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

Primary Purpose

High-Risk Localized Soft Tissue Sarcoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Pegylated Liposomal Doxorubicin
Doxorubicin
Anti-PD-1 monoclonal antibody
Radiotherapy
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High-Risk Localized Soft Tissue Sarcoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Pathological Complete Response (pCR) and Near pCR Rate
The proportion of subjects whose pathological response rate of tumor tissue in postoperative specimens is ≥90% after preoperative treatment.
Non-Perfused Volume (NPV)
The changes in tumour volume that are not enhanced in imaging images with contrast agent before and after treatment.
Acute Adverse Events
The toxic reactions are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Edition 5 (NCI-CTCAE V. 5).
Wound Complications
Postoperative incision healing, with reference to the Canadian study for grading of wound complications.
Local Control Rate
The proportion of subjects who recurred within the radiotherapy exposure field from initiation of treatment to the imaging assessment of all evaluable subjects.
Progression-Free Survival (PFS)
The time from initiation of treatment to PD or death from any cause.
Overall Survival (OS)
The time from initiation of treatment to death from any cause.
Quality of Life (QoL) according to the Musculoskeletal Tumor Society (MSTS)
The Musculoskeletal Tumor Society (MSTS) is a measure of physical function across 7 items, including pain, range of motion, strength, joint stability, joint deformity, emotional acceptance, and overall function. Each item is scored from 0(worst) to 5(best) with a maximum possible score of 35, which is converted to a scale from 0 to 100 points.
Quality of Life (QoL) according to the Toronto Extremity Salvage Score (TESS)
The Toronto Extremity Salvage Score (TESS) is a self-administered questionnaire evaluating possible limitations in physical activity. A total of 30 questions are included in the TESS, and the degree of disability is rated from 0 (complete disability) to 5 (no functional impairment) in each item.
Quality of Life (QoL) according to the Short Form (SF)-36 questionnaires
The Short Form (SF)-36 questionnaires is a 36-item health survey status which is composed of the following eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each of these domains can be rated from 0 (worst) to 100 (best). The final SF-36 score is converted to a 0-100 points range scale.

Full Information

First Posted
February 2, 2023
Last Updated
March 15, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05774275
Brief Title
The Combination of Radiotherapy, Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma
Acronym
RAPID
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 25, 2022 (Actual)
Primary Completion Date
August 24, 2024 (Anticipated)
Study Completion Date
August 24, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-Risk Localized Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pegylated Liposomal Doxorubicin
Other Intervention Name(s)
Doxil
Intervention Description
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
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Doxorubicin Hydrochloride
Intervention Description
75mg/m2, d1, q3w Doxorubicin hydrochloride will be administered if subject is allergic to Doxil.
Intervention Type
Drug
Intervention Name(s)
Anti-PD-1 monoclonal antibody
Other Intervention Name(s)
Sintilimab
Intervention Description
200 mg, d1, q3w
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
BED=50-60Gy(α/β=10); Radiation dose depends on tumor characteristics and organs at risk.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
The objective response rate (ORR) will be evaluated before surgery, which will be scheduled 5-12 weeks after the last fraction of radiotherapy.
Secondary Outcome Measure Information:
Title
Pathological Complete Response (pCR) and Near pCR Rate
Description
The proportion of subjects whose pathological response rate of tumor tissue in postoperative specimens is ≥90% after preoperative treatment.
Time Frame
The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.
Title
Non-Perfused Volume (NPV)
Description
The changes in tumour volume that are not enhanced in imaging images with contrast agent before and after treatment.
Time Frame
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.
Title
Acute Adverse Events
Description
The toxic reactions are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Edition 5 (NCI-CTCAE V. 5).
Time Frame
through study completion, an average of 6 months.
Title
Wound Complications
Description
Postoperative incision healing, with reference to the Canadian study for grading of wound complications.
Time Frame
Up to 120 days from the surgery.
Title
Local Control Rate
Description
The proportion of subjects who recurred within the radiotherapy exposure field from initiation of treatment to the imaging assessment of all evaluable subjects.
Time Frame
Up to 5 years
Title
Progression-Free Survival (PFS)
Description
The time from initiation of treatment to PD or death from any cause.
Time Frame
Up to 5 years
Title
Overall Survival (OS)
Description
The time from initiation of treatment to death from any cause.
Time Frame
Up to 5 years
Title
Quality of Life (QoL) according to the Musculoskeletal Tumor Society (MSTS)
Description
The Musculoskeletal Tumor Society (MSTS) is a measure of physical function across 7 items, including pain, range of motion, strength, joint stability, joint deformity, emotional acceptance, and overall function. Each item is scored from 0(worst) to 5(best) with a maximum possible score of 35, which is converted to a scale from 0 to 100 points.
Time Frame
Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
Title
Quality of Life (QoL) according to the Toronto Extremity Salvage Score (TESS)
Description
The Toronto Extremity Salvage Score (TESS) is a self-administered questionnaire evaluating possible limitations in physical activity. A total of 30 questions are included in the TESS, and the degree of disability is rated from 0 (complete disability) to 5 (no functional impairment) in each item.
Time Frame
Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
Title
Quality of Life (QoL) according to the Short Form (SF)-36 questionnaires
Description
The Short Form (SF)-36 questionnaires is a 36-item health survey status which is composed of the following eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each of these domains can be rated from 0 (worst) to 100 (best). The final SF-36 score is converted to a 0-100 points range scale.
Time Frame
Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Wang, M.D, PH.D
Phone
18121299388
Email
wangxyyan@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhen Zhang, M.D, PH.D
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wangjun Yan, M.D, PH.D
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhen Zhang, M.D, PH.D
Phone
19521280960
Email
zhen_zhang@fudan.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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