Clinical trial NCT03453034: Tolerance and Pharmacokinetics of TQ-B3233
Official title: To Study the Pharmacokinetic Characteristics of TQ-B233 in the Human Body, Recommend a Reasonable Regimen for Subsequent Research
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Tumor
Keywords: TQ-B3233
tumor
toleration
pharmacokinetics
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Study of Tolerance and Pharmacokinetics of TQ-B3233 Capsule, phase I,single arm.

Detailed description: The maximum tolerated dose (MTD) of TQ-B3233 \[ Time Frame: 48 weeks \] \[ Designated as safety issue: Yes \]The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment.

Pharmacokinetics of TQ-B3233 (in whole blood):In the study of single-dose, full PK profiles will be obtained at H0/H0.5/H1/H2/H3/H5/H8/H10/H12/H24/H48/H72（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D0/D1/D2/D8/D15/D22/D28（D means Day）.

Eligibility criteria: Inclusion Criteria:

* Patients definitely diagnosed by pathology and/or cytology as BRAF mutation advanced malignant melanoma.
* 18-70 years old, ECOG PS:0-1,Life expectancy of more than 3 months;
* Patients treated with chemotherapy agents or surgery before being enrolled into the study need waiting for 4 weeks, 6 weeks will be needed if agents were nitrocarbamide and mitomycin C;
* Main organs function is normal;
* Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped;
* Patients should be voluntary and sign the informed consent before taking part in the study;

Exclusion Criteria:

* Patients with Malignant tumors within 5 years, except for non-melanoma skin cancer and in situ cancer;
* Patients who had previously received specific BRAF inhibitors;
* A variety of factors that affect oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.)
* Patients who participated in other anticancer drug clinical trials within 4 weeks ;
* Blood pressure unable to be controlled ideally by one drug(systolic pressure≥150 mmHg，diastolic pressure≥90 mmHg);
* Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias or cardiac insufficiency (including QTc≥480ms) and patients with Grade 3 or higher congestive heart failure (NYHA Classification);
* Patients with non-healing wounds or fractures;
* Patients with brain metastasis, spinal cord compression, cancerous meningitis, CT or MRI examination reminds patients with cerebral or soft meningeal diseases in the screening phase;
* Patients with drug abuse history or unable to get rid of drugs or Patients with mental disorders;
* Coagulation function abnormality: haemorrhagic tendencies (e.g. active digestive tract ulcer), or are receiving thrombolytic or anticoagulant therapy;
* Patients with immunodeficiency, including HIV positive or other acquired, congenital immunodeficiency disease, or organ transplant history;
* Patients with thyroid dysfunction;
* Patients with concomitant diseases which could seriously endanger themselves or those who won't complete the study according to investigators;
* Parents with hepatitis b surface antigen positive or HCV;

Primary outcomes:
measure: maximum tolerated dose(MTD)
timeFrame: 28 Days
measure: dose-limiting toxicity(DLT)
timeFrame: 28 Days
measure: Peak Plasma Concentration(Cmax)
timeFrame: up to 28 Days
measure: Peak time(Tmax)
timeFrame: up to 28 Days
measure: Half life(t1/2)
timeFrame: up to 28 Days
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: up to 28 Days
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing cancer hospital
Study officials:
References: