Toripalimab Combined With CAV/IE Regimen

NCT04589741 | Recruiting Phase 2

• 1 other identifier: Toripalimab plus chemotherapy
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study was to investigate the efficacy and safety of CAV/IE chemotherapy combined with toripalimab versus CAV/IE chemotherapy alone in the treatment of patients with advanced or unresectable bone and soft tissue sarcomas who failed in standard treatment.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate, ORR

  The percentage of patients with complete remission and partial remission in patients with evaluable curative effect.

  up to 24 months

Secondary Outcomes (3)

• Progression-free survival, PFS

  Up to 24 months

• Disease-free surviva, DFS

  Up to 24 months

• Overall survival, OS

  Up to 24 months

Study Arms (2)

toripalimab combined with CAV/IE regimen

EXPERIMENTAL

toripalimab combined with CAV/IE regimen in patients with advanced or unresectable bone and soft tissue sarcomas who failed standard treatment

Drug: Toripalimab Combined With CAV/IE chemotherapy; Drug: CAV/IE alternate chemotherapy

CAV/IE chemotherapy alone

PLACEBO COMPARATOR

CAV/IE chemotherapy alone in patients with advanced or unresectable bone and soft tissue sarcomas who failed standard treatment

Drug: Toripalimab Combined With CAV/IE chemotherapy; Drug: CAV/IE alternate chemotherapy

Interventions

Toripalimab Combined With CAV/IE chemotherapy DRUG

CAV/IE regimen alternate chemotherapy (regimen 1: CTX 1.2mg/m2 D1 + ADM 50mg/m2 D1 + VCR 1.4mg/m2 D1 and scheme 2: IFO 1.5g/m2 D1-5 + vp-16 90mg / m2 D1-5, IV drip). Regimen 1 and 2 were performed alternately, with a cycle of 3 weeks; The patients were treated with toripalimab (240mg, 6ml) intravenously every 3 weeks; If doxorubicin has reached the upper limit or reduced cardiac toxicity, liposome adriamycin (50mg/m2) or IE regimen can be used After 6 courses of treatment, patients with disease control (CR + PR + SD) and tolerable adverse reactions were treated continuously. The study was completed when the researchers considered that the patients were not suitable for continuous medication or the efficacy evaluation was disease progression (PD). No other anti-tumor treatment can be carried out during the treatment.

CAV/IE chemotherapy alone; toripalimab combined with CAV/IE regimen

CAV/IE alternate chemotherapy DRUG

CAV/IE alternate chemotherapy (regimen1: CTX 1.2mg/m2 D1 + ADM 50mg/m2 D1 + VCR 1.4mg/m2 D1 and regimen2: IFO 1.5g/m2 D1-5 + VP-16 90mg/m2 D1-5, IV drip), regimen 1 and 2 were performed alternately, with a cycle of 3 weeks. Patiens with disease control (CR+PR+SD) and tolerable adverse reactions were treated continuously with a maximum of 8-10 cycles. If doxorubicin has reached the upper limit or reduced cardiac toxicity, liposome adriamycin (≥ 60 years old: 35mg/m2, \< 60 year old: 40mg/m2) or IE regimen can be used. The study was completed when the researchers considered that the patients were not suitable for continuous medication or the efficacy evaluation was disease progression (PD). No other anti-tumor treatment can be carried out during the treatment.

CAV/IE chemotherapy alone; toripalimab combined with CAV/IE regimen

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients voluntarily participated in the study and signed informed consent;
• For all advanced or non resectable bone and soft tissue sarcomas confirmed by pathology, the standard treatment failed or there was no standard treatment. They were mainly synovial sarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, liposarcoma, fibrosarcoma, clear cell sarcoma, angiosarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undiffertiated sarcoma, bone sarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, myofibroblastic sarcoma, malignant solitary fibroma, postradiation sarcoma,etc. But the pathological subtypes without standard treatment can be treated as first-line treatment, including but not limited to postradiation sarcoma, dedifferentiated / pleomorphic liposarcoma, clear cell sarcoma, etc., except for the following types: well differentiated liposarcoma, malignant mesothelioma, gastrointestinal stromal tumor, etc;
• Advanced patients with unresectable lesions or lymph nodes or distant metastasis assessed by imaging;
• In the past three months, there was at least one measurable target lesion according to RECIST version 1.1 standard, and it can be accurately measured by magnetic resonance imaging (MRI) or computer tomography (CT) in at least one direction (the maximum diameter needs to be recorded), with conventional CT ≥ 20 mm or spiral CT ≥ 10 mm.
• They were 14-70 years old; ECOG PS score: 0-1; the expected survival time was more than 3 months;
• Within 7 days before treatment, the main organ functions met the following criteria:
• (1) Blood routine examination standard (without blood transfusion within 14 days)
• ① Hemoglobin (HB) ≥ 90g / L;
• The absolute value of neutrophil (ANC) ≥ 1.5 × 109 / L;
• Platelet (PLT) ≥ 80 × 109 / L.
• (2) Biochemical examination should meet the following standards:
• ① Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN);
• Alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤ 2.5uln; ALT and AST ≤ 5uln with liver metastasis
• ③ Serum creatinine (CR) ≤ 1.5uln or creatinine clearance rate (CCR) ≥ 60ml / min;
• (3) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ the lower limit of normal value (50%).

You may not qualify if:

• \) Patients who had previously received anti-PD-1 / PD-L1 antibody therapy.
• \) Other malignancies occurred or were present within 5 years, except for cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor \[ta (non invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\];
• \) The patients with thyroid dysfunction after the best drug treatment;
• \) Systemic anti-tumor therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks prior to the trial drug treatment) was planned within 4 weeks before enrollment or during the study period. Over extended field radiotherapy was performed within 4 weeks before admission or limited field radiotherapy was performed within 2 weeks before grouping;
• \) With pleural effusion or ascites, it causes respiratory syndrome (≥ CTC AE grade 2 dyspnea \[grade 2 dyspnea refers to shortness of breath with a small amount of activity; it affects instrumental activities of daily living\]);
• \) Any unrelieved toxic reaction higher than CTC AE (4.01) grade 1 or above caused by previous treatment, excluding alopecia;
• \) Patients with any severe and / or uncontrolled disease, including:
• Patients with poor blood pressure control (SBP ≥ 150 mmHg, DBP ≥ 100 mmHg);
• Patients with myocardial ischemia or myocardial infarction of grade I or above, arrhythmia (including QTc ≥ 480ms) and congestive heart failure (NYHA) grade ≥ 2;
• Active or uncontrolled severe infection (≥ CTC AE Level 2 infection);
• Chronic liver disease, decompensated liver disease or decompensated hepatitis;
• Renal failure needs hemodialysis or peritoneal dialysis;
• Poor control of diabetes mellitus (FBG \> 10mmol / L);
• Urine routine examination showed that urine protein was ≥ + +, and 24-hour urine protein was more than 1.0 G;
• Patients with epilepsy and need treatment;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Xing Zhang

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xing Zhang

CONTACT

02087343383; zhangxing@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of department of medical sarcoma and melanoma,Principal Investigator,Clinical Professor

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 19, 2020
• Study Start: October 23, 2020
• Primary Completion: January 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 9, 2024

Record last verified: 2024-01

Locations

CN (1)