None listed
Conditions
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. Who is it for? You may be eligible to join this study if you are aged 18 years or above, and have a confirmed diagnosis of advanced or metastatic solid tumour for which no effective standard therapy is available. Study details All participants in this study will receive treatment with a new drug known as BGB-283. Treatment will be administered by oral capsule [once daily for 24 days (Cycle 1 only) and 21 days (Cycle 2 onwards) each cycle]. Initially a low dose will be administered to participants. If this dose is tolerated, then it will be increased in the next group of patients and so on until the maximum tolerated dose is determined. All participants will be regularly monitored for safety and tolerability of the medication for about 1 year. They will also be required to give blood samples (on days when frequent pharmacokinetic sampling is required), FDG-PET scan (screening and the first day of Cycle 2) and CT scans (screening and subsequent every 6 weeks) during the study. This will provide us with supportive data for further development of this medication.
Interventions
This is a multicenter, Phase I, open label, multiple dose, dose escalation, first in human study of the B-RAF inhibitor BGB-283.
The dose levels will be escalated throughout the study up to the MTD or the predicted efficacy level. Dose escalation will follow a standard 3+3 dose escalation design (detail is described as below).
Cohort 1: 5 mg oral capsule once daily
Cohort 2: 10 mg oral capsule once daily
Cohort 3: 20 mg oral capsule once daily
Cohort 4: 30 mg oral capsule once daily
Cohort
This is a multicenter, Phase I, open label, multiple dose, dose escalation, first in human study of the B-RAF inhibitor BGB-283. The dose levels will be escalated throughout the study up to the MTD or the predicted efficacy level. Dose escalation will follow a standard 3+3 dose escalation design (detail is described as below). Cohort 1: 5 mg oral capsule once daily Cohort 2: 10 mg oral capsule once daily Cohort 3: 20 mg oral capsule once daily Cohort 4: 30 mg oral capsule once daily Cohort 5: 40 mg oral capsule once daily Cohort 6: 60 mg oral capsule once daily The starting dose will be 5 mg/day (5 mg once daily). The 24 day initial treatment cycle (Cycle 1) of each dose will consist of a single administration of BGB-283 (Day 1), followed by a 2 day treatment free period (Days 2 and 3) and a 21 day period of repeated drug administration (Days 4 to 24). Evaluation of a cohort of at least three (3) subjects completing one cycle of treatment at that dose level is required prior to determining the next dose level and dose regimen for the next cohort. If a subject wishes to continue study treatment on completion of Cycle 1, the subject can continue study treatment in 21 day Cycle 2 (with no treatment free or rest period) and subsequent cycles (same as Cycle 2, all of 21 days' duration), at the discretion of the investigator. The continuous safety evaluation will be performed by the sponsor, the coordinating investigator, and investigators. A Safety Monitoring Committee (SMC) will be established for the determination of dose levels to be administered and dose regimen during dose escalation, and will depend on the data available from the previous dose levels. The investigator is responsible for investigational product accountability, reconciliation, and record maintenance. In accordance with all applicable regulatory requirements, the investigator or designated study center personnel must maintain investigational product accountability records throughout the course of the study. This person(s) will document the amount of investigational product received from the sponsor, the amount supplied and/or administered to and returned by subjects, if applicable. After completion of the study, all unused BGB-283 will be inventoried and packaged for return shipment by the hospital unit pharmacist. The inventoried supplies will be returned to the sponsor or destroyed on site, after receiving written sponsor approval.
Sponsors
BeiGene Aus Pty Ltd
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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: i) Absolute neutrophil count >=1000/mm3 ii) Platelets >=100,000/mm3 iii) Total bilirubin <=1.5 times the upper limit of normal (ULN) iv) Aspartate aminotransferase and alanine aminotransferase <=2.5 x ULN (<=5 x ULN for subjects with known liver metastasis) v) 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 paticipate 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. Have received prior systemic anti cancer treatment within the following time frames: i) Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g,. 6 weeks for nitrosourea, mitomycin C) prior to starting study treatment ii) Biologic therapy (e.g,. antibodies), continuous or intermittent small molecule therapies, or any other investigational agents within a period of five times the half life of the agent or <=4 weeks (whichever is shorter) prior to starting study treatment 4. Any major surgery within 28 days prior to enrollment. 5. Any radiotherapy within 14 days prior to enrollment, providing the subject has recovered from all toxicities to NCI-CTCAE <=Grade 1. 6. Use of any investigational anti cancer drug within 28 days before the first investigational product administration. 7. Unresolved toxicity >Grade 1 (according to NCI-CTCAE, Version 4.03) from previous anti cancer therapy, unless agreed by the sponsor. 8. History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs. 9. 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). 10. Untreated leptomeningeal or brain metastasis. Subjects with previously treated brain metastasis that are asymptomatic, off steroids and anti seizure medications for longer than 28 days are permitted. 11. 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. 12. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 13. As a result of the medical interview, physical examination or screening investigations, the investigator considers the subject unfit for study. 14. Is on medication listed in the protocol or requires any of these medications during treatment with BGB-283. 15. Candidates for curative therapy. 16. Unable or unwilling to comply with the required treatment.
Outcome results
None listed