The Efficacy and Safety of Fluzoparib Plus Irinotecan as Second-line Treatment in Patients With Homologous Recombination Deficiency (HRD) Metastatic Colorectal Cancer.

Study Overview
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Brief Summary
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Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. However，in colorectal cancer (CRC), the role of HRD alterations is mostly unknown. This study aims to explore the the Efficacy and Safety of Fluzoparib combined with Irinotecan in the Second-line treatment of HRD alterations metastatic colorectal cancer.

Detailed Description
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Study protocol for an open-label, single-arm, phase II study of combination of Fluzoparib and rinotecan as the second-line treatment for patients with HRD alterations metastatic colorectal cancer (mCRC). Patients will receive Fluzoparib combined with Irinotecan treatment protocol, which included irinotecan asintravenous infusion at 180mg/m2 (on day 1) and Fluzoparib 150mg capsules given bid (days 1-7) every 2 weeks.

Official Title
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The Efficacy and Safety of Fluzoparib Combined With Fluzoparib as Second-line Treatment in Patients With Homologous Recombination Deficiency (HRD) Metastatic Colorectal Cancer: A Single-center, Open-label, Single-arm Study .

Conditions
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Homologous Recombination Deficiency Alterations Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Fluzoparib
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-75 years； Histological or cytological confirmed metastatic colorectal cancer; HRD alterations（inclued BRCA1/2、ATM、CDK12、PALB2、Check2、RAD51C、RAD51D etc.）； Intolerability toxicity occurs 8 weeks within first-line therapy; ECOG PS 0-1; Adequate hepatic, renal, heart, and hematologic functions; Negative serum pregnancy test at screening for women of childbearing potential; Informed consent was signed before the study began. Exclusion Criteria: Prior treatment with PARPi drugs； Symptomatic brain or meningeal metastases； Patients have received local radiotherapy within 1 month prior to treatment; Patients who had active bleeding or coagulopathy before enrollment, had a tendency to bleed, or were receiving thrombolytic therapy and were considered by the investigator to be ineligible for enrollment; Women who are pregnant (with a positive pregnancy test before medication) or breastfeeding; Expected survival <3 months; Received other investigational drugs within 4 weeks prior to treatment; Patients who had active uncontrollable neurological, mental disease or mental disorder, poor compliance, unable to cooperate and describe the treatment response; Allergy to the study drug or any of its excipients;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzoparib plus Irinotecan<br>Patients will receive Fluzoparib combined with Irinotecan treatment protocol, which included irinotecan asintravenous infusion at 180mg/m2 (on day 1) and Fluzoparib 150mg capsules given bid (days 1-7) every 2 weeks . | Drug: Fluzoparib<br>* 150mg,orally, bid (days 1-7) every 2 weeks<br>Drug: Irinotecan<br>* 30-90min continuous infusion 180mg/m2 Irinotecan on day 1, q2w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of Metastatic Colorectal Cancer,inculdthe proportion of patients with complete response or partial response | using RECIST v 1.1. | assessed up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival of Metastatic Colorectal Cancer，includ time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first | Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator | assessed up to 1 year | 
| Overall survival of Metastatic Colorectal Cancer, include time from randomization to death from any cause | Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator | assessed up to 2 year | 
| The Safety of Fluzoparib Plus Irinotecan as Second-line Treatment in Patients With Homologous Recombination Deficiency (HRD) Metastatic Colorectal Cancer. | time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator | assessed up to 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluzoparib Plus Irinotecan, Homologous Recombination Deficiency (HRD) Alterations