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Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01973868
Recruitment Status : Completed
First Posted : November 1, 2013
Last Update Posted : April 9, 2019
Information provided by (Responsible Party):

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)

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Regorafenib (Stivarga, BAY73-4506) Drug: Cetuximab (ERBITUX) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 21, 2013
Actual Primary Completion Date : January 31, 2017
Actual Study Completion Date : April 3, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Regorafenib

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)

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab [ Time Frame: 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

  2. Number of participants with Adverse Events as a measure of safety and tolerability [ Time Frame: Up to 2 years or longer ]
  3. Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab [ Time Frame: Multiple time points on Day 15 ]
  4. AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib [ Time Frame: Multiple time points on Day 15 ]
  5. AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab [ Time Frame: Multiple time points on Day 15 ]

Secondary Outcome Measures :
  1. Tumor response according to RECIST