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

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

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.

Study Overview

• Status: Unknown
• Conditions: Advanced or Metastatic Solid Tumours
• Intervention / Treatment: Drug: XY0206

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College
      • Contact: binghe xu, MD; Phone Number: 086-010-87788826; Email: xubinghe@medmail.com.cn
      • Principal Investigator: binghe xu, MD
  • Hainan
    • Haikou, Hainan, China, 570102
      • Not yet recruiting
      • The First Affiliated Hospital of Hainan Medical College
      • Contact: Jinsheng Wu, MD; Phone Number: 086-13707599070; Email: wjs7911@126.com
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Not yet recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Da Jiang, MD; Phone Number: 086-13933191980; Email: jiangda139@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Not yet recruiting
      • Tianjin Cancer Hospital
      • Contact: Zhanyu Pan, MD; Phone Number: 086-13820583299; Email: tjpanzhanyu@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: XY0206-12.5mg; Drug:XY0206;Dosage form:Tablet;Dosage：12.5mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.
EXPERIMENTAL: XY0206-25mg; Drug:XY0206;Dosage form:Tablet;Dosage：25mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.
EXPERIMENTAL: XY0206-37.5mg; Drug:XY0206;Dosage form:Tablet;Dosage：37.5mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.
EXPERIMENTAL: XY0206-50mg; Drug:XY0206;Dosage form:Tablet;Dosage：50mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.
EXPERIMENTAL: XY0206-75mg; Drug:XY0206;Dosage form:Tablet;Dosage：75mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.
EXPERIMENTAL: XY0206-100mg; Drug:XY0206;Dosage form:Tablet;Dosage：100mg;Include single dose treatment and multiple dose phase	Drug: XY0206; Dosage form:Tablet;Single dose treatment:Take the drug once on day 1,each time 1 tablet. Multiple dose phase:Take the medicine once a day,1 tablet at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until they meet the criteria for stopping treatment or determine the duration and interval of treatment according to the accumulated condition after multiple dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	The occurrence of DLT.	from the start of the medication to the end of the study or 28 days after cessation of medication
AE	The occurrence rate of AE.	from the start of the medication to the end of the study or 28 days after cessation of medication
ADR	The occurrence rate of adverse drug reactions(ADR).	from the start of the medication to the end of the study or 28 days after cessation of medication
SAE	The occurrence rate of SAE.	from the start of the medication to the end of the study or 28 days after cessation of medication
Blood routine	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
Urine routine	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
Stool routine	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
Blood biochemistry	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
Coagulation function	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
12 lead ecg	One of the laboratory tests.	from the start of the medication to the end of the study or 28 days after cessation of medication
Body temperature	One of the vital signs.	from the start of the medication to the end of the study or 28 days after cessation of medication
Blood pressure	One of the vital signs.	from the start of the medication to the end of the study or 28 days after cessation of medication
Heart rate	One of the vital signs.	from the start of the medication to the end of the study or 28 days after cessation of medication
Breathing	One of the vital signs.	from the start of the medication to the end of the study or 28 days after cessation of medication
General condition	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Skin	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Head	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Eyes	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Ears	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Nose	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Throat	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Heart	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Lung	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Chest	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Abdomen	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Limbs	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Nerves	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Back/spine	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication
Lymph nodes	One of the physical examination.	from the start of the medication to the end of the study or 28 days after cessation of medication

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf	area under the concentration-time curve from the time of dosing extrapolated to time infinity.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
AUC0-24h	area under the concentration-time curve from the time of dosing extrapolated to the 24h after dosing.	single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
AUC0-72h	area under the concentration-time curve from the time of dosing extrapolated to the 72h after dosing.	single dose phase:up to 72 hours
AUC0-120h	area under the concentration-time curve from the time of dosing extrapolated to the 120h after dosing.	single dose phase:up to 120 hours
Peak Plasma Concentration (Cmax)	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
CL/F	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Tmax	The amount of time that a drug is present at the maximum concentration in serum.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Cmin,ss	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Cmax,ss	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Cav,ss	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
PTF	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
RAUC1	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
RAUC2	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
RCmax	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Kel	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
t1/2	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Vz/F	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
AUC_%Extrap	The PK parameters of the plasma sample.	single dose phase:up to 120 hours;multiple dose phase:up to 24 hours
Ae0-24h	The PK parameters of the plasma sample.	single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
Fe0-24h	The PK parameters of the plasma sample.	single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
Ae0-72h	The PK parameters of the plasma sample.	single dose phase:up to 72 hours
Fe0-72h	The PK parameters of the plasma sample.	single dose phase:up to 72 hours
Ae0-72h stool	The PK parameters of the plasma sample.	single dose phase:up to 72 hours
CLr	The PK parameters of the plasma sample.	single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
Exploring the relative baseline change percentage of biomarkers (soluble VEGFR2).	The PD parameters of XY0206.	single dose phase:up to 24 hours;multiple dose phase:up to 24 hours
Complete response rate (CRR)	Effective parameters of XY0206.	through study completion,such as 30 months.
Partial response rate (PRR)	Effective parameters of XY0206.	through study completion,such as 30 months.
Objective response rate (ORR)	Effective parameters of XY0206.	through study completion,such as 30 months.
Progression-free survival (PFS)	Effective parameters of XY0206.	through study completion,such as 30 months.

Collaborators and Investigators

• Sponsor: Shijiazhuang Yiling Pharmaceutical Co. Ltd
• Collaborators: Tigermed Consulting Co., Ltd
• Investigators: Principal Investigator: Binghe Xu, MD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 19, 2018
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: August 8, 2018
• First Submitted That Met QC Criteria: August 31, 2018
• First Posted (ACTUAL): September 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 21, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: XY0206ONC1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No