The Combination of Radiotherapy, Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma

NCT ID: NCT05774275

Last Updated: 2023-03-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-25
• Study Completion Date: 2029-08-24

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, chemotherapy and immunotherapy in patients with high-risk localized soft tissue sarcoma.

There will be 52 patients with high-risk localized extremity and trunk soft tissue sarcoma recruited. The trail is designed as a two-stage study. In safety lead-in phase (phase Ib), using 3+3 design, 4 cycles of Doxil (37.5 mg/m2, 30 mg/m2, q3w) or doxorubicin hydrochloride (75mg/m2, q3w), Sintilimab (200mg, q3w) and radiotherapy (BED=50-60Gy (α/β=10)) will be applied. In phase II, Doxil 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 trunk soft tissue sarcoma recruited.

In safety lead-in phase (phase Ib): using 3+3 design, patients will receive 4 cycles of Doxil or doxorubicin hydrochloride, sintilimab and radiotherapy.

In phase II: Doxil in RP2D, sintilimab and radiotherapy will be applied as before.

Group Type: EXPERIMENTAL

Pegylated Liposomal Doxorubicin

Intervention Type: DRUG

In phase Ib: 37.5 mg/m2, 30 mg/m2, d1, q3w; In phase II: recommended phase 2 dose (RP2D), d1, q3w.

Doxorubicin

Intervention Type: DRUG

75mg/m2, d1, q3w Doxorubicin hydrochloride will be administered if subject is allergic to Doxil.

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

200 mg, d1, q3w

Radiotherapy

Intervention Type: RADIATION

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

Interventions

Pegylated Liposomal Doxorubicin

In phase Ib: 37.5 mg/m2, 30 mg/m2, d1, q3w; In phase II: recommended phase 2 dose (RP2D), d1, q3w.

Intervention Type: DRUG

Doxorubicin

75mg/m2, d1, q3w Doxorubicin hydrochloride will be administered if subject is allergic to Doxil.

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

200 mg, d1, q3w

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Other Intervention Names

Doxil; Doxorubicin Hydrochloride; Sintilimab

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed STS, G2 or G3. The histological types include: pleomorphic undifferentiated sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, myxofibrosarcoma, fibrosarcoma, angiosarcoma but not radiotherapy-induced angiosarcoma, etc.

2. Has>5 cm lesions, or the lesions are determined to be borderline resectable or unresectable by a multidisciplinary consultation.

3. Has imaging-confirmed localized lesions on the limbs or trunk without distant metastases.

4. Experience primary tumor or local recurrence after surgery (disease-free survival more than 2 months after surgery)

5. Aged from 18 to 70, with ECOG performance status 0-1, or aged from 70 to 75, with ECOG performance status 0. Has life expectancy more than 2 years

6. Demonstrate adequate organ function (bone marrow, liver, and kidney function) (Leukocytes ≥ 3 × 10^9 /L, Neutrophils ≥ 1.5 × 10^9 /L, Hemoglobin ≥ 90 g/L, Platelet count ≥ 100 × 10^9 /L, Total bilirubin ≤1.5 × institutional upper limit of normal (ULN), Aspartate transaminase ≤2.5 × ULN, Alanine transaminase ≤2.5 × ULN, Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min.)

7. Fully informed and willing to provide written informed consent for the trial.

Exclusion Criteria

1. The presences of regional or distant metastases detected by imaging evaluation

2. Patients with the following histological types: osteosarcoma, chordoma, classical chondrosarcoma, Kaposi's sarcoma, malignant mesothelioma, radiation-induced sarcomas.

3. Known 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 five years)

4. Known history of other chemotherapy within 4 weeks before enrolment, previous anti-PD1 treatment, previous radiotherapy in the radiation field, or has other contraindications to radiotherapy or surgery.

5. Uncontrolled hyperglycaemia or Coagulation disorder

6. Active infection requiring systemic anti-infective therapy

7. Previous major surgery within 2 weeks before enrolment (excluding minor operation such as diagnostic biopsy or peripherally inserted central catheter implantation)

8. Known history of immunodeficiency diseases or active autoimmune disease requiring systemic treatment

9. Female patients pregnant or breastfeeding, Male patients expecting to have babies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 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

Wangjun Yan, 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-2021-373-2676

Identifier Type: -

Identifier Source: org_study_id