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

NCT05774275 | Recruiting Phase 1

• 1 other identifier: FDRT-2021-373-2676
• 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, 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

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, which will be scheduled 5-12 weeks after the last fraction of radiotherapy.

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, which will be scheduled 5-12 weeks after the last fraction of radiotherapy.

• Acute Adverse Events

  through study completion, an average of 6 months.

• Wound Complications

  Up to 120 days from the surgery.

• Local Control Rate

  Up to 5 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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.

Drug: Pegylated Liposomal Doxorubicin; Drug: Doxorubicin; Drug: Anti-PD-1 monoclonal antibody; Radiation: Radiotherapy

Interventions

Pegylated Liposomal Doxorubicin DRUG

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

Also known as: Doxil

Treatment Arm

Doxorubicin DRUG

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

Also known as: Doxorubicin Hydrochloride

Treatment Arm

Anti-PD-1 monoclonal antibody DRUG

200 mg, d1, q3w

Also known as: Sintilimab

Treatment Arm

Radiotherapy RADIATION

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

Treatment Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Has\>5 cm lesions, or the lesions are determined to be borderline resectable or unresectable by a multidisciplinary consultation.
• Has imaging-confirmed localized lesions on the limbs or trunk without distant metastases.
• Experience primary tumor or local recurrence after surgery (disease-free survival more than 2 months after surgery)
• 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
• 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.)
• Fully informed and willing to provide written informed consent for the trial.

You may not qualify if:

• The presences of regional or distant metastases detected by imaging evaluation
• Patients with the following histological types: osteosarcoma, chordoma, classical chondrosarcoma, Kaposi's sarcoma, malignant mesothelioma, radiation-induced sarcomas.
• 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)
• 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.
• Uncontrolled hyperglycaemia or Coagulation disorder
• Active infection requiring systemic anti-infective therapy
• Previous major surgery within 2 weeks before enrolment (excluding minor operation such as diagnostic biopsy or peripherally inserted central catheter implantation)
• Known history of immunodeficiency diseases or active autoimmune disease requiring systemic treatment
• Female patients pregnant or breastfeeding, Male patients expecting to have babies

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

liposomal doxorubicin; Doxorubicin; spartalizumab; sintilimab; Radiotherapy

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Therapeutics

Study Officials

• Zhen Zhang, M.D, PH.D

  Fudan University

  PRINCIPAL INVESTIGATOR

• Wangjun Yan, 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: February 2, 2023
• First Posted: March 17, 2023
• Study Start: August 25, 2022
• Primary Completion: August 24, 2024
• Study Completion (Estimated): August 24, 2029
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

CN (1)