Clinical trial NCT03658070: A Study of XY0206 in Subjects With Advanced or Metastatic Solid Tumours
Official title: A Phase I Open and Multiple Ascending Dose Study to Assess the Safety、Tolerability、Pharmacokinetics and Pharmacodynamic Characteristics of XY0206 in Subjects With Chinese Advanced or Metastatic Solid Tumours
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumours
Lead sponsor: Shijiazhuang Yiling Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
Collaborators: name: Tigermed Consulting Co., Ltd
First posted: 2018-09-05
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 criteria: Inclusion Criteria:

* Patients must meet all of the following criteria before entering the group:

  1. Patients with advanced/metastatic solid tumor (such as non-small cell lung cancer, gastrointestinal stromal tumor, renal cell carcinoma, pancreatic cancer, etc.) who have failed standard treatment with histological or cytological diagnosis, have no effective treatment, or have relapsed after treatment.
  2. Patients with measurable or evaluable tumor lesions (1.1 version of RECIST efficacy evaluation criteria).
  3. The age is 18\~70 years old (including upper and lower limit), and there is no restriction on male and female (for participating in the extended trial)Of patients with a sex ratio of not less than 30%).
  4. Physical condition ECOG≤2.
  5. Expected survival ≥3 months.
  6. BMI at 19≤BMI≤30, BMI = weight (kg)/height 2 (m2).
  7. Liver function: AST \<2.5×ULN, ALT\<2.5×ULN, total bilirubin \<1.5×ULN.
  8. Blood biochemistry: Serum potassium and sodium levels are within the range of normal laboratory values (if researchers and physiciansThe overseer assesses results beyond the normal range to be of no clinical significance and the patient canInto the group; If the drug can be controlled within the normal range during the screening period, the patient canTo enroll).
  9. Renal function: serum creatinine (Scr) ≤1.5×ULN or calculated creatinine clearance rate(Ccr) \>60mL/min Ccr calculation formula: male Ccr=\[(140- age)× weight(kg)\] / \[0.818 x Scr (mu mol/L)\], women Ccr = 0.85 x \[(140 - age) by weight(kg)\] / \[0.818 x Scr (mu mol/L)\].
  10. blood routine: platelet count of \> 80×109/L, hemoglobin of \> 90g/L, neutrophil pair count of \> 1.5×109 /L.
  11. Urine routine: urinary protein - or 1+, or 24-hour urinary protein \<1 g \[Note: if due to urinary tractTransient abnormalities of the above urinary protein due to infection and other causes returned to normal after retesting.You can also consider enrolling; Subjects without proteinuria symptoms may also be considered for inclusion.
  12. Coagulation function: International standardized ratio \< 1.5.
  13. No other antitumor concomitant therapy (including steroids with antitumor effects).
  14. Women of childbearing age and men agreed to use it throughout the study period and within 6 months after completion of treatmentRegular contraception that is effective enough.
  15. Understand and voluntarily sign written informed consent, and have the willingness and ability to complete regular visits and treatmentTreatment planning, laboratory examination and other test procedures.

Exclusion Criteria:

* Patients cannot participate in this clinical study if they meet any of the following conditions:

