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

NCT05839275 | Recruiting Phase 1

• 1 other identifier: FDRT-2021-328-2631-A1
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The percentage of patients with objective response. Objective response is defined as complete response (CR) or partial response (PR) per response evaluation criteria (RECIST v1.1) before surgery.

  The objective response rate (ORR) will be evaluated before surgery.

Secondary Outcomes (10)

• Pathological Complete Response (pCR) and Near pCR Rate

  The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.

• Non-Perfused Volume (NPV)

  The non-perfused volume (NPV) will be measured in four weeks before preoperative treatment and before surgery in week18-21.

• Adverse Events

  From the beginning of treatment to 90 days after the end of the last treatment.

• Wound Complications

  Up to 120 days from the surgery.

• Local Control Rate

  From the start of treatment to local recurrence, up to 5 years.

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: Surufatinib; Drug: Sintilimab; Radiation: Radiotherapy

Interventions

Surufatinib DRUG

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

Treatment Arm

Sintilimab DRUG

200mg, d1, q3w

Treatment Arm

Radiotherapy 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).

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

surufatinib; sintilimab; Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Zhen Zhang, M.D, PH.D

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Wang, M.D, PH.D

CONTACT

18121299388; wangxyyan@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 10, 2023
• First Posted: May 3, 2023
• Study Start: August 1, 2022
• Primary Completion: July 31, 2024
• Study Completion (Estimated): July 31, 2029
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

CN (1)