Chidamide Combined With Toripalimab in Sarcoma

NCT04025931 | Unknown Phase 2

• 1 other identifier: SunYat-senU-chidamide
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Soft tissue sarcoma is a relatively rare malignant tumor with an incidence of about 1-2/100,000. The best way to obtain evidence-based medical evidence is to participate in clinical trials with new drugs (especially targeted drugs and immunotherapy). Chidamide, an oral subtype-selective histone deacetylase inhibitor monotherapy was effective on the patients with hematological tumors by inhibiting HDAC activity and other ways, showing good anti-tumor activity. Histone deacetylase inhibitors (HDACi) may also reverse drug resistance or inefficiency of immunoassay inhibitors, and combination therapy has shown preliminary efficacy in a variety of tumors.Because of the poor prognosis of advanced soft tissue sarcoma, there is no standard second-line treatment. Therefore, we think it is necessary to explore the feasibility of combination of chidamide and Toripalimab monoclonal antibody in advanced, refractory and progressive soft tissue sarcoma after failure of standard treatment, and look forward to further improving the efficacy of soft tissue sarcoma.

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  Objective response rate is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

Secondary Outcomes (3)

• Progress free survival

  until Progressive Disease(PD) or death(up to 24 months)

• Overall Survival

  From randomization until death (up to 24 months)

• Disease Control Rate

  each 42 days up to intolerance the toxicity or PD (up to 24 months)

Study Arms (1)

chidamide combined with Toripalimab

EXPERIMENTAL

chidamide 30mg orally twice a week; 240 mg of toripalimab (fixed dose) every three weeks. Repeat every three weeks. Patients with disease control (CR + PR + SD) and tolerable adverse reactions continued to take medication until the researchers concluded that patients were not suitable to continue medication or the efficacy evaluation was disease progression (PD). No other antineoplastic treatment can be given during the treatment.

Drug: chidamide and toripalimab

Interventions

chidamide and toripalimab DRUG

The eligible patients with advanced soft tissue sarcoma were treated with chidamide combined with toripalimb. Chidamide 30mg orally twice a week; Toripalimab 240 mg (fixed dose) every three weeks. Repeat every three weeks. Patients with disease control (CR + PR + SD) and tolerable adverse reactions continued to take medication until the researchers concluded that patients were not suitable to continue medication or the efficacy evaluation was disease progression (PD). No other antineoplastic treatment can be given during the treatment.

chidamide combined with Toripalimab

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 this study and signed the informed consent;
• The pathology diagnosed with at least one measurable lesion according to RECIST 1.1 standard. The pathology includes synovial sarcoma, leiomyosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma, liposarcoma, fibrosarcoma, clear cell sarcoma, epithelioid sarcoma, malignant peripheral nerve sheath tumor, undifferentiated sarcoma, rhabdomyosarcoma, dermatofibrosareoma promberans, ewing's sarcoma /primary neural ectoderm tumors, desmoplastic small round cell tumor, inflammatory myofibroblastic sarcoma, malignant solitary fibroma. Except for chondrosarcoma, osteosarcoma, malignant mesothelioma, alveolar soft tissue sarcoma, gastrointestinal stromal tumor;
• Advanced sarcoma patients with refractory or distant metastasis after failure of first-line standard therapy;
• \~ 70 years old; ECOG PS score: 0\~1; Expected survival beyond 3 months;
• Adequate organ and bone marrow function, no serious hematopoietic dysfunction or heart, lung, liver, kidney, thyroid dysfunction and immune deficiency (no blood transfusion, granulocyte colony stimulating factor or other medical support was received within 14 days before the use of the research drug):
• Major organs functions should meet the following standards within 7 days before treatment:
• Blood routine examination standard (without blood transfusion within 14 days) :
• Hemoglobin (HB) ≥90g/L; The absolute value of neutrophils (ANC) ≥1.5×109/L; Platelet (PLT) ≥80 ×109/L.
• Biochemical examination shall meet the following standards:
• Total bilirubin (TBIL) ≤ 1.5 times ULN (Upper Limit Of Normal); alanine aminotransferase （ALT）and aspartate aminotransferase AST≤2.5 times ULN. If accompanied by liver metastasis, ALT and AST≤5 times ULN；Serum creatinine（Cr）≤1.5 times ULN or creatinine clearance rate (CCr)≥ 60ml/min； Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ normal low limit (50%).
• Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (+10%).
• Women of reproductive age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during and within 6 months after the study; Negative serum or urine pregnancy test within 7 days prior to study enrollment and must be non-lactating;
• Men should agree to use contraceptives during and within 6 months after the study period.

You may not qualify if:

• Patients who have previously used chidamide or other histone deacetylase inhibitors;
• Previous treatment with immunological checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.);
• Other malignancies that have occurred or are present at the same time within 5 years, except for cured cancers including carcinoma in situ of the cervix, non-melanoma skin cancer and superficial bladder tumor \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\];
• Start the study of systemic anti-cancer therapy within 28 days before treatment, including chemotherapy, immunotherapy, biotherapy (cancer vaccine, cytokines, or growth factors that control cancer).
• The patients received Chinese herbal medicine or Chinese patent medicine treatment within 7 days before the start of the study.
• Systemic anti-tumor therapy, including cytotoxic therapy, signal transduction inhibitors, and immunotherapy (or mitomycin C administration within 6 weeks before the treatment with the experimental drug), is planned within 4 weeks before enrollment or during the medication period of this study. In the first 4 weeks of enrollment, the patients were treated with field expanding radiotherapy (ef-rt) or the limited field radiotherapy designed to evaluate tumor lesions in the first 2 weeks of enrollment.
• Accompanied by pleural effusion or ascites, causing respiratory syndrome (CTCAE grade 2 dyspnea \[grade 2 dyspnea refers to shortness of breath when there is a small amount of activity; it affects instrumental daily life activities\]);
• Unrelieved toxic reactions caused by any previous treatment higher than CTCAE (4.1) level 1 or above, excluding hair loss;
• Patients with brain metastases with symptoms or with symptoms for less than 2 months;
• Patients with any severe and/or uncontrolled disease, including:
• )Patients with unsatisfactory blood pressure control (systolic blood pressure 150 mmHg, diastolic blood pressure 100 mmHg); 2)Patients with grade I or above myocardial ischemia or myocardial infarction, arrhythmia (including QTC 480ms) and grade II congestive heart failure (NYHA classification); 3)Active or uncontrolled severe infection (CTCAE grade 2 infection); 4)Cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral treatment; 5) Renal failure requires hemodialysis or peritoneal dialysis; 6) Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 7)Poor control of diabetes mellitus (FBG) \> 10mmol/L); 8)Urine routine test indicated urine protein ++, and confirmed the 24-hour urine protein quantitative \> 1.0g; 9)Patients with seizures requiring treatment;
• \. Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before enrollment;
• \. Patients with any signs of bleeding constitution or medical history, regardless of the severity; Patients with any bleeding or bleeding event CTCAE level 3 within 4 weeks before enrollment have unhealed wounds, ulcers or fractures;
• \. Hyperactive/venous thrombosis events within 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism;
• \. Patients with active ulcer, intestinal perforation and intestinal obstruction;

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-Sen Univerisity

Guangzhou, Guangdong, 510000, China

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; toripalimab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Xing Zhang, professor

CONTACT

020-87343383; zhangxing@sysucc.org.cn

Study Design

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

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 19, 2019
• Study Start: January 19, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

CN (1)