) 10) Overall survival (OS) 11) Safety: Adverse events (AEs), vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory tests (including hematology, serum chemistry, urinalysis, and coagulation parameters) 12) PK characteristics of Senaparib based on PopPK modeling approach, with the available data;Timepoint(s) of evaluation of this end point: At the time when around 115 rPFS events are collected. DB lock planed May2021, Analysis Plan 1-2 month after DB lock. just a prediction. | — |
Countries
Australia, Belgium, France, Germany, Italy, Netherlands, Spain, Switzerland, Taiwan, United States
Contacts
Public ContactYunru Chen
IMPACT Therapeutics, Inc.
Outcome results
None listed