colorectal cancer
Conditions
Interventions
dose-expansion:SHR1701 and Surufatinib
dose-exploration :SHR1701 and Surufatinib
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1) 18-80 years of age; 2) ECOG score of 0-1; 3) Histologically confirmed diagnosis of advanced or metastatic colorectal cancer with at least one measurable lesion (assessed by the investigator according to RECIST 1.1); 4) have received at least 2 lines of standard chemotherapy regimens with imaging evidence of disease progression; for neoadjuvant or adjuvant therapy (chemotherapy or chemoradiotherapy), disease progression should be counted as first-line treatment if it occurs during or within 6 months after discontinuation of treatment (as assessed by the investigator according to RECIST1.1) 5) Expected survival > 12 weeks; 6) Normal major organ function and bone marrow function, meeting the following requirements: a. Hemoglobin = 90 g/L; (no transfusion within 14 days) b. absolute neutrophil count = 1.5×109/L c. Platelet count = 100×109/L d. Total bilirubin = 1.5 times the upper limit of normal (ULN) e. glutamic aminotransferase (ALT) and glutamic aminotransferase (AST) = 2.5 times ULN; if liver metastases are present, ALT and AST = 5 times ULN f. creatinine = 1.5 times ULN g. left ventricular ejection fraction (LVEF) = 50%; QTc < 450ms in men and < 470ms in women 7) International normalized ratio (INR) of prothrombin time = 1.5 and partial thromboplastin time (APTT) = 1.5 times ULN in patients not previously treated with anticoagulation. patients receiving full dose or parenteral anticoagulant therapy need to be on a stable dose of anticoagulant for at least 2 weeks prior to entry into clinical studies and have results of coagulation assay tests within the limits imposed by local therapy; 8) have recovered to CTCAE criteria = grade 1 (fully healed wounds if surgical) prior to entry for toxicity on prior therapy; 9) Women of childbearing potential must have a negative pregnancy test (serum or urine) result within 14 days prior to enrollment and voluntarily use an appropriate method of contraception during the observation period and for 3 months after the last administration of study drug and must be non-lactating; male subjects should be surgically sterilized or agree to use an appropriate method of contraception during the observation period and for 3 months after the last administration of study drug; 10) Patients voluntarily participate and sign an informed consent form and are expected to be compliant and able to cooperate with the study as required by the protocol;
Exclusion criteria
Exclusion criteria: 1) Participation in another interventional clinical trial within 4 weeks prior to enrollment; 2) Presence of other malignancies that remain to be treated within 30 days prior to enrollment 3) poorly controlled hypertension (persistent elevation of systolic blood pressure = 150 mmHg or diastolic blood pressure = 100 mmHg) even after pharmacological treatment 4) patients with uncontrolled cardiac clinical signs or conditions such as (1) NYHA class II or higher heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention 5) active bleeding within 3 months; arterial/venous thrombotic event within 6 months; presence of hereditary or acquired bleeding (e.g., coagulation disorders) or thrombotic tendency; current use or recent (10 days prior to start of study treatment) of full-dose oral or injectable anticoagulant or thrombolytic medication for therapeutic purposes; surgery (other than biopsy) within 4 weeks prior to study or surgical incision that has not complete healing; current or recent use (10 days prior to study) of aspirin (>325 mg/day) or dipyridamole, ticlopidine, clopidogrel and cilostazol; 6) Use of systemic corticosteroids or other systemic immunosuppressive drugs within 2 weeks prior to treatment. Initiation or anticipated need for immunosuppressive drugs during the trial (inhaled glucocorticoids, physiological replacement doses of glucocorticoids allowed); 7) History of immunodeficiency, including HIV seropositive test, other acquired, congenital immunodeficiency disorders, or history of organ transplantation; 8) presence of active hepatitis B (HBeAg positive and HBV DNA = 500 IU/mL), hepatitis C (hepatitis C antibody positive and HCV RNA above the lower limit of detection by analytical methods) 9) Persons with severe infections requiring antibiotic, antiviral or antifungal control 10) require concomitant use of known potent CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate intensity CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). An elution period of at least 2 weeks prior to the start of treatment with Surufatinib; 11) Concomitant use of a known potent CYP3A inducer (e.g. phenobarbital, phenytoin, rifampin, rifabutin, rifapentine, carbamazepine, nevirapine, oncolytic) or a moderately potent CYP3A inducer (e.g. bosentan, efavirenz, modafinil) is required. A minimum elution period of 5 weeks for phenobarbital or enzalutamide and 3 weeks for the other drugs before the start of treatment with Surufatinib; 12) Known hypersensitivity to any component of this test drug 13) a prior definite history of neurological or psychiatric disorders, including epilepsy and dementia 14) Known uncontrolled or symptomatic active central nervous system (CNS) metastases as evidenced by the presence of clinical signs, cerebral edema, spinal cord compression, cancerous meningitis, soft meningeal disease, and/or progressive growth 15) Patients who are unable to swallow the study drug and have multiple factors affecting drug uptake and absorption such as chronic diarrhea (including but not limited to irritable bowel syndrome, Crohn's disease, ulcerative colitis) and intestinal obstruction; 16) Other conditions that, in the opinion of the investigator, are not sui
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate;Progression-free survival;Overall survival;safety; | — |
Countries
China
Contacts
Public ContactYong Gao
Shanghai East Hospital
Outcome results
None listed