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Brachytherapy (Iodine-125 Seeds) and Fluzoparib Combination Therapy for Advanced Unresectable Soft Tissue Sarcoma (RAFAS-001)

Primary Purpose

Sarcoma,Soft Tissue, Brachytherapy, Poly(ADP-ribose) Polymerase Inhibitors

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Fluzoparib
Radioactive particle implantation
Sponsored by
Fujun Zhang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma,Soft Tissue focused on measuring Fluzoparib, Radioactive particles, Iodine-125 seed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Voluntarily agree to participate in this study and sign an informed consent form; Age ≥18 (calculated on the day of signing the informed consent), regardless of gender; Pathologically confirmed soft tissue sarcoma, with at least one measurable lesion according to RECIST 1.1 criteria on CT or MRI scan, within 28 days before the first study treatment (the longest diameter of the lesion ≥10 mm or the short diameter of swollen lymph node ≥15 mm); A single lesion ≤5cm and no more than 5 lesions; Received systemic therapy (such as standard treatment: doxorubicin plus ifosfamide) ± surgical resection as the first-line treatment; Able to swallow pills normally; ECOG performance status of 0-1; Expected survival period ≥12 weeks; Normal function of important organs, including: Absolute neutrophil count ≥1.5×109/L;Platelets ≥80×109/L;Hemoglobin ≥90 g/L;Serum albumin ≥28 g/L;Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously, and if FT3 and FT4 levels are normal, patients can be included);Bilirubin ≤1.5×ULN (within 7 days before the first treatment);ALT and AST ≤3×ULN (within 7 days before the first treatment);Alkaline phosphatase (AKP) ≤2.5×ULN;Serum creatinine ≤1.5×ULN; Non-surgically sterilized or fertile female patients need to use a medically recognized contraceptive measure (such as an intrauterine device, birth control pills, or condoms) during the study treatment period and within 3 months after the end of the study treatment. Fertile female patients who are not surgically sterilized must have a negative serum or urine HCG test within 72 hours before study enrollment and must not be breastfeeding. Male patients with fertile female partners should also use effective contraception during the trial period and for 3 months after the last dose of the study treatment. Exclusion Criteria: Clinical cardiac symptoms or disease that were not well controlled, such as: NYHA class 2 or higher heart failure, unstable angina, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, QTc>450ms (men); QTc>470ms (women); Coagulation abnormal function (INR>2.0, PT>16s), bleeding tendency or on thrombolytic or anticoagulant therapy, prophylactic use of low-dose aspirin, low-molecular heparin allowed; Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such as daily cough/hemoptysis of 2.5 ml or more, gastrointestinal bleeding, esophagogastric fundic varices with bleeding risk ; Arterial/venous thrombotic events such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, and cerebrovascular disease) that occurred within 6 months prior to enrollment. ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Known hereditary or acquired bleeding and thrombotic predisposition (e.g., hemophiliacs, coagulation disorders, thrombocytopenia, etc.); Patients who have received prior chemotherapy, surgery, less than 4 weeks after completion of treatment (last dose) and prior to study dosing; or patients who have not recovered from adverse events (other than alopecia) caused by prior treatment to ≤ CTCAE grade 1; Patients with active infection, unexplained fever ≥38.5°C within 7 days prior to dosing, or white blood cell count >15×109/L at baseline; Patients with other malignancies (except cured basal cell carcinoma of the skin and cervical carcinoma in situ) within the previous 3 years or concurrently; Patients with established bone metastases who have received, within 4 weeks prior to enrollment in the study; Prior external radiotherapy to the lesion; Pregnant or breastfeeding women, or women of childbearing age who do not wish to use contraception; Patients who, in the judgment of the investigator, have other factors that may affect the outcome of the study or force the termination of the study, such as alcoholism, substance abuse, other serious illnesses (including mental illness) requiring comorbid treatment, severe abnormal laboratory tests, accompanied by family or social factors that would affect the safety of the patient.

Sites / Locations

  • Sun Yat-sen University Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fluzoparib+radioactive particle implantation

Arm Description

Fluzoparib 150 mg bid was given orally after meals for 2 months (60 days) in a continuous cycle 48h after radioactive particle implantation.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of The proportion of patients achieving complete response (CR, tumor disappearance) or partial response (PR, tumor shrinkage) as evaluated by researchers based on the RECIST 1.1 criteria after receiving treatment.

Secondary Outcome Measures

Progression-free survival rate(PFS)
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 6 months after treatment was calculated using the Kaplan-Meier method.
Progression-free survival rate(PFS)
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 12 months after treatment was calculated using the Kaplan-Meier method.
Progression-free survival rate(PFS)
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 18 months after treatment was calculated using the Kaplan-Meier method.
Disease control rate(DCR)
Defined as the proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) for at least 4 weeks after treatment.
Overall survival(OS)
Defined as the time interval from the date of enrollment to death from any cause, with censoring at the last known alive date if no death has occurred.
Overall survival rate
Defined as the proportion of patients who are still alive at 6 months from the initiation of treatment during follow-up.
Overall survival rate
Defined as the proportion of patients who are still alive at 12 months from the initiation of treatment during follow-up.
Overall survival rate
Defined as the proportion of patients who are still alive at 18 months from the initiation
AE, SAE
The incidence of adverse events (AE), serious adverse events (SAE)

Full Information

First Posted
May 26, 2023
Last Updated
July 24, 2023
Sponsor
Fujun Zhang
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1. Study Identification

Unique Protocol Identification Number
NCT05894018
Brief Title
Brachytherapy (Iodine-125 Seeds) and Fluzoparib Combination Therapy for Advanced Unresectable Soft Tissue Sarcoma
Acronym
RAFAS-001
Official Title
A Phase II Clinical Trial Evaluating the Safety and Efficacy of Radioactive Particle and Fluzoparib Combination Therapy in the Treatment of Advanced Unresectable Soft Tissue Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 29, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Fujun Zhang

