The metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy
- Conditions
- metastatic castration-resistant prostate cancer (mCRPC)MedDRA version: 21.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001205-73-BE
- Lead Sponsor
- IMPACT Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 660
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.). 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) or completed at least 9 cycles and a maximum of 12 cycles of immediate prior treatment with docetaxel (2 weeks a cycle) with no evidence of PD after last docetaxel treatment.
For further details on this criteria please refer to the protocol.
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 (G-CSF), and other relevant medical support within 14 days before the administration of study drug):
a. Haemoglobin =9.0 g/dL.
b. Absolute neutrophil count (ANC) =1.5×109/L.
c. Platelet count =100×109/L.
d. Total bilirubin (TBIL) =1.5×institutional upper limit of normal (ULN) (for patients with Gilbert’s syndrome, total bilirubin (TBIL) =3xULN is required).
e. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =3×institutional ULN unless liver metastases are present in which cases, they must be =5×ULN.
f. Creatinine clearance =45 mL/min estimated using the Cockcroft-Gault equation.
g. International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) =1.5×ULN. It is not applicable for patients with Gilbert’s syndrome, whose enrollment should be discussed with the sponsor. The INR only applies to patients who do not receive therapeutic anti-coagulation.
10. Planned start of first dose of study drug 2 to 8 weeks after the last dose of docetaxel.
11. Patients have an Easte
Patients who meet any of the following criteria will be excluded from the study (* is for screening part 1, all criteria for screening part 2)
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 immediate prior treatment with 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method