Back to resultsThe Combination of Radiotherapy，Surufatinib and Sintilimab in High-Risk Localized Soft Tissue Sarcoma (IRIS)
Primary Purpose
High-Risk Localized Soft Tissue Sarcoma
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Surufatinib
Sintilimab
Radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for High-Risk Localized Soft Tissue Sarcoma
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Pregnant or lactating women Allergic to any component of the therapy
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 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.
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.
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 the start 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
1. Study Identification
Unique Protocol Identification Number
NCT05839275
Brief Title
The Combination of Radiotherapy，Surufatinib and Sintilimab in High-Risk Localized Soft Tissue Sarcoma
Acronym
IRIS
Official Title
A Prospective Phase Ib/II Trial of Radiotherapy Combined With Tyrosine Kinase Inhibitor and Immune Checkpoint Inhibitor in High-Risk Localized Soft Tissue Sarcoma (IRIS)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
July 31, 2024 (Anticipated)
Study Completion Date
July 31, 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, 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.
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 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.
Intervention Type
Drug
Intervention Name(s)
Surufatinib
Intervention Description
In phase Ib: 250mg, 200mg, d1-21，qd; In phase II: recommended phase 2 dose (RP2D), d1-21，qd.
Intervention Type
Drug
Intervention Name(s)
Sintilimab
Intervention Description
200mg, 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.
Starts at the begin of the second cycle of systemic therapy (week 4 of the therapy).
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.
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 in week18-21.
Title
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
From the beginning of treatment to 90 days after the end of the last treatment.
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 the start of treatment to the imaging assessment of all evaluable subjects.
Time Frame
From the start of treatment to local recurrence, 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
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Pregnant or lactating women
Allergic to any component of the therapy
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
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，Surufatinib and Sintilimab in High-Risk Localized Soft Tissue Sarcoma
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