Neoplasms
Conditions
Keywords
Phase I, Probe substrate, target therapy, small molecule, pharmacokinetics
Brief summary
* To evaluate the effect of BAY73-4506 on the pharmacokinetics of probe substrates of CYP 2C9 (warfarin), 2C19 (omeprazole) and 3A4 (midazolam) administered in a cocktail approach and on the pharmacokinetics of a probe substrate of CYP 2C8 (rosiglitazone) * To evaluate safety, anti-tumor activity, pharmacokinetics, and pharmacodynamics of BAY73-4506 in patients with advanced solid tumors
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
BAY73-4506 administered once a daily (od) in a 21-day on / 7-day off schedule
DRUGWarfarin
CYP 2C9 (warfarin) at Cycle 1
DRUGOmeprazole
CYP 2C19 (omeprazole) at Cycle 1
DRUGMidazolam
CYP 3A4 (midazolam) at Cycle 1
DRUGRosiglitazone
CYP2C8 (rosiglitazone) at Cycle 1
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female and male subjects must be ≥ 18 years at the first screening examination / visit * ECOG Performance Status of ≤ 2 * Histological or cytological documentation of confirmed advanced solid tumors. Subjects should have measurable or non-measurable disease according to RECIST * Life Expectancy of at least 3 months * Adequate bone marrow, liver, and renal functions as assessed by the following laboratory requirements conducted within 14 days prior to the first study treatment: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥1,500/mm3 * Platelet count ≥ 100,000/ mm3 * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) * Alkaline phosphatase ≤ 2 times ULN * ALT and AST ≤ 2.5 x ULN (≤ 5.0 x ULN for subjects with cancer involving the liver) * Serum creatinine ≤ 1.5 times ULN and glomerular filtration rate (GFR)≥ 30 ml/min/1.73 m2, according to the MDRD (Modified Diet in Renal Disease) abbreviated formula * Lipase ≤ 1.5 ULN * INR and PTT ≤ 1.5 ULN * Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants are not eligible for study participation in Group A. Subjects who are therapeutically treated with warfarin, heparin or other anticoagulants, will be allowed to participate in Group B of the study provided they meet all eligibility criteria. Close monitoring of at least weekly evaluations will be performed until INR or PTT are stable by the local standard of care. * Recovery from previous drug/procedure-related toxicities to CTC Grade 0 or 1 levels (except for alopecia), or to baseline preceding the prior treatment. Preexisting chemotherapy induced sensory neuropathy of CTC Grade ≤2 is not an
Exclusion criteria
. * Negative serum pregnancy test must be obtained within 7 days prior to the start of treatment in women of childbearing potential. Negative results must be available prior to study treatment. * Subjects enrolled in this study must use adequate barrier birth control measures prior to, during the course of the study, and 3 months after the last administration of regorafenib. * An adequate contraception includes the use of condoms or a vasectomy, hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy. In addition, adequate birth control measures for the subject's partner is required, such as a hormonal contraception with implants or combined PO contraceptives, certain intrauterine devices, bilateral tubal ligation, or hysterectomy, use of condoms or a vasectomy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics of probe substrates (AUC, Cmax, etc.) | Approximately 6 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Tumor Response evaluation measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) | Up to 3 years or longer if indicated |
| Adverse event collection | Up to 3 years or longer if indicated |
Countries
Canada
Outcome results
None listed