Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma
Phase Ib Study of Fluzoparib in Combination With Camrelizumab and Temozolomide in Advanced Melanoma With Homologous Recombination (HR) Mutation ，a Single-center Open-label Exploratory Clinical Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. Non-BRCA deficiencies in homologous recombination DNA repair genes could also enhance tumor cell sensitivity to PARP inhibitors. Therefore, PARP inhibitors are also selectively cytotoxic for cancer cells with deficiencies in DNA repair proteins other than BRCA1 and BRCA2.
In melanoma, genetic HR mutation/ alterations are rather common. Retrospective data showed that nearly18-40% of melanoma harbors a mutation in at least 1 of the HR genes in their tumor. The commonly altered genes were ARID1A, FANCA, ATM, BRCA1, ATRX and BRCA2, ATR, BRCA1 BRIP1 and SF3B1. These findings indicate that HR mutations / alterations are frequently observed in metastatic melanoma, and they suggest that PARP inhibitors could potentially be of a great clinical value in a substantial portion of the patients with advanced melanoma.
In this clinical study, clinical efficacy of fluzoparib in combination with camrelizumab and temozolomide will be evaluated by assessing an objective clinical response rate in patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jun Guo
- Phone Number: 86-10-88121122
- Email: guoj307@126.com
Study Contact Backup
- Name: Bin Lian
- Phone Number: 86-10-88121122
- Email: lianbin0214@126.com
Study Locations
-
-
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Beijing, China
- Recruiting
- Beijing Cancer Hospital
-
Contact:
- Jun Guo
- Email: guoj307@126.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma;
- Must have genetic HR and/or SF3B1 mutation/ alteration;
- Must have measurable disease based on RECIST 1.1;
- Must have an ECOG performance status of 0 to 1;
- Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline;
- Anticipated overall survival more than 3 months;
- Male and no pregnant female, able to adapt birth control methods during treatment.
Exclusion Criteria:
- Previously treated with a PARP inhibitor;
- Hypersensitivity to Fluzoparib or Camrelizumab or Temozolomide;
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
- Patients with a history of other (including unknown primary) malignancies within 5 years prior to the first dose of trial treatment;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Camre+Fluzo+TMZ
This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration .
|
Fluzoparib 50-150mg bid po, d1-21, q3w Camrelizumab 200mg iv, d1, q3w Temozolomide 50mg/m2-200mg/m2 d1-5,q3w
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Objective Response Rate (ORR)
Time Frame: 6 months
|
ORR of Fluzoparib in combination with Camrelizumab and Temozolomide in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Jun Guo, Peking University Cancer Hospital & Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Site
- Neoplasms
- Neoplasms by Histologic Type
- Skin Diseases
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Skin Neoplasms
- Melanoma
- Poly(ADP-ribose) Polymerase Inhibitors
- Antineoplastic Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Temozolomide
- Fluzoparib
Other Study ID Numbers
- MA-MM-Ⅱ-005
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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