Clinical trial NCT04822961: Senaparib in mCRPC Patients With Homologous Recombination Repair Gene Alterations After Docetaxel Treatment
Official title: A Randomized, Double-Blinded, Placebo-Controlled, Multicenter, Phase II Study to Evaluate Senaparib in mCRPC Patients With Homologous Recombination Repair Gene Alterations After Docetaxel Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: mCRPC
Lead sponsor: Impact Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-30
Enrollment: 285
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-Blinded, Placebo-Controlled
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of Senaparib in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations after docetaxel treatment

Detailed description: This is a randomized, double-blinded, placebo-controlled, multicenter, Phase II study in mCRPC patients with HRR gene alterations after docetaxel therapy to evaluate the anti-tumor activity and safety of Senaparib.

Eligibility criteria: Inclusion Criteria:

1. Patients must voluntarily participate in this clinical study. Be willing 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. 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.
5. 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).
6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Male patients must use a condom during treatment and for 3 months after the last dose of study drug when having sexual intercourse with a woman of childbearing potential. Female partners of male patients should also use an acceptable method of contraception if they are of childbearing potential.

Exclusion Criteria:

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. Patients with a known hypersensitivity to Senaparib or any of the component of Senaparib.
4. 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.
5. 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.
6. Patients with MDS or AML, or with clinical features suggestive of MDS or AML.
7. Patients with serious acute or chronic infections.
8. Patients who have received a live virus or bacterial or RNA vaccination within 28 days prior to the first dose of study drug.
9. Patients are unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.

Primary outcomes:
measure: rPFS assessed by BICR
timeFrame: 80 weeks
Secondary outcomes:
measure: rPFS assessed by BICR
timeFrame: 80 weeks
measure: Time to pain progression
timeFrame: 80 weeks
measure: Time from randomization to the first SSRE
timeFrame: 80 weeks
measure: OS
timeFrame: 80 weeks
measure: PFS2
timeFrame: 80 weeks
measure: Time to pain progression
timeFrame: 80 weeks
measure: Time from randomization to the first SSRE
timeFrame: 80 weeks
measure: OS
timeFrame: 80 weeks
measure: rPFS assessed by the investigator
timeFrame: 80 weeks
measure: Time to PSA progression
timeFrame: 80 weeks
measure: Objective response rate (ORR) according to RECIST v1.1 assessed by BICR
timeFrame: 80 weeks
measure: Objective response rate (ORR) according to RECIST v1.1 assessed by investigator
timeFrame: 80 weeks
measure: PSA response rate according to PCWG3 criteria assessed by central laboratory
timeFrame: 80 weeks
measure: Safety endpoints
timeFrame: 80 weeks
measure: Cmax
timeFrame: 80 weeks
Other outcomes:
Locations:
city: Binghamton
country: United States
facility: Our lady of Lourdes Urology
state: New York
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Melbourne
country: Australia
facility: Cabrini Hospital
city: Sydney
country: Australia
facility: Macquarie University Hospital
city: Tugun
country: Australia
facility: John Flynn Hospital
city: Shanghai
country: China
facility: IMPACT Therapeutics Inc.
state: Shanghai
Study officials:
References: