Clinical trial NCT05894018: Brachytherapy (Iodine-125 Seeds) and Fluzoparib Combination Therapy for Advanced Unresectable Soft Tissue Sarcoma
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sarcoma,Soft Tissue
Brachytherapy
Poly(ADP-ribose) Polymerase Inhibitors
Keywords: Fluzoparib
Radioactive particles
Iodine-125 seed
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-06-08
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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 Patients with intolerable toxicity or patient requested discontinuation or disease progression (PD) were withdrawn from the trial and entered into survival follow-up.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily agree to participate in this study and sign an informed consent form;
2. Age ≥18 (calculated on the day of signing the informed consent), regardless of gender;
3. 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);
4. A single lesion ≤5cm and no more than 5 lesions;
5. Received systemic therapy (such as standard treatment: doxorubicin plus ifosfamide) ± surgical resection as the first-line treatment;
6. Able to swallow pills normally;
7. ECOG performance status of 0-1;
8. Expected survival period ≥12 weeks;
9. 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:

1. 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);
2. 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;
3. 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 ;
4. 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;
5. Known hereditary or acquired bleeding and thrombotic predisposition (e.g., hemophiliacs, coagulation disorders, thrombocytopenia, etc.);
6. 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;
7. 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;
8. Patients with other malignancies (except cured basal cell carcinoma of the skin and cervical carcinoma in situ) within the previous 3 years or concurrently;
9. Patients with established bone metastases who have received, within 4 weeks prior to enrollment in the study;
10. Prior external radiotherapy to the lesion;
11. Pregnant or breastfeeding women, or women of childbearing age who do not wish to use contraception;
12. 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Progression-free survival rate(PFS)
timeFrame: 6 months
measure: Progression-free survival rate(PFS)
timeFrame: 12 months
measure: Progression-free survival rate(PFS)
timeFrame: 18 months
measure: Disease control rate(DCR)
timeFrame: 12 months
measure: Overall survival(OS)
timeFrame: 12 months
measure: Overall survival rate
timeFrame: 6 months
measure: Overall survival rate
timeFrame: 12 months
measure: Overall survival rate
timeFrame: 18 months
measure: AE, SAE
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Fujun Zhang, Ph.D,M.D
role: STUDY_DIRECTOR
affiliation: Sun Yat-sen University
name: Xing Zhang, Ph.D,M.D
role: STUDY_DIRECTOR
References: