The Combination of Radiotherapy，Surufatinib and Sintilimab in High-Risk Localized Soft Tissue Sarcoma

NCT ID: NCT05839275

Last Updated: 2023-08-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2029-07-31

Brief Summary

This is a prospective, single-center, single-arm, phase Ib/II clinical trial. The study aims to evaluate the safety and efficacy of the treatment which combines radiotherapy, Sintilimab (Anti-PD1 Antibody) and Surufatinib (small-molecule Tyrosine Kinase inhibitor) in patients with high-risk localized soft tissue sarcoma.

There will be 52 patients with high-risk localized extremity and trunck soft tissue sarcoma recruited. The trail is designed as a two-stage study. In safety lead-in phase (phase Ib), using 3+3 design, 6 cycles of Surufatinib (250mg, 200mg, qd) and Sintilimab (200mg, q3w) will be applied. And radiotherapy (BED=50-60Gy (α/β=10)) will begin in week 4 of the therapy. In extended phase (phase II), Surufatinib will be applied in the recommended phase 2 dose (RP2D) according to phase Ib. And 200mg Sintilimab and radiotherapy will be applied as before. The dose-limiting toxicity (DLT) in phase Ib and objective response rate (ORR) in phase Ib+Phase II will be mainly analyzed.

Conditions

High-Risk Localized Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

There will be 52 patients with high-risk localized extremity and truncal soft tissue sarcoma recruited.

In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 6 cycles of Surufatinib in three different dosages and Sintilimab. And radiotherapy will begin in week 4.

In extended phase (phase II): Surufatinib in RP2D, Sintilimab and radiotherapy will be applied as before.

Group Type: EXPERIMENTAL

Surufatinib

Intervention Type: DRUG

In phase Ib: 250mg, 200mg, d1-21，qd; In phase II: recommended phase 2 dose (RP2D), d1-21，qd.

Sintilimab

Intervention Type: DRUG

200mg, d1, q3w

Radiotherapy

Intervention Type: RADIATION

BED=50-60Gy (α/β=10); Radiation dose depends on tumor characteristics and organs at risk.

Starts at the begin of the second cycle of systemic therapy (week 4 of the therapy).

Interventions

Surufatinib

In phase Ib: 250mg, 200mg, d1-21，qd; In phase II: recommended phase 2 dose (RP2D), d1-21，qd.

Intervention Type: DRUG

Sintilimab

200mg, d1, q3w

Intervention Type: DRUG

Radiotherapy

BED=50-60Gy (α/β=10); Radiation dose depends on tumor characteristics and organs at risk.

Starts at the begin of the second cycle of systemic therapy (week 4 of the therapy).

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Aged from 18 to 70, with life expectancy more than 2 years
• Histologically confirmed STS, G2 or G3
• Has imaging-confirmed localized lesions on the limbs or trunk without distant metastases
• Has>5 cm lesions, or the lesions are determined to be borderline resectable or unresectable by a multidisciplinary consultation.
• Experience local recurrence after surgery (disease-free survival more than 2 months after surgery) or primary tumor
• ECOG performance status 0-1
• Demonstrate adequate organ function (bone marrow, liver, kidney and clotting function) within 7 days before the first administration without using blood products or hematopoietic stimulating factors.
• Fully informed and willing to provide written informed consent for the trial

Exclusion Criteria

• The presence of regional or distant metastases detected by imaging evaluation
• The following histological types: osteosarcoma, chordoma, classic chondrosarcoma, Kaposi's sarcoma, malignant mesothelioma, radiation-induced sarcomas
• History of another primary malignant tumor within the past three years or at the same time (excluding localized basal cell carcinoma, cutaneous squamous cell carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, adenocarcinoma in situ of cervix, or other previous malignant tumor with a disease-free survival of more than 10 years)
• Receiving any other chemotherapy or targeted therapy within 4 weeks before enrollment
• Prior treatment using anti-PD1 immunotherapy
• Prior radiotherapy towards the target lesion or has other contraindications to radiotherapy or surgery
• Baseline laboratory indicators do not meet the following criteria: neutrophils

≥1.5×10^9/L, Hb≥90g/L, PLT≥100×10^9/L , ALT ≤2.5 ULN, AST ≤2.5 ULN, Cr≤ 1.5 ULN or creatinine clearance rate <50ml/min, TBIL ≤1.5 ULN, APTT≤1.5 ULN, PT ≤1.5 ULN

• Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h
• Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg
• Uncontrolled hyperglycemia or coagulation disorder
• Active infection requiring systemic anti-infective therapy
• Uncontrolled mental diseases
• Previous surgery within 2 weeks of before enrollment (excluding diagnostic biopsy or peripherally inserted central catheter implantation)
• History of immunodeficiency diseases or active autoimmune disease requiring systemic treatment
• Pregnant or lactating women
• Allergic to any component of the therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhen Zhang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhen Zhang, M.D, PH.D

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yan Wang, M.D, PH.D

Role: CONTACT

wangxyyan@sina.com

18121299388

Facility Contacts

Zhen Zhang, M.D, PH.D

Role: primary

zhen_zhang@fudan.edu.cn

19521280960

Other Identifiers

FDRT-2021-328-2631-A1

Identifier Type: -

Identifier Source: org_study_id