Clinical trial NCT03641586: The Study of BGB-283 in Chinese Subjects With Local Advanced or Metastatic Malignant Solid Tumor
Official title: A Phase I, Single and Multiple Dose Escalation/Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Food Effect, and Preliminary Antitumor Activities of BGB-283 in Chinese Subjects With Local Advanced or Metastatic Malignant Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Dose Escalation
Dose Expansion
BGB-283
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2018-08-22
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety, tolerability, pharmacokinetics, food effect, and preliminary antitumor activities of BGB-283 in Chinese subjects with local advanced or metastatic malignant solid tumor.

Detailed description: "This study is conducted on the basis of the completed multi-dose, dose escalation, Phase IA trial in Australia, is a dose-finding, dose expansion and food effects study of BGB-283 capsules in Chinese patients with locally advanced or metastatic solid tumor to determine the tolerability, safety, pharmacokinetic profiles, preliminary efficacy, food effects under high-fat meal on the absorption and metabolism of BGB-283, and preliminary anti-tumor efficacy.

The study was conducted in three phases: Stage I for dose escalation, Stage II for dose expansion and Stage III for food effects on pharmacokinetics under high fat meal.

Stage I Dose escalation: In a open-label, dose-escalation design, dose escalation will be performed with the '3 + 3' scheme and the dosage levels of BGB-283 capsules will be gradually increased.

Stage II Dose expansion: 20 mg/qd and 30 mg/qd are considered as effective and safe doses, based on preliminary results from Phase IA clinical studies in Australia. To further understand the preliminary pharmacodynamic results of BGB-283 in Chinese patients with malignant melanoma, 20mg/qd dose expansion study in B-RAF mutated malignant melanoma will be further explored if it has been proved to be a safe dose in Chinese population according to the '3 + 3' scheme.

Stage III uses multi-center, open, two-group crossover self-control design to compare the high-fat meal effect on pharmacokinetics."

Eligibility criteria: Inclusion Criteria:

1. Provided written informed consent prior to enrollment.
2. Male or female and between 18 and 75 years old.
3. A life expectancy of more than 12 weeks.
4. Stage I and III: Histologically or cytologically confirmed advanced or metastatic solid tumor for which no effective standard therapy is available. We simultaneously require patients with one of B-RAF, N-RAS, or K-RAS mutation positive solid tumor.
5. In Stage II: we require advanced or metastatic melanoma with the B-RAF mutation.
6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
7. Able to swallow and retain oral medication.
8. Adequate bone marrow, liver, and renal function:

   * Hemoglobin \> 90 g/L
   * Absolute neutrophil count ≥ 1.5x10\^9/L
   * Platelets ≥ 100 x10\^9/L
   * Total bilirubin ≤1.5 times the upper limit of normal (ULN)
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with known liver metastasis)
   * Creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft Gault formula).

Exclusion Criteria:

1. Female subjects who are pregnant or lactating.
2. Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies used to control cancer must have been completed at least 4 weeks or at least 5 half-lives (whichever is shorter before study drug administration, but at least 21 days)
3. Any major surgery within 28 days prior to enrollment.
4. Any radiotherapy for metastatic foci within 14 days prior to enrollment,
5. Unresolved toxicity \> Grade 1 (according to NCI-CTCAE, Version 4.03) from previous anti cancer therapy.
6. History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
7. Any clinical significant active infection that need systematic treatment, including HIV positive subjects, or known Hepatitis B or C.

Primary outcomes:
measure: Stage 1: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average
timeFrame: From signing the informed consent form and throughout the study, 1 year in average
measure: Stage 2: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1
timeFrame: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average
measure: Stage 3: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)
timeFrame: Within 43 days since first dose
measure: Stage 3: Maximum plasma concentration (Cmax)
timeFrame: Within 43 days since first dose
measure: Stage 3: Terminal elimination half-life (t1/2)
timeFrame: Within 43 days since first dose
measure: Stage 3: Detect Ka for Pop-PK analysis
timeFrame: Within 43 days since first dose
measure: Stage 3: Detect CL/F for Pop-PK analysis
timeFrame: Within 43 days since first dose
measure: Stage 3: Detect Vc/F for Pop-PK analysis
timeFrame: Within 43 days since first dose
Secondary outcomes:
measure: Stage 1: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)
timeFrame: Within 43 days since first dose
measure: Stage 1: Maximum plasma concentration (Cmax)
timeFrame: Within 43 days since first dose
measure: Stage 1: Terminal elimination half-life (t1/2)
timeFrame: Within 43 days since first dose
measure: Stage 1: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1
timeFrame: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average
measure: Stage 2: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average
timeFrame: From signing the informed consent form and throughout the study, 1 year in average
measure: Stage 3: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1
timeFrame: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, 1 year in average
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: BeiGene
name: Xiang Li, MD
role: STUDY_DIRECTOR
References: