Efficacy and SafetyPhase 1/2NCT04518501
Fuzuloparib Arsenic Trioxide Platinum Resistance Relapsed Ovarian Cancer
A Phase 1/2 study testing Arsenic trioxide Tablet +Fuzuloparib Capsules in people with Efficacy and Safety, run by Xing Xie at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Efficacy and Safety
- What is being tested?
- Arsenic trioxide Tablet +Fuzuloparib Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2020to 1 Jan 2025
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 13Show fewer
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Women's Hospital School Of Medicine Zhejiang University
Zhejiang, Hangzhou, 310006
Xing Xie, PhD, 13606705128, xiex@zju.edu.cn
Yuanming Shen, PhD, 13588193832, 13588193832@163.com
About this study
Official title: 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.
Read the 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
- Being tested
- Arsenic trioxide Tablet +Fuzuloparib Capsules
- Keywords
- PARPI, Arsenic Trioxide, High Grade Serous Carcinoma, High Grade Endometria Carcinoma, Platinum-resistant Ovarian Cancer, Fuzuloparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic trioxide Tablet +Fuzuloparib CapsulesDrug
Arsenic trioxide Tablet : 0.27*9 tid po consecutive 21 days with 1 week rest． Fuzuloparib Capsules: 150 mg bid po
| Study group | Role | What they receive |
|---|---|---|
| study group | Experimental | Fuzuloparib Capsules plus table Arsenic Trioxide po Receives: Drug: Arsenic trioxide Tablet +Fuzuloparib Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of randomization until PD or death from any cause, assessed up to 36 months.
Secondary outcomes (4)
OS
overall survival
Measured: 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
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.
Measured: 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
Evaluate the adverse reactions rate of drugs assessed by number and severity of adverse events in the treatment.
Measured: 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
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2020
- Study start1 Jul 2020
- Primary completion3 Dec 2024 (estimated)
- Study completion1 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Efficacy and SafetyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xing Xie
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xing Xie, Women's Hospital School Of Medicine Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04518501
- Sponsor's protocol ID
- CESM023
- Status last verified
- Dec 2024
- First submitted
- 16 Aug 2020
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fuzuloparib Plus Arsenic Trioxide in Patients With Platinum Resistance Relapsed Ovarian Cancer
- ClinicalTrials.gov ID
- NCT04518501
- Acronym / sponsor ID
- CESM023
- Conditions
- Efficacy and Safety
- Keywords
- PARPI, Arsenic Trioxide, High Grade Serous Carcinoma, High Grade Endometria Carcinoma, Platinum-resistant Ovarian Cancer, Fuzuloparib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Xing XieUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 3 Dec 2024 (estimated)
- Study completion
- 1 Jan 2025 (estimated)
- First posted
- 19 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study group | Experimental | Drug: Arsenic trioxide Tablet +Fuzuloparib CapsulesFuzuloparib Capsules plus table Arsenic Trioxide po |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arsenic trioxide Tablet +Fuzuloparib CapsulesArsenic trioxide Tablet : 0.27*9 tid po consecutive 21 days with 1 week rest． Fuzuloparib Capsules: 150 mg bid po | Drug | study group |
Primary outcome
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.
4 secondary outcomes
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]
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
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
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Arsenic trioxide Tablet +Fuzuloparib Capsules in people with Efficacy and Safety, run by Xing Xie at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact yuanming shen, PhD (13588193832, 13588193832@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: From date of randomization until PD or death from any cause, assessed up to 36 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.