Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

Neoplasms Clinical Trial

Official title:

A Phase 1b, Multi-center, Non-randomized, Open Label, Dose Escalation Design Study of Regorafenib (BAY73-4506) in Combination With Cetuximab in Subjects With Locally Advanced or Metastatic Solid Tumors Who Are Not Candidates for Standard Therapy or in Whom Regorafenib or Cetuximab is Considered as a Standard Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01973868
• Other study ID #: 16547
• Status: Completed
• Phase: Phase 1
• Start date: November 21, 2013
• Est. completion date: April 3, 2018

Study information

• Verified date: April 2019
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: April 3, 2018
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Regorafenib (Stivarga, BAY73-4506)

• Cetuximab (ERBITUX)

Locations

Country	Name	City	State
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Southern California	Los Angeles	California
United States	University of Pittsburgh Medical Center Health System	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab	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	1 month
Primary	Number of participants with Adverse Events as a measure of safety and tolerability		Up to 2 years or longer
Primary	Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab		Multiple time points on Day 15
Primary	AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib		Multiple time points on Day 15
Primary	AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab		Multiple time points on Day 15
Secondary	Tumor response according to RECIST 1.1		Up to 2 years or longer
Secondary	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
Secondary	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
Secondary	Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752)		Multiple time points on Day 15

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