Advanced highly differentiated/dedifferentiated liposarcoma
Conditions
Interventions
Dose reduction group:SPH4336 +cadonilimab
Dose expansion group:SPH4336
Dose expansion group:cadonilimab
Dose expansion group:SPH4336+cadonilimab
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria Participants must meet all of the following criteria in order to be selected for this study: (1) The subjects voluntarily participated in this study and signed an informed consent form. (2) At the time of signing the informed consent form, the age is = 18 and = 75 years old, regardless of gender. (3) The ECOG score is 0-1 points (amputees who do not meet the ECOG score requirements need to use KPS re evaluation, and those who score = 70 points can be included in the group). (4) The expected survival period is = 3 months. (5) Patients with advanced solid tumor (including but not limited to patients with advanced well differentiated/dedifferentiated Liposarcoma, etc.) who cannot be treated by radical surgery/other local treatment and who are included in the group with pathological diagnosis in the dose decreasing stage, shall meet at least one of the following conditions: a) Invalid after standard treatment. b) Unable to tolerate standard treatment. c) There is no standard treatment method. d) Standard treatment without economic conditions. e) The patient refused to receive standard treatment. (6) In the dose expansion stage, patients with recurrent or metastatic advanced well differentiated/dedifferentiated Liposarcoma who cannot undergo radical surgery/other local treatment and are confirmed pathologically must also have evidence of disease progression within 6 months before the first administration of the study drug, And have previously received = 2 systemic drugs (these two drugs can be used in combination or alone, which must include anthracyclines, while other drugs can include arotinib, etc.) for treatment failure. *Treatment failure refers to the progression or intolerance of the disease during the treatment period or within 6 months from the last medication. (7) According to the RECIST v1.1 standard, subjects in the dose extension stage need to have at least one measurable lesion. Lesions that have previously received radiotherapy or other local treatments are generally not selected as measurable lesions unless it is confirmed that the lesion has progressed before enrollment. (8) The laboratory examination results before starting the study treatment meet the following organ functional requirements: a) Bone marrow function: Absolute value of neutrophils = 1.5 × 109/L (no granulocyte Colony-stimulating factor treatment within 7 days before laboratory examination); Platelets = 100 × 109/L (without transfusion of platelets or platelet growth factors within 7 days prior to laboratory examination); Hemoglobin = 90 g/L (no blood transfusion or use of erythropoietin within 7 days before laboratory examination). b) Liver function: Albumin = 30 g/L (no albumin infusion within 7 days prior to laboratory examination); Total bilirubin = 1.5 × Upper limit of normal value (ULN) (Gilbert's syndrome subjects can be = 3 × ULN); ALT, AST, ALP = 2.5 × ULN (ALT or AST = 5 in the presence of liver metastasis) × ULN; When there is bone metastasis, ALP = 5 × ULN). c) Renal function: serum creatinine = 1.5 × Calculate creatinine clearance rate (CrCl) = 60mL/min/1.73 m2 using ULN or Cockcroft Fault formula method. d) Coagulation function: International standardized ratio (INR) = 1.5, activated partial thromboplastin time (APTT) = 1.5 × ULN (applicable to unused anti (9) Prior to the start of the study treatment, the peripheral neurotoxicity response to previous anti-tumor drug treatment has returned to = 2 levels, and other reversible t
Exclusion criteria
Exclusion criteria: Exclusion criteria Subjects who meet any of the following criteria are not eligible for inclusion in this study: (1) I have received any CDK4/6 inhibitors in the past. (2) The patients with known central nervous system metastasis (those who have not transferred to the brain stem or meninges and who are Asymptomatic after treatment and have been stable from the study treatment for = 3 months can be included). (3) Within 28 days prior to the start of the study, chemotherapy, biological therapy, immunotherapy, and other anti-tumor drug treatments were received. The specific exclusion criteria are as follows: a) Nitroso urea or Mitomycin C treatment was received within 6 weeks before starting the study treatment. b) Oral fluorouracil and small molecule targeted drugs were received within 2 weeks before the start of the study treatment. (4) At the time of signing the informed consent, he was still receiving traditional Chinese patent medicines and simple preparations with anti-tumor indications. (5) I underwent surgery within 28 days before starting the study and did not recover from adverse reactions during the surgery. Or plan to carry out surgical treatment for advanced solid tumors (including Liposarcoma) during the study period. (6) There was a history of other malignant tumors within 5 years before starting the study treatment (except cured basal cell skin cancer, cervical Carcinoma in situ, thyroid papillary carcinoma, etc.). (7) There are active autoimmune diseases that require systematic treatment within 2 years prior to the start of the study, or the researcher determines the existence of autoimmune diseases that may recur or plan treatment. However, subjects who meet the following conditions can be enrolled: a) Skin diseases that do not require systematic treatment (such as Vitiligo, alopecia, psoriasis or eczema); b) Hypothyroidism caused by autoimmune Thyroiditis requires only a stable dose of hormone replacement therapy; c) Type I diabetes requiring only a stable dose of insulin replacement therapy; d) Childhood asthma has completely relieved, and no intervention is required in adulthood; e) Researchers have determined that the disease will not recur without external triggering factors. (8) There are diseases that need to be treated with systemic Corticosteroid (>10 mg prednisone daily or equivalent) or other immunosuppressive drugs within 2 weeks before the first start of the study treatment and during the study treatment. However, subjects who meet the following conditions can be enrolled: a) Local use of Corticosteroid, nasal sprays and inhaled Sex hormone. b) Glucocorticoids as pretreatment for infusion related reactions or allergic reactions (such as medication before CT examination) c) Relevant replacement therapy is being carried out, such as Thyroxine, insulin, physiological Corticosteroid replacement therapy with renal or pituitary dysfunction. d) Low dose Corticosteroid was used to treat orthostatic Hypotension. (9) The clinically significant cardio cerebral Vascular disease has one of the following conditions: a) I have experienced ischemic stroke (lacunar cerebral embolism) or severe thromboembolic disease within 6 months before starting the study treatment. b) Myocardial infarction, unstable angina pectoris, congestive heart failure, and severe heart rate abnormalities occurred within 6 months before starting the study treatment. c) Prior to the start of the study treatment, there was a NYHA cardiac insufficiency r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose reduction stage: tolerance;Dose extension stage: Investigator evaluated progression free survival (PFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| 12 week PFS rate (PFR);Dose reduction stage: progression free survival (PFS); Total survival time (OS);Objective response rate (ORR) evaluated by researchers;Disease control rate (DCR) evaluated by researchers;Investigator evaluated duration of relief (DoR);Pharmacokinetic (PK) characteristics of SPH4336;Safety such as vital signs, physical examinations, adverse events, clinical laboratory test results, etc; | — |
Countries
China
Contacts
Public ContactJiang Yu
West China Hospital, Sichuan University
Outcome results
None listed