- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05774275
The Combination of Radiotherapy, Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma (RAPID)
A Prospective Phase Ib/II Trial of Preoperative Radiotherapy Combined With Chemotherapy and Immunotherapy in High-Risk Localized Soft Tissue Sarcoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Yan Wang, M.D, PH.D
- Phone Number: 18121299388
- Email: wangxyyan@sina.com
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 200032
- Recruiting
- Fudan University Shanghai Cancer Center
-
Contact:
- Zhen Zhang, M.D, PH.D
- Phone Number: 19521280960
- Email: zhen_zhang@fudan.edu.cn
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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. |
In phase Ib: 37.5 mg/m2, 30 mg/m2, d1, q3w; In phase II: recommended phase 2 dose (RP2D), d1, q3w.
Other Names:
75mg/m2, d1, q3w Doxorubicin hydrochloride will be administered if subject is allergic to Doxil.
Other Names:
200 mg, d1, q3w
Other Names:
BED=50-60Gy(α/β=10); Radiation dose depends on tumor characteristics and organs at risk.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
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.
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathological Complete Response (pCR) and Near pCR Rate
Time Frame: The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.
|
The proportion of subjects whose pathological response rate of tumor tissue in postoperative specimens is ≥90% after preoperative treatment.
|
The pathologic complete response (pCR) rate will be evaluated from surgical samples, immediately after surgery.
|
Non-Perfused Volume (NPV)
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.
|
The changes in tumour volume that are not enhanced in imaging images with contrast agent before and after treatment.
|
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
Time Frame: through study completion, an average of 6 months.
|
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).
|
through study completion, an average of 6 months.
|
Wound Complications
Time Frame: Up to 120 days from the surgery.
|
Postoperative incision healing, with reference to the Canadian study for grading of wound complications.
|
Up to 120 days from the surgery.
|
Local Control Rate
Time Frame: Up to 5 years
|
The proportion of subjects who recurred within the radiotherapy exposure field from initiation of treatment to the imaging assessment of all evaluable subjects.
|
Up to 5 years
|
Progression-Free Survival (PFS)
Time Frame: Up to 5 years
|
The time from initiation of treatment to PD or death from any cause.
|
Up to 5 years
|
Overall Survival (OS)
Time Frame: Up to 5 years
|
The time from initiation of treatment to death from any cause.
|
Up to 5 years
|
Quality of Life (QoL) according to the Musculoskeletal Tumor Society (MSTS)
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.
|
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) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
|
Quality of Life (QoL) according to the Toronto Extremity Salvage Score (TESS)
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.
|
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) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
|
Quality of Life (QoL) according to the Short Form (SF)-36 questionnaires
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.
|
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.
|
Quality of Life (QoL) will be evaluated at least five times: before treatment, at 3, 6, 12 and 24 months respectively after surgery.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wangjun Yan, M.D, PH.D, Fudan University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Sarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Antibodies
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
Other Study ID Numbers
- FDRT-2021-373-2676
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on High-Risk Localized Soft Tissue Sarcoma
-
Fudan UniversityRecruitingHigh-Risk Localized Soft Tissue SarcomaChina
-
Italian Sarcoma GroupFrench Sarcoma Group; Grupo Espanol de Investigacion en SarcomasActive, not recruitingLocalized High-risk Soft Tissue Sarcomas of the Extremities and Trunk Wall in AdultsSpain, Italy
-
Affiliated Hospital to Academy of Military Medical...UnknownHigh-risk Soft Tissue SarcomaChina
-
Samsung Medical CenterRecruitingUnresectable Localized Soft Tissue SarcomaKorea, Republic of
-
Grupo Espanol de Investigacion en SarcomasRecruitingAdvanced Solid Tumor | Advanced Soft-tissue Sarcoma | Advanced L-sarcomas | Other Advanced Sarcomas | Localized Soft-tissue SarcomaSpain
-
Ruijin HospitalRecruitingSoft Tissue Sarcoma | Radiotherapy | Anlotinib | High Risk of RecurrenceChina
-
Fudan UniversityUnknownSoft Tissue Sarcoma Adult | High Grade SarcomaChina
-
National Cancer Institute (NCI)CompletedRhabdomyosarcoma | Synovial Sarcoma | Ewing's Sarcoma | MPNST | High-risk SarcomaUnited States
-
H. Lee Moffitt Cancer Center and Research InstituteViewray Inc.RecruitingHigh Grade SarcomaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingSarcoma | Rhabdomyosarcoma | Adult Rhabdomyosarcoma | Childhood Alveolar Rhabdomyosarcoma | Childhood Embryonal Rhabdomyosarcoma | Childhood Botryoid-Type Embryonal Rhabdomyosarcoma | Localized Childhood Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma AJCC v7 | Stage II Adult Soft Tissue Sarcoma... and other conditionsUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
Clinical Trials on Pegylated Liposomal Doxorubicin
-
Sun Yat-sen UniversityUnknown
-
GlaxoSmithKlineCompletedNeoplasms, OvarianUnited States
-
MedSIRRoche Pharma AG; ExperiorCompleted
-
National Cancer Institute (NCI)CompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Breast Carcinoma | Estrogen Receptor Negative | HER2/Neu Negative | Progesterone Receptor Negative | Triple-Negative Breast Carcinoma | Male Breast Carcinoma | Stage IV Breast Cancer AJCC...United States
-
National Cancer Institute (NCI)CompletedDS Stage I Plasma Cell Myeloma | DS Stage II Plasma Cell Myeloma | DS Stage III Plasma Cell MyelomaUnited States
-
Fudan UniversityRecruiting
-
Cancer Institute and Hospital, Chinese Academy...CSPC Ouyi Pharmaceutical Co., Ltd.UnknownHER2-positive Breast CancerChina
-
University of ArizonaTerminatedBreast CancerUnited States
-
Spanish Breast Cancer Research GroupSchering-PloughCompleted
-
European Organisation for Research and Treatment...CompletedLymphomaGermany, Switzerland, Israel, United Kingdom, Austria, Italy