Clinical trial NCT02610361: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of participants with adverse events in phase 1a
timeFrame: From first dose to within 28 days of last dose of BGB-283, within 1 years in average
measure: Objective response rate based on RECIST Version 1.1 in subjects with selected tumor types in phase 1b
timeFrame: From the first administration of the investigational product to the end of the study treatment, within 1 year in average
Secondary outcomes:
measure: Area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUClast) in phase 1a
timeFrame: During first 2 weeks
measure: Area under the plasma concentration-time curve from time 0 to infinity time in (AUC∞) in phase 1a
timeFrame: During first 2 weeks
measure: Maximum plasma concentration (Cmax) in phase 1a
timeFrame: During first 2 weeks
measure: Time to reach maximum plasma concentration (tmax) in phase 1a
timeFrame: During first 2 weeks
measure: Terminal elimination half-life (t1/2) in phase 1a
timeFrame: During first 2 weeks
measure: Tumor response in phase 1a
timeFrame: 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
measure: Number of participants with adverse events in phase 1b
timeFrame: From first dose to within 28 days of last dose of BGB-283, within 1 year in average
measure: Progression-free survival (PFS)
timeFrame: The interval from study treatment initiation until the determination of disease progression or death, within 1 year in average
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Chris Obrien Lifehouse
state: New South Wales
city: Macquarie
country: Australia
facility: North Coast Cancer Institute
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Southport Gold Coast
country: Australia
facility: Tasman Oncology Research Ltd
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Cancer Trials
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton Waikato
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital (Ccdhb)
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Jayesh Desai, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desai J, Gan H, Barrow C, Jameson M, Atkinson V, Haydon A, Millward M, Begbie S, Brown M, Markman B, Patterson W, Hill A, Horvath L, Nagrial A, Richardson G, Jackson C, Friedlander M, Parente P, Tran B, Wang L, Chen Y, Tang Z, Huang W, Wu J, Zeng D, Luo L, Solomon B. Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. J Clin Oncol. 2020 Jul 1;38(19):2140-2150. doi: 10.1200/JCO.19.02654. Epub 2020 Mar 17.