The Study of BGB-283 in Chinese Subjects With Local Advanced or Metastatic Malignant Solid Tumor

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03641586
• Other study ID #: BGB-283-CN-001
• Secondary ID: CTR20150575
• Status: Completed
• Phase: Phase 1
• Start date: October 12, 2015
• Est. completion date: March 7, 2019

Study information

• Verified date: May 2019
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 7, 2019
• Est. primary completion date: December 6, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• BGB-283

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Beijing Cancer Hosptial	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stage 1: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average		From signing the informed consent form and throughout the study, 1 year in average
Primary	Stage 2: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1		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
Primary	Stage 3: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)		Within 43 days since first dose
Primary	Stage 3: Maximum plasma concentration (Cmax)		Within 43 days since first dose
Primary	Stage 3: Terminal elimination half-life (t1/2)		Within 43 days since first dose
Primary	Stage 3: Detect Ka for Pop-PK analysis		Within 43 days since first dose
Primary	Stage 3: Detect CL/F for Pop-PK analysis		Within 43 days since first dose
Primary	Stage 3: Detect Vc/F for Pop-PK analysis		Within 43 days since first dose
Secondary	Stage 1: Area under the plasma concentration-time curve from time 0 to infinity time (AUC)		Within 43 days since first dose
Secondary	Stage 1: Maximum plasma concentration (Cmax)		Within 43 days since first dose
Secondary	Stage 1: Terminal elimination half-life (t1/2)		Within 43 days since first dose
Secondary	Stage 1: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1		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
Secondary	Stage 2: Number of participants with treatment-related adverse events as assessed by CTC AE 4.03, 1 year in average		From signing the informed consent form and throughout the study, 1 year in average
Secondary	Stage 3: To determine the objective response rate (ORR) as assessed by RECIST, Version 1.1		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