Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT04518501
• Recruitment Status: Recruiting
• First Posted: August 19, 2020
• Last Update Posted: January 25, 2022
• Sponsor: Xing Xie
• Information provided by (Responsible Party): Xing Xie, Women's Hospital School Of Medicine Zhejiang University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Efficacy and Safety	Drug: Arsenic trioxide Tablet +Fuzuloparib Capsules	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fuzuloparib Plus Arsenic Trioxide in Patients With Platinum Resistance Relapsed Ovarian Cancer
• Actual Study Start Date: July 1, 2020
• Estimated Primary Completion Date: January 1, 2024
• Estimated Study Completion Date: January 1, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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
2. 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.
3. 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.
4. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 18-70years old;
• High grade (serous or endometrioid) epithelial ovarian cancers, fallopian tube or primary peritoneal carcinoma;
• Recurrent disease within 6 months of the last receipt of platinum-based chemotherapy;
• Measurable disease as per RECIST 1.1
• ECOG 0-2;
• Life expectancy ≥12 weeks;
• Confirmation of BRCA1/2 mutation and homologous recombination 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:

• 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.

Contacts and Locations

Contacts

Contact: yuanming shen, PhD; 13588193832; 13588193832@163.com

Contact: xing xie, PhD; 13606705128; xiex@zju.edu.cn

Locations

China, Hangzhou

Women's Hospital School Of Medicine Zhejiang University; Recruiting

Zhejiang, Hangzhou, China, 310006

Contact: Xing Xie, PhD 13606705128 xiex@zju.edu.cn

Contact: Yuanming Shen, PhD 13588193832 13588193832@163.com

Sponsors and Collaborators

Xing Xie

More Information

• Responsible Party: Xing Xie, profressor, Women's Hospital School Of Medicine Zhejiang University
• ClinicalTrials.gov Identifier: NCT04518501
• Other Study ID Numbers: CESM023
• First Posted: August 19, 2020
• Last Update Posted: January 25, 2022
• Last Verified: January 2022

• 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

Keywords provided by Xing Xie, Women's Hospital School Of Medicine Zhejiang University:

PARPI; Arsenic Trioxide; High Grade Serous Carcinoma; High Grade Endometria Carcinoma; Platinum-resistant Ovarian Cancer; Fuzuloparib

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Arsenic Trioxide; Antineoplastic Agents