Study of the Safety and Pharmacokinetics of BGB-283 in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT02610361
• Recruitment Status: Completed
• First Posted: November 20, 2015
• Last Update Posted: September 25, 2019
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: November 18, 2015
• First Posted Date: November 20, 2015
• Last Update Posted Date: September 25, 2019
• Actual Study Start Date: November 20, 2013
• Actual Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2018)

• Number of participants with adverse events in phase 1a [ Time Frame: From first dose to within 28 days of last dose of BGB-283, within 1 years in average ]
• Objective response rate based on RECIST Version 1.1 in subjects with selected tumor types in phase 1b [ Time Frame: From the first administration of the investigational product to the end of the study treatment, within 1 year in average ]

• Original Primary Outcome Measures (submitted: November 18, 2015): Number of participants with adverse events [ Time Frame: From first dose to within 28 days of last dose of BGB-283 ]
• Change History: Complete list of historical versions of study NCT02610361 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: July 22, 2018)

• Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast) in phase 1a [ Time Frame: During first 2 weeks ]
• Area under the plasma concentration-time curve from time 0 to infinity time in (AUC∞) in phase 1a [ Time Frame: During first 2 weeks ]
• Maximum plasma concentration (Cmax) in phase 1a [ Time Frame: During first 2 weeks ]
• Time to reach maximum plasma concentration (tmax) in phase 1a [ Time Frame: During first 2 weeks ]
• Terminal elimination half-life (t1/2) in phase 1a [ Time Frame: During first 2 weeks ]
• Tumor response in phase 1a [ Time Frame: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, within 1 year in average ]
• Number of participants with adverse events in phase 1b [ Time Frame: From first dose to within 28 days of last dose of BGB-283, within 1 year in average ]
• Progression-free survival (PFS) [ Time Frame: The interval from study treatment initiation until the determination of disease progression or death, within 1 year in average ]

Original Secondary Outcome Measures (submitted: November 18, 2015)

• Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast) [ Time Frame: During first 2 weeks ]
• Area under the plasma concentration-time curve from time 0 to infinity time (AUC∞) [ Time Frame: During first 2 weeks ]
• Maximum plasma concentration (Cmax) [ Time Frame: During first 2 weeks ]
• Time to reach maximum plasma concentration (tmax) [ Time Frame: During first 2 weeks ]
• Terminal elimination half-life (t1/2) [ Time Frame: During first 2 weeks ]
• Tumor response [ Time Frame: Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Safety and Pharmacokinetics of BGB-283 in Patients With Solid Tumors
• Official Title: A Phase 1A/1B, Open-Label, Multiple-Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Preliminary Antitumor Activities of the B RAF Inhibitor BGB 283 in Subjects With Solid Tumors
• Brief Summary: This study will evaluate the safety, tolerability, pharmacokinetic profile and treatment effect of a new drug known as BGB-283 in patients with solid tumours.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

Drug: BGB-283

In the dose escalation part(phase 1a): the dose levels will be escalated following a modified 3+3 dose escalation scheme.

In dose expansion phase(Phase 1b): Patients will be assigned to different groups based on their tumor types

Study Arms

Experimental: BGB-283

Intervention: Drug: BGB-283

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2016): 131
• Original Estimated Enrollment (submitted: November 18, 2015): 230
• Actual Study Completion Date: October 2017
• Actual Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Provided written informed consent prior to enrollment.
2. Male or female and at least 18 years of age.
3. A life expectancy of at least 12 weeks.
4. Histologically or cytologically confirmed advanced or metastatic solid tumor for which no effective standard therapy is available.
5. One of B-RAF, N-RAS, or K-RAS mutation positive solid tumor.
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 > 9 g/dL
   • Absolute neutrophil count ≥ 1000/mm^3
   • Platelets ≥ 100,000/mm^3
   • 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 ≥ 45 mL/min (calculated by the Cockcroft Gault formula).

9. Female subjects are eligible to enter and participate in the study if they are of:

   a) Non childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who

   i) Has had a hysterectomy,

   ii) Has had a bilateral oophorectomy (ovariectomy),

   iii) Has had a bilateral tubal ligation, or

   iv) Is post menopausal (total cessation of menses for ≥ 1 year).

   b) Childbearing potential, has a negative serum pregnancy test at screening (within 7 days of the first investigational product administration), and uses adequate contraception before study entry and throughout the study until 28 days after the last investigational product administration. Adequate contraception, when used consistently and in accordance with both the product label and the instructions of the physician, are defined as follows:

   i) Vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.

   ii) Any intrauterine device with a documented failure rate of less than 1% per year.

   iii) Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.

10. Subjects with treated brain metastasis are eligible to enter and participate in the study if they are neurologically stable.

Exclusion Criteria:

1. Female subjects who are pregnant or lactating.
2. Subjects receiving cancer therapy (chemotherapy or other systemic anti cancer therapies, immunotherapy, radiation therapy, or surgery) at the time of enrollment.
3. Any major surgery within 28 days prior to enrollment.
4. Any radiotherapy within 14 days prior to enrollment, providing the subject has recovered from all toxicities to NCI-CTCAE ≤ Grade 1.
5. Use of any investigational anti cancer drug within 28 days before the first investigational product administration.
6. Unresolved toxicity > Grade 1 (according to NCI-CTCAE, Version 4.03) from previous anti cancer therapy, unless agreed by the sponsor.
7. History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug or to any component of BGB-283. (To date there are no known Food and Drug Administration [FDA] approved drugs chemically related to BGB-283).
9. Untreated leptomeningeal or brain metastasis. Subjects with previously treated brain metastasis that are asymptomatic, off steroids for longer than 28 days are permitted.
10. Any unstable, pre-existing major medical condition that in the opinion of the Investigator contra indicates the use of an investigational product, including active infection, known human immunodeficiency virus (HIV) positive subjects, or known Hepatitis B or C.
11. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
12. As a result of the medical interview, physical examination or screening investigations, the investigator considers the subject unfit for study.
13. Is on medication listed in the protocol or requires any of these medications during treatment with BGB-283.
14. Candidates for curative therapy.
15. Unable or unwilling to comply with the required treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand

Administrative Information

• NCT Number: NCT02610361
• Other Study ID Numbers: BGB-283-AU-001; ACTRN12614001176651 ( Registry Identifier: The Australian New Zealand Clinical Trials Registry )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: BeiGene
• Study Sponsor: BeiGene
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: September 2019