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

December 14, 2021 updated by: Impact Therapeutics, Inc.

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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Anticipated)

285

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Senaparib (IMP4297) 20 mg
During the treatment period, eligible patients will receive single agent of Senaparib at a dose of 100 mg once daily (QD), continuously on a 4-week cycle
Drug: Placebo
Senaparib-matched placebo capsules
PLACEBO_COMPARATOR: Placebo
During the treatment period, eligible patients will receive placebo QD, continuously on a 4-week cycle
Drug: Senaparib
20 mg capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rPFS assessed by BICR
Time Frame: 80 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
rPFS assessed by BICR
Time Frame: 80 weeks
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
Time to pain progression
Time Frame: 80 weeks
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
Time from randomization to the first SSRE
Time Frame: 80 weeks
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
OS
Time Frame: 80 weeks
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
PFS2
Time Frame: 80 weeks
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
Time to pain progression
Time Frame: 80 weeks
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
Time from randomization to the first SSRE
Time Frame: 80 weeks
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
OS
Time Frame: 80 weeks
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
rPFS assessed by the investigator
Time Frame: 80 weeks
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
Time to PSA progression
Time Frame: 80 weeks
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
Objective response rate (ORR) according to RECIST v1.1 assessed by BICR
Time Frame: 80 weeks
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
Objective response rate (ORR) according to RECIST v1.1 assessed by investigator
Time Frame: 80 weeks
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
PSA response rate according to PCWG3 criteria assessed by central laboratory
Time Frame: 80 weeks
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
Safety endpoints
Time Frame: 80 weeks
Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.
80 weeks
Cmax
Time Frame: 80 weeks
Maximum plasma concentration，To characterize the plasma PK profile of Senaparib via population PK (popPK) modeling
80 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Impact Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

December 31, 2021

Primary Completion (ANTICIPATED)

May 1, 2024

Study Completion (ANTICIPATED)

August 1, 2024

Study Registration Dates

First Submitted

September 3, 2020

First Submitted That Met QC Criteria

March 26, 2021

First Posted (ACTUAL)

March 30, 2021

Study Record Updates

Last Update Posted (ACTUAL)

December 16, 2021

Last Update Submitted That Met QC Criteria

December 14, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • IMP4297-202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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