Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer

NCT ID: NCT04518501

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2025-01-01

Brief Summary

Ovarian cancer is the leading cause of death from gynecologic tumors in the western world. Most patients have relapses, and responses to subsequent therapies are generally short-lived. Currently, the population that can benefit from PARPi is mainly focusing on BRCAm, then homologous-recombination deficiency patients. Limited data revealed the ORR was only 3-4% in homologous recombination proficiency patients with PARPi therapy. New treatments are urgently needed to improve patient outcomes.

To explore the efficacy and safety of Fuzuloparib in combination with Arsenic trioxide therapy in platinum-resistance relapsed Ovarian cancer patients.

Detailed Description

Ovarian cancer is the leading cause of death from gynecologic tumors in the western world. Most patients have relapses, and responses to subsequent therapies are generally short-lived. Currently, the population that can benefit from PARPi is mainly focusing on BRCAm, then homologous-recombination deficiency patients. Limited data revealed the ORR was only 3-4% in homologous recombination proficiency patients with PARPi therapy. New treatments are urgently needed to improve patient outcomes.

The investigators' studies have shown that combination therapy with Fuzuloparib and Arsenic trioxide demonstrated a synergistic anti-tumor effect in BRCAness/HR-proficiency ovarian cancer cells:

Firstly, CCK8 and clone formation assays showed that the combination of Fuzuloparib and Arsenic trioxide produced notable tumor cell growth inhibition than either single agent in SKOV3 and CAOV3 cells.

Further, the combination therapy resulted in significantly increased level of γ-H2AX and decreased level of RAD51 by IF.The investigators also found that combination therapy could remarkably induced cell apoptosis, which is associated with induction of cleave-PARP and reduction of p-AKT, when compared with either single drug. (Data not published) Therefore, the investigators hypothesis is that for those platinum-resistance relapsed patients who have received at least twice platinum-based chemotherapy, patients with combinate therapy will get 25% of ORR. And platinum-resistance in combination with Arsenic trioxide therapy is well tolerated.

Conditions

Efficacy and Safety

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study group

Fuzuloparib Capsules plus table Arsenic Trioxide po

Group Type: EXPERIMENTAL

Arsenic trioxide Tablet +Fuzuloparib Capsules

Intervention Type: DRUG

Arsenic trioxide Tablet : 0.27\*9 tid po consecutive 21 days with 1 week rest． Fuzuloparib Capsules: 150 mg bid po

Interventions

Arsenic trioxide Tablet +Fuzuloparib Capsules

Arsenic trioxide Tablet : 0.27\*9 tid po consecutive 21 days with 1 week rest． Fuzuloparib Capsules: 150 mg bid po

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18-70years old;
• High grade (serous or endometrioid) epithelial ovarian cancers, fallopian tube or primary peritoneal carcinoma;
• Patients received at least two lines of platinum-containing chemotherapy, with recurrence occurring within six months after the last chemotherapy dose, or were platinum-refractory patients who have undergone at least two cycles of platinum-based chemotherapy;
• Measurable disease as per RECIST 1.1
• ECOG 0-2;
• Life expectancy ≥12 weeks;
• Confirmation of BRCA1/2 mutation status;
• PARPi naive;
• LVEF ≥ 50%;
• Bone Marrow Function: ANC：≥1.5×109/L； PLT：≥100×109/L；Hb: ≥90g/L;
• Liver and renal function:Serum creatinine ≤ normal upper limit (ULN) 1.5times; aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤ULN 2.5times, or <ULN 5times in the presence of liver metastasis; total bilirubin (TBil) level≤ ULN 1.5 times, or ≤ ULN 2.5times if Gilbert's syndrome are present;
• The childbearing age subjects must agree to take effective contraceptive measures during the trial; the serum or urine pregnancy test must be negative, non-lactating;
• Signed the informed consent;

Exclusion Criteria

• Prior treatment with PARP inhibitors except under specific conditions: 1. Patients who previously received PARP inhibitor (PARPi) therapy without disease progression during treatment, but discontinued due to reasons such as treatment cost or adherence issues; 2. Patients who received only one prior PARPi therapy (excluding fuzuloparib), with maintenance therapy lasting ≥ 12 months. In both cases, the time since the last PARPi treatment must be >6 months prior to study enrollment;
• Patients who had previously received >20% bone marrow radiotherapy in 1 week;
• Other malignant tumors have been found in the past 5 years,except for cured cervical carcinoma in situ, non melanoma of the skin;
• Uncontrolled systemic infection requiring anti-infective treatment;
• Allergies to the Fuzuloparib or Arsenic Trioxide or their excipients or intolerant patients;
• Subjects with ≥2 grade peripheral neuropathy according to CTCAE V 4.03;
• Researchers think it is not suitable for enrolling.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Xing Xie

OTHER

Sponsor Role: lead

Responsible Party

Xing Xie

profressor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Women's Hospital School Of Medicine Zhejiang University

Zhejiang, Hangzhou, China

Site Status: RECRUITING

Countries

China

Central Contacts

yuanming shen, PhD

Role: CONTACT

13588193832@163.com

13588193832

xing xie, PhD

Role: CONTACT

xiex@zju.edu.cn

13606705128

Facility Contacts

Xing Xie, PhD

Role: primary

xiex@zju.edu.cn

13606705128

Yuanming Shen, PhD

Role: backup

13588193832@163.com

13588193832

Other Identifiers

CESM023

Identifier Type: -

Identifier Source: org_study_id