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To evaluate the effectiveness and safety of radioactive particles in combination with the PARP inhibitor fluzoparib in the treatment of advanced inoperable soft tissue sarcoma.
Detailed Description
Fluzoparib 150 mg Bid was given orally after meals for 2 months (60 days) in a continuous cycle 48 h after radioactive particle implantation. The maximum cumulative dosing period is 1 year. Tumor assessment was performed in each cycle. The first cycle is evaluated every month. Patients in partial remission (PR) or patients with stable disease (SD) will be supplemented with additional particle implantations (≤3) according to the dose prescribed by the physician, noting the need to discontinue the drug for at least 5 days prior to surgery and to continue oral Fluzoparib for 2 days after surgery until 6 months after the last particle implantation. Patients with intolerable toxicity or patient requested discontinuation or disease progression (PD) were withdrawn from the trial and entered into survival follow-up.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma,Soft Tissue, Brachytherapy, Poly(ADP-ribose) Polymerase Inhibitors
Keywords
Fluzoparib, Radioactive particles, Iodine-125 seed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Fluzoparib 150 mg Bid was given orally after meals for 2 months (60 days) in a continuous cycle 48 h after radioactive particle implantation. The maximum cumulative dosing period is 1 year. Tumor assessment was performed in each cycle. The first cycle is evaluated every month. Patients in partial remission (PR) or patients with stable disease (SD) will be supplemented with additional particle implantations (≤3) according to the dose prescribed by the physician, noting the need to discontinue the drug for at least 5 days prior to surgery and to continue oral Fluzoparib for 2 days after surgery until 6 months after the last particle implantation. Patients with intolerable toxicity or patient requested discontinuation or disease progression (PD) were withdrawn from the trial and entered into survival follow-up.
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fluzoparib+radioactive particle implantation
Arm Type
Experimental
Arm Description
Fluzoparib 150 mg bid was given orally after meals for 2 months (60 days) in a continuous cycle 48h after radioactive particle implantation.
Intervention Type
Drug
Intervention Name(s)
Fluzoparib
Intervention Description
150mg, orally, bid
Intervention Type
Procedure
Intervention Name(s)
Radioactive particle implantation
Intervention Description
Radioactive iodine-125 seeds implantation
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR was defined as the percentage of participants with a best overall response of The proportion of patients achieving complete response (CR, tumor disappearance) or partial response (PR, tumor shrinkage) as evaluated by researchers based on the RECIST 1.1 criteria after receiving treatment.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression-free survival rate(PFS)
Description
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 6 months after treatment was calculated using the Kaplan-Meier method.
Time Frame
6 months
Title
Progression-free survival rate(PFS)
Description
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 12 months after treatment was calculated using the Kaplan-Meier method.
Time Frame
12 months
Title
Progression-free survival rate(PFS)
Description
Based on RECIST 1.1 criteria, all patients were evaluated from the first day of iodine-125 seeds brachytherapy treatment until objective tumor progression or death from any cause. The percentage of subjects with progression-free survival at 18 months after treatment was calculated using the Kaplan-Meier method.
Time Frame
18 months
Title
Disease control rate(DCR)
Description
Defined as the proportion of subjects achieving complete response (CR), partial response (PR), or stable disease (SD) for at least 4 weeks after treatment.
Time Frame
12 months
Title
Overall survival(OS)
Description
Defined as the time interval from the date of enrollment to death from any cause, with censoring at the last known alive date if no death has occurred.
Time Frame
12 months
Title
Overall survival rate
Description
Defined as the proportion of patients who are still alive at 6 months from the initiation of treatment during follow-up.
Time Frame
6 months
Title
Overall survival rate
Description
Defined as the proportion of patients who are still alive at 12 months from the initiation of treatment during follow-up.
Time Frame
12 months
Title
Overall survival rate
Description
Defined as the proportion of patients who are still alive at 18 months from the initiation
Time Frame
18 months
Title
AE, SAE
Description
The incidence of adverse events (AE), serious adverse events (SAE)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Voluntarily agree to participate in this study and sign an informed consent form; Age ≥18 (calculated on the day of signing the informed consent), regardless of gender; Pathologically confirmed soft tissue sarcoma, with at least one measurable lesion according to RECIST 1.1 criteria on CT or MRI scan, within 28 days before the first study treatment (the longest diameter of the lesion ≥10 mm or the short diameter of swollen lymph node ≥15 mm); A single lesion ≤5cm and no more than 5 lesions; Received systemic therapy (such as standard treatment: doxorubicin plus ifosfamide) ± surgical resection as the first-line treatment; Able to swallow pills normally; ECOG performance status of 0-1; Expected survival period ≥12 weeks; Normal function of important organs, including: Absolute neutrophil count ≥1.5×109/L;Platelets ≥80×109/L;Hemoglobin ≥90 g/L;Serum albumin ≥28 g/L;Thyroid-stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4 levels should be examined simultaneously, and if FT3 and FT4 levels are normal, patients can be included);Bilirubin ≤1.5×ULN (within 7 days before the first treatment);ALT and AST ≤3×ULN (within 7 days before the first treatment);Alkaline phosphatase (AKP) ≤2.5×ULN;Serum creatinine ≤1.5×ULN; Non-surgically sterilized or fertile female patients need to use a medically recognized contraceptive measure (such as an intrauterine device, birth control pills, or condoms) during the study treatment period and within 3 months after the end of the study treatment. Fertile female patients who are not surgically sterilized must have a negative serum or urine HCG test within 72 hours before study enrollment and must not be breastfeeding. Male patients with fertile female partners should also use effective contraception during the trial period and for 3 months after the last dose of the study treatment. Exclusion Criteria: Clinical cardiac symptoms or disease that were not well controlled, such as: NYHA class 2 or higher heart failure, unstable angina, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, QTc>450ms (men); QTc>470ms (women); Coagulation abnormal function (INR>2.0, PT>16s), bleeding tendency or on thrombolytic or anticoagulant therapy, prophylactic use of low-dose aspirin, low-molecular heparin allowed; Clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment, such as daily cough/hemoptysis of 2.5 ml or more, gastrointestinal bleeding, esophagogastric fundic varices with bleeding risk ; Arterial/venous thrombotic events such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, and cerebrovascular disease) that occurred within 6 months prior to enrollment. ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; Known hereditary or acquired bleeding and thrombotic predisposition (e.g., hemophiliacs, coagulation disorders, thrombocytopenia, etc.); Patients who have received prior chemotherapy, surgery, less than 4 weeks after completion of treatment (last dose) and prior to study dosing; or patients who have not recovered from adverse events (other than alopecia) caused by prior treatment to ≤ CTCAE grade 1; Patients with active infection, unexplained fever ≥38.5°C within 7 days prior to dosing, or white blood cell count >15×109/L at baseline; Patients with other malignancies (except cured basal cell carcinoma of the skin and cervical carcinoma in situ) within the previous 3 years or concurrently; Patients with established bone metastases who have received, within 4 weeks prior to enrollment in the study; Prior external radiotherapy to the lesion; Pregnant or breastfeeding women, or women of childbearing age who do not wish to use contraception; Patients who, in the judgment of the investigator, have other factors that may affect the outcome of the study or force the termination of the study, such as alcoholism, substance abuse, other serious illnesses (including mental illness) requiring comorbid treatment, severe abnormal laboratory tests, accompanied by family or social factors that would affect the safety of the patient.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fujun Zhang, Ph.D,M.D
Phone
+8613826222266
Email
zhangfj@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Dengyao Liu, Ph.D
Phone
+8618599037139
Email
liudy1@sysucc.org.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fujun Zhang, Ph.D,M.D
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Xing Zhang, Ph.D,M.D
Organizational Affiliation
Sun Yat-sen University
Official's Role
Study Director
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Funjun Zhang, Ph.D,M.D
Phone
+8613826222266
Email
zhangfj@sysucc.org.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Brachytherapy (Iodine-125 Seeds) and Fluzoparib Combination Therapy for Advanced Unresectable Soft Tissue Sarcoma

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