Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

NCT01973868 | Completed Phase 1 FDA Drug

• 1 other identifier: 16547
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 4

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)

Conditions

Neoplasms

Keywords

Regorafenib; Cetuximab; Solid tumors; Cancer; Safety; Tolerability; Pharmacokinetics

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab

  Multiple time points on Day 15

Secondary Outcomes (4)

• Tumor response according to RECIST 1.1

  Up to 2 years or longer

• 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

Study Arms (1)

Regorafenib

EXPERIMENTAL

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.

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

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

Regorafenib

Cetuximab (ERBITUX) DRUG

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (4)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Medical Center Health System

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Publications (1)

• Weekes C, Lockhart AC, Lee JJ, Sturm I, Cleton A, Huang F, Lenz HJ. A phase 1b study evaluating the safety and pharmacokinetics of regorafenib in combination with cetuximab in patients with advanced solid tumors. Int J Cancer. 2019 Nov 1;145(9):2450-2458. doi: 10.1002/ijc.32317. Epub 2019 Jun 14.

  PMID: 30958892 DERIVED

Related Links

• Click here to find results for studies related to Bayer products.

MeSH Terms

Conditions

Neoplasms

Interventions

regorafenib; Cetuximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2013
• First Posted: November 1, 2013
• Study Start: November 21, 2013
• Primary Completion: January 31, 2017
• Study Completion: April 3, 2018
• Last Updated: April 9, 2019

Record last verified: 2019-04

Locations

US (4)