Neoplasms
Conditions
Keywords
Regorafenib, Cetuximab, Solid tumors, Cancer, Safety, Tolerability, Pharmacokinetics
Brief summary
To establish safety, tolerability and pharmacokinetics of regorafenib and cetuximab in combination, and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
Interventions
DRUGRegorafenib (Stivarga, BAY73-4506)
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors who are not candidates for standard therapy or in whom regorafenib or cetuximab is considered a standard treatment. Patients with metastatic colorectal cancer (mCRC) must have a record of K-ras gene mutational analysis available and no K-ras mutation is present. * Male or female patients ≥ 18 years of age * Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment * Life expectancy of at least 3 months * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days of starting the study treatment: * Platelet count ≥ 100,000/cubic millimeters (mm3), hemoglobin (Hb) ≥ 8.5 g/dl, leukocyte count \> 3,000/mm3, absolute neutrophil count (ANC) ≥ 1,000/mm3 * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Mildly elevated total bilirubin (\< 6 mg/dL) is allowed if Gilbert's syndrome is documented. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) * Alkaline phosphatase limit ≤ 2.5 x ULN (≤ 5 x ULN for subjects whose cancer involves their liver). * Amylase and lipase ≤ 1.5 x ULN * Serum creatinine ≤ 1.5 times ULN and creatinine clearance (CLcr) ≥ 30 mL/min according to the Cockroft-Gault formula * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Exclusion criteria
* Prior treatment with Regorafenib * Prior discontinuation of cetuximab treatment due to toxicity or intolerance of cetuximab * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication * Non-healing wound, ulcer, or bone fracture * Systemic anticancer therapy within 28 days * Patients unable to swallow and retain oral medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab | Multiple time points on Day 15 | — |
| Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab | 1 month | MTD is defined as the maximum dose at which the incidence of dose-limiting toxicities (DLTs) during Cycle 1 is below 20 %, or as the maximum dose administered, whichever is achieved first during dose escalation |
| Number of participants with Adverse Events as a measure of safety and tolerability | Up to 2 years or longer | — |
| Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab | Multiple time points on Day 15 | — |
| AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib | Multiple time points on Day 15 | — |
Secondary
| Measure | Time frame |
|---|---|
| tmax,md (tmax after multiple-dose administration) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab | Multiple time points on Day 15 |
| tlast,md (tlast after multiple dosing) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab | Multiple time points on Day 15 |
| Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) | Multiple time points on Day 15 |
| Tumor response according to RECIST 1.1 | Up to 2 years or longer |
Countries
United States
Outcome results
None listed