  1. Pregnant or lactating women.
  2. Tested positive for human immunodeficiency virus (HIV).
  3. The active period of HBV or HCV infection is known to be associated with abnormal liver function, and antiviral drugs are required.
  4. Severe trauma, ulcer or fracture at screening time.
  5. A history of uncontrolled epilepsy, central nervous system disease or mental illness.
  6. Symptomatic or uncontrolled brain metastases or meningeal diseases.
  7. diabetes or hypertension with poor drug control (under optimal drug treatment, fasting blood glucose \>7mmol/L, or blood pressure \> 150/100mmhg).
  8. Uncontrolled thyroid dysfunction.
  9. Persistent arrhythmias of version 4.03 or above, NCI CTCAE level ≥2, atrial fibrillation of any level.
  10. Cardiac ejection fraction (ECHOcardiography) below 50%.
  11. patients with clinically significant prolonged history of QTc (\>450ms for male and \>470ms for female).
  12. Have a history of severe drug allergy (NCI CTCAE level ≥3 according to version 4.03 or above) and may be allergic to test drug ingredients; Has been treated with or is allergic to sunitinib malate.
  13. for the first time to give medicine taken within 4 weeks before have significant effects on P450 metabolic pathway of drugs (for example: ketoconazole, itraconazole, clarithromycin, aza that wei, indiana that wei, naphthalene sanzuotong, that of the wei and the wey, ShaKui the wey, terry toxin, voriconazole, dexamethasone, phenytoin, carbamazepine, rifampicin, dean, rifampicin and dean at the cloth, phenobarbital, st. John's wort, etc.) or to eat within 48 h before delivery of P450 metabolic enzyme pathways have a significant impact on food (such as grapefruit and food containing grapefruit).
  14. Received any experimental drug therapy within 6 weeks prior to initial administration.
  15. for the first time six weeks before the treatment, patients treated with anti-tumor therapy (chemotherapy, radiation therapy, biological therapy, or hormone therapy) (note: for anti-tumor small molecules targeting drugs, if the patient before the first test drugs, always use small molecules targeting drug has cleared more than 5 half-life, the patient may also be considered into the group\]. Surgery was performed within 14 weeks prior to the first administration.
  16. patients have any limit test compliance of medical or psychiatric conditions, such as the central nervous system (CNS) leukemia, active control of bacterial infection, 3, or 4 bleeding, unstable angina, myocardial infarction, stroke or transient ischemic attack, pulmonary embolism, or into the group of six months before the test of catheter-related deep vein thrombosis, insulin-dependent diabetes mellitus (namely, type 1 diabetes), or non insulin-dependent diabetes but there were signs of small vascular disease, Adrenocortical dysfunction is known, malabsorption syndrome is known, and active autoimmune diseases are known.
  17. Other severe acute or chronic medical or psychiatric conditions, or laboratory test abnormalities that may exacerbate the risks associated with participating in or taking test drugs, or that may interfere with the interpretation of test results. These conditions or abnormalities may be determined by the investigator to make the patient unfit to participate in the trial.

Primary outcomes:
measure: DLT
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: AE
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: ADR
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: SAE
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Blood routine
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Urine routine
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Stool routine
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Blood biochemistry
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Coagulation function
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: 12 lead ecg
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Body temperature
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Blood pressure
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Heart rate
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Breathing
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: General condition
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Skin
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Head
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Eyes
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Ears
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Nose
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Throat
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Heart
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Lung
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Chest
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Abdomen
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Limbs
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Nerves
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Back/spine
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
measure: Lymph nodes
timeFrame: from the start of the medication to the end of the study or 28 days after cessation of medication
Secondary outcomes:
measure: AUCinf
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: AUC0-24h
timeFrame: single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
measure: AUC0-72h
timeFrame: single dose phase:up to 72 hours
measure: AUC0-120h
timeFrame: single dose phase:up to 120 hours
measure: Peak Plasma Concentration (Cmax)
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: CL/F
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Tmax
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Cmin,ss
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Cmax,ss
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Cav,ss
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: PTF
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: RAUC1
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: RAUC2
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: RCmax
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Kel
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: t1/2
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Vz/F
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: AUC_%Extrap
timeFrame: single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
measure: Ae0-24h
timeFrame: single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
measure: Fe0-24h
timeFrame: single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
measure: Ae0-72h
timeFrame: single dose phase:up to 72 hours
measure: Fe0-72h
timeFrame: single dose phase:up to 72 hours
measure: Ae0-72h stool
timeFrame: single dose phase:up to 72 hours
measure: CLr
timeFrame: single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
measure: Exploring the relative baseline change percentage of biomarkers (soluble VEGFR2).
timeFrame: single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
measure: Complete response rate (CRR)
timeFrame: through study completion,such as 30 months.
measure: Partial response rate (PRR)
timeFrame: through study completion,such as 30 months.
measure: Objective response rate (ORR)
timeFrame: through study completion,such as 30 months.
measure: Progression-free survival (PFS)
timeFrame: through study completion,such as 30 months.
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
city: Haikou
country: China
facility: The First Affiliated Hospital of Hainan Medical College
state: Hainan
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Binghe Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: