Combining chidamide and toripalimab for treating advanced sarcoma

A Single-arm, Multi-center, Open, Phase II Study of Chidamide Combined With Toripalimab in Refractory and Advanced Soft-tissue Sarcoma

This study is testing if combining two medications, chidamide and toripalimab, can help people with advanced soft tissue sarcoma who haven't responded to other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 74 (estimated)
• Ages: 14 Years to 70 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Toripalimab, Pembrolizumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT04025931 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining chidamide, a histone deacetylase inhibitor, with toripalimab, a PD-1 monoclonal antibody, in patients with advanced soft tissue sarcoma who have not responded to standard treatments. The study aims to evaluate the safety and efficacy of this combination therapy in patients with various subtypes of sarcoma. By targeting different pathways involved in tumor growth and immune evasion, the trial seeks to improve patient outcomes in a population with limited treatment options. Participants will be monitored for tumor response and overall survival.

Who should consider this trial

Good fit: Ideal candidates include patients aged 14 to 70 with advanced, refractory soft tissue sarcoma who have measurable lesions and have failed first-line therapy.

Not a fit: Patients with chondrosarcoma, osteosarcoma, or other specific sarcoma types excluded from the study may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced sarcoma, potentially improving survival rates and quality of life.

How similar studies have performed: Previous studies have shown some success with immunotherapy in sarcoma, but this specific combination approach is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Patients voluntarily participated in this study and signed the informed consent;
2. 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;
3. Advanced sarcoma patients with refractory or distant metastasis after failure of first-line standard therapy;
4. 14 \~ 70 years old; ECOG PS score: 0\~1; Expected survival beyond 3 months;
5. 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):
6. 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%).
7. Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (+10%).
8. 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;
9. Men should agree to use contraceptives during and within 6 months after the study period.

Exclusion Criteria:

1. Patients who have previously used chidamide or other histone deacetylase inhibitors;
2. Previous treatment with immunological checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.);
3. 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)\];
4. 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).
5. The patients received Chinese herbal medicine or Chinese patent medicine treatment within 7 days before the start of the study.
6. 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.
7. Accompanied by pleural effusion or ascites, causing respiratory syndrome (CTCAE grade 2 dyspnea \[grade 2 dyspnea refers to shortness of breath when there is a small amount of activity; it affects instrumental daily life activities\]);
8. Unrelieved toxic reactions caused by any previous treatment higher than CTCAE (4.1) level 1 or above, excluding hair loss;
9. Patients with brain metastases with symptoms or with symptoms for less than 2 months;
10. Patients with any severe and/or uncontrolled disease, including:

1)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;

11. Received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before enrollment;

12. 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;

13. Hyperactive/venous thrombosis events within 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep venous thrombosis and pulmonary embolism;

14. Patients with active ulcer, intestinal perforation and intestinal obstruction;

15. Have a history of mental drug abuse and cannot quit or have mental disorder;

16. Participated in clinical trials of other anti-tumor drugs within 28 days before enrollment;

17.According to the judgment of the researcher, there are those who seriously endanger the safety of patients or affect the patients' completion of the study.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-Sen Univerisity — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Xing Zhang, professor

Conditions Sarcoma