Senaparib in mCRPC Patients With Homologous Recombination Repair Gene Alterations After Docetaxel Treatment

mCRPC Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04822961
• Other study ID #: IMP4297-202
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 31, 2021
• Est. completion date: August 2024

Study information

• Verified date: December 2021
• Source: Impact Therapeutics, Inc.
• Contact: xingxing Zhang
• Phone: +862168411121
• Email: xingxing.zhang[@]impacttherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 285
• Est. completion date: August 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• mCRPC

Intervention

Drug:
• Placebo
Senaparib-matched placebo capsules
• Senaparib
20 mg capsules

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane
Australia	Cabrini Hospital	Melbourne
Australia	Macquarie University Hospital	Sydney
Australia	John Flynn Hospital	Tugun
China	IMPACT Therapeutics Inc.	Shanghai	Shanghai
United States	Our lady of Lourdes Urology	Binghamton	New York

Sponsors (1)

Lead Sponsor	Collaborator
Impact Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rPFS assessed by BICR	To evaluate the impact of Senaparib on radiographic progression free survival (rPFS), compared with the placebo, in metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy assessed by Blinded Independent Central Review (BICR).	80 weeks
Secondary	rPFS assessed by BICR	To evaluate the impact of Senaparib on rPFS, compared with the placebo, in mCRPC patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy assessed by BICR.	80 weeks
Secondary	Time to pain progression	To evaluate the impact of Senaparib on time to pain progression, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy.	80 weeks
Secondary	Time from randomization to the first SSRE	To evaluate the impact of Senaparib on time to the first symptomatic skeletal related events (SSRE), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy.	80 weeks
Secondary	OS	To evaluate the impact of Senaparib on overall survival (OS), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration who have not progressed after docetaxel therapy.	80 weeks
Secondary	PFS2	To evaluate the impact of Senaparib on second progression (PFS2), compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	Time to pain progression	To evaluate the impact of Senaparib on time to pain progression, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	Time from randomization to the first SSRE	To evaluate the impact of Senaparib on time to the first SSRE, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	OS	To evaluate the impact of Senaparib on OS, compared with the placebo, in mCRPC patients with HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	rPFS assessed by the investigator	To evaluate the impact of Senaparib on rPFS assessed by the investigator, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	Time to PSA progression	To evaluate the impact of Senaparib on time to prostate-specific antigen (PSA) progression, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	Objective response rate (ORR) according to RECIST v1.1 assessed by BICR	To evaluate the impact of Senaparib on radiographic response rate assessed by BICR, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have measurable lesion and have not progressed after docetaxel therapy.	80 weeks
Secondary	Objective response rate (ORR) according to RECIST v1.1 assessed by investigator	To evaluate the impact of Senaparib on radiographic response rate assessed by the investigator, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have measurable lesion and have not progressed after docetaxel therapy.	80 weeks
Secondary	PSA response rate according to PCWG3 criteria assessed by central laboratory	To evaluate the impact of Senaparib on PSA response rate, compared with the placebo, in mCRPC patients with BRCA1/2 gene alteration and HRR gene alterations who have not progressed after docetaxel therapy.	80 weeks
Secondary	Safety endpoints	Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.	80 weeks
Secondary	Cmax	Maximum plasma concentration,To characterize the plasma PK profile of Senaparib via population PK (popPK) modeling	80 weeks