Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

Bayer

Status and phase: Completed; Phase 1

Conditions: Neoplasms

Treatments: Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Cetuximab (ERBITUX)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01973868

16547

Details and patient eligibility

About

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)

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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42 participants in 1 patient group

Regorafenib

Experimental group

Description:

Regorafenib will be administered once daily on Days 1-21 of each 28-day Cycle (3 weeks on / 1 week off). The starting dose of regorafenib is 120 mg q.d., if this is tolerable in combination with cetuximab the dose will be escalated to 160 mg q.d.; if it is not tolerated the dose will be de-escalated to 80 mg q.d. Subjects will receive an initial i.v. infusion of cetuximab (loading dose of 400 mg/ m2 BSA) on Pre-cycle Day -7. The treatment of regorafenib in combination with cetuximab maintenance dose (250 mg/m2 BSA) starts on Cycle 1 Day 1. Cetuximab infusions will be given in a once-weekly dosing-regimen as approved.

Treatment:

Drug: Cetuximab (ERBITUX)

Drug: Regorafenib (Stivarga, BAY73-4506)