Back to resultsFuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer
Primary Purpose
Efficacy and Safety
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Arsenic trioxide Tablet +Fuzuloparib Capsules
Sponsored by
About this trial
This is an interventional treatment trial for Efficacy and Safety focused on measuring PARPI, Arsenic Trioxide, High Grade Serous Carcinoma, High Grade Endometria Carcinoma, Platinum-resistant Ovarian Cancer, Fuzuloparib
Eligibility 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.
Sites / Locations
- Women's Hospital School Of Medicine Zhejiang UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
study group
Arm Description
Fuzuloparib Capsules plus table Arsenic Trioxide po
Outcomes
Primary Outcome Measures
ORR
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
OS
overall survival
PFS
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.
the incidence and severity of adverse reactions
Evaluate the adverse reactions rate of drugs assessed by number and severity of adverse events in the treatment.
quality of life assessment
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04518501
Brief Title
Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer
Official Title
Fuzuloparib Plus Arsenic Trioxide in Patients With Platinum Resistance Relapsed Ovarian Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Xing Xie
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Efficacy and Safety
Keywords
PARPI, Arsenic Trioxide, High Grade Serous Carcinoma, High Grade Endometria Carcinoma, Platinum-resistant Ovarian Cancer, Fuzuloparib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
study group
Arm Type
Experimental
Arm Description
Fuzuloparib Capsules plus table Arsenic Trioxide po
Intervention Type
Drug
Intervention Name(s)
Arsenic trioxide Tablet +Fuzuloparib Capsules
Intervention Description
Arsenic trioxide Tablet : 0.27*9 tid po consecutive 21 days with 1 week rest． Fuzuloparib Capsules: 150 mg bid po
Primary Outcome Measure Information:
Title
ORR
Description
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.
Time Frame
From date of randomization until PD or death from any cause, assessed up to 36 months.
Secondary Outcome Measure Information:
Title
OS
Description
overall survival
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]
Title
PFS
Description
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.
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
Title
the incidence and severity of adverse reactions
Description
Evaluate the adverse reactions rate of drugs assessed by number and severity of adverse events in the treatment.
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
Title
quality of life assessment
Description
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.
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.
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
yuanming shen, PhD
Phone
13588193832
Email
13588193832@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
xing xie, PhD
Phone
13606705128
Email
xiex@zju.edu.cn
Facility Information:
Facility Name
Women's Hospital School Of Medicine Zhejiang University
City
Zhejiang
State/Province
Hangzhou
ZIP/Postal Code
310006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xing Xie, PhD
Phone
13606705128
Email
xiex@zju.edu.cn
First Name & Middle Initial & Last Name & Degree
Yuanming Shen, PhD
Phone
13588193832
Email
13588193832@163.com
12. IPD Sharing Statement
Learn more about this trial
Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer
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