Clinical trial NCT05774275: The Combination of Radiotherapy, Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma
Official title: A Prospective Phase Ib/II Trial of Preoperative Radiotherapy Combined With Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: High-Risk Localized Soft Tissue Sarcoma
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-03-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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:
measure: Pathological Complete Response (pCR) and Near pCR Rate
timeFrame: The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.
measure: Non-Perfused Volume (NPV)
timeFrame: 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.
measure: Acute Adverse Events
timeFrame: through study completion, an average of 6 months.
measure: Wound Complications
timeFrame: Up to 120 days from the surgery.
measure: Local Control Rate
timeFrame: Up to 5 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Quality of Life (QoL) according to the Musculoskeletal Tumor Society (MSTS)
timeFrame: Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
measure: Quality of Life (QoL) according to the Toronto Extremity Salvage Score (TESS)
timeFrame: Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
measure: Quality of Life (QoL) according to the Short Form (SF)-36 questionnaires
timeFrame: Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhen Zhang, M.D, PH.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Wangjun Yan, M.D, PH.D
role: PRINCIPAL_INVESTIGATOR
References: