Patient case: 54-year-old male with malignant hyperthermia; genetic feature: RYR1

Clinical trial: A Study of XY0206 in Subjects With Advanced or Metastatic Solid Tumours

Summary: 1. To observe the safety and tolerability of oral XY0206 in patients with advanced/metastatic malignant solid tumor in China, and observe the drug dose limiting toxicity (DLT) to establish the maximum tolerated dose (MTD) in humans.
  2. To investigate the pharmacokinetic (PK) characteristics, pharmacodynamics (PD) characteristics, and PK/PD correlation of single and multiple doses of XY0206 in patients with advanced/metastatic malignant solid tumors to provide dose selection basis for clinical studies;
  3. To evaluate the effect of standard meal on main PK parameters of XY0206;
  4. To determine the metabolites of XY0206 in patients with advanced/metastatic malignant solid tumor.
  5. To explore the correlation between PK and QTcF.
  6. Preliminary investigates the effectiveness of XY0206 in patients with advanced/metastatic malignant solid tumors.


Eligibility: Inclusion Criteria:
  -  Patients must meet all of the following criteria before entering the group:
  1. Patients with advanced/metastatic malignant solid tumor (eg, non-small cell lung cancer, gastrointestinal stromal tumor, renal cell carcinoma, pancreatic cancer, etc.) who have been diagnosed by histology and cytology that standard treatment failure, no effective treatment or relapse after treatment;
  2. Patients have tumor lesions that can be measured or can be evaluated (1.1 versions of RECIST efficacy evaluation criteria);
  3. Age 18 to 70 years old (including upper and lower limits), male and female ( For patients participating in extended trials, the proportion of each sex is not less than 30%);
  4. ECOG≤ 2;
  5. The estimated survival period ≥ 3 months;
  6. 19≤BMI≤30, body mass index = weight (kg) /height 2 (m2);
  7. Liver function: glutamate transaminase (AST) <2.5×ULN, ALT <2.5 x ULN, total bilirubin <1.5 ×ULN;
  8. Blood potassium and serum sodium levels are within the normal range of the laboratory (if both the investigator and the medical monitor judge that the out-of-normal range results have no clinical significance, the patient can be enrolled; if the values can be controlled by drug during the screening period in normal range, the patient can be enrolled);
  9. Renal function: serum creatinine (Scr) ≤1.5×ULN or creatinine clearance rate (Ccr) >40mL/min. Ccr formula: male Ccr = [(140 - age) ×body weight (kg)] / [0.818 x Scr (μmol/L)], women Ccr = 0.85 x [(140 - age) × body weight (kg)] / [0.818 x Scr (μmol/L)];
  10. Blood routine: platelet count > 80 x 109/L, hemoglobin > 90g/L, neutrophils absolute count > 1.5 x 109/L;
  11. Urine routine: urine protein≤1.5×ULN;
  12. Coagulation function: global standardized ratio＜1.5;
  13. No other anti-tumor adjuvant therapy (including steroids with anti-tumor effects);
  14. Women of childbearing age and male patients are agree to adopt conventional, adequate and effective contraceptive measures during the entire study period and within 6 months after completion of the study;
  15. Subjects who are able to understand and are willing to sign the informed consent form, with the intention and ability to complete regular visits, treatment plans, laboratory tests and other trial procedures.
  Exclusion Criteria:
  -  Patients cannot participate in this clinical study if they meet any of the following conditions:
  1. Pregnant or lactating women;
  2. Human immunodeficiency virus (HIV) test positive;
  3. HBV or HCV infection activity is known to have abnormal liver function and need to receive antiviral drugs;
  4. Subjects were severe wounds, ulcers, or fractures when screened;
  5. History of uncontrolled epilepsy, central nervous system disease, or mental illness;
  6. Symptomatic or uncontrolled brain metastasis or meningeal disease;
  7. Poor drug control of diabetes or high blood pressure（In the case of optimal drug therapy, fasting blood glucose >7mmol/L, or blood pressure >150/100 mmHg）;
  8. Uncontrolled thyroid dysfunction;
  9. Continuation of arrhythmia and grade≥ 2 in NCI CTCAE V4.03, any level of atrial fibrillation;
  10. Heart ejection fraction (cardiac ultrasonography) is less than 50%;
  11. Patients with clinically significant QTc prolongation (men>450ms, women>470ms);
  12. Have a history of severe drug allergies（According to version 4.03 NCI CTCAE levels≥3 and may be allergic to investigation drug ingredients；Subject has been treated with sunitinib malate or allergy to sunitinib malate;
  13. Drugs（ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, dexamethasone, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, and phenobarbital, st. John's wort, etc ）or food（For example: grapefruit and food containing grapefruit）that has significant effects on the P450 metabolic pathway is being taken two weeks ago;
  14. Received any investigational drug treatment within 3 months before screening;
  15. Patients received anti-tumor therapy（chemotherapy, radiotherapy, biological therapy or hormone therapy） within 4 weeks before screening；Surgery was performed within 3 months before screening;
  16. The patient has any medical or psychiatric conditions that limit trial compliance, such as central nervous system (CNS) leukemia, active and uncontrolled bacterial infection, grade 3 or 4 bleeding, unstable angina, myocardial infarction, stroke or transient ischemic attack, pulmonary embolism, or non-catheter-related deep venous thrombosis, insulin-dependent diabetes mellitus (that is, type I diabetes), or non-insulin-dependent diabetes mellitus with signs of small vessel disease within 6 months prior to the study, known as adrenocortical insufficiency, malabsorption syndrome, and active autoimmune diseases;
  17. Other serious acute or chronic medical or psychiatric conditions, or abnormal results of laboratory shows that it may exacerbate the risks related to participating in the experiment or taking the investigational drug, or abnormal results of laboratory that may interfere with interpretation of test results. These conditions or abnormalities, in the opinion of investigator, make subject unfit to take part in the trial.

Relevance to patient case: not relevant