Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer

December 3, 2024 updated by: Xing Xie

Fuzuloparib Plus Arsenic Trioxide in Patients With Platinum Resistance Relapsed Ovarian Cancer

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2
  • Phase 1

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

  • China
    • Hangzhou
      • Zhejiang, Hangzhou, China, 310006
        • Recruiting
        • Women's Hospital School of Medicine Zhejiang University
        • Contact:
        • Contact:

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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

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: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: study group
Fuzuloparib Capsules plus table Arsenic Trioxide po
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: From date of randomization until PD or death from any cause, assessed up to 36 months.
ORR is defined as the rate of CR or PR, as determined by IRC using RECIST v1.1 criteria among patients with at least one target lesion. Activity was also described in women with nontarget lesions only and in women without any tumor lesion but with elevated CA-125 levels before starting treatment.
From date of randomization until PD or death from any cause, assessed up to 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: From date of randomization until the date of death from any cause, or date of last follow-up for patients still alive, assessed up to 36 months]
overall survival
From date of randomization until the date of death from any cause, or date of last follow-up for patients still alive, assessed up to 36 months]
PFS
Time Frame: From date of randomization until the date of first documented progression or death from any cause, whichever occurred first, or last follow-up for patients alive without progression, assessed up to approximately 36 months
PFS is defined as the time from randomization to the first occurrence of PD, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first.
From date of randomization until the date of first documented progression or death from any cause, whichever occurred first, or last follow-up for patients alive without progression, assessed up to approximately 36 months
the incidence and severity of adverse reactions
Time Frame: A summary of adverse events of each cycle,from date of administration of drugs until 30 days after the last chemotherapy or progression,whichever came first,assessed up to 36 months
Evaluate the adverse reactions rate of drugs assessed by number and severity of adverse events in the treatment.
A summary of adverse events of each cycle,from date of administration of drugs until 30 days after the last chemotherapy or progression,whichever came first,assessed up to 36 months
quality of life assessment
Time Frame: It will be assessed at baseline and before the administration of drugs at each first day of every two chemotherapy cycles, up to 6 cycles,each cycle is 28days.
according to the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30).The basic content of life quality assessment includes: physical health, mental health, social function, disease status and overall health perception.
It will be assessed at baseline and before the administration of drugs at each first day of every two chemotherapy cycles, up to 6 cycles,each cycle is 28days.

Collaborators and Investigators

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

Sponsor

Xing Xie

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 (Actual)

July 1, 2020

Primary Completion (Estimated)

December 3, 2024

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

August 16, 2020

First Submitted That Met QC Criteria

August 16, 2020

First Posted (Actual)

August 19, 2020

Study Record Updates

Last Update Posted (Actual)

December 4, 2024

Last Update Submitted That Met QC Criteria

December 3, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CESM023

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on Efficacy and Safety

Clinical Trials on Arsenic trioxide Tablet +Fuzuloparib Capsules

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe