Homologous Recombination Deficiency Alterations Metastatic Colorectal Cancer
Conditions
Keywords
Fluzoparib Plus Irinotecan, Homologous Recombination Deficiency (HRD) Alterations
Brief summary
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
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.
Interventions
DRUGFluzoparib
150mg,orally, bid (days 1-7) every 2 weeks
DRUGIrinotecan
30-90min continuous infusion 180mg/m2 Irinotecan on day 1, q2w
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate of Metastatic Colorectal Cancer,inculdthe proportion of patients with complete response or partial response | assessed up to 1 year | using RECIST v 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | assessed up to 1 year | Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator |
| Overall survival of Metastatic Colorectal Cancer, include time from randomization to death from any cause | assessed up to 2 year | Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator |
| The Safety of Fluzoparib Plus Irinotecan as Second-line Treatment in Patients With Homologous Recombination Deficiency (HRD) Metastatic Colorectal Cancer. | assessed up to 2 year | 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 |
Countries
China
Contacts
Primary ContactYe Xu, PhD
Outcome results
None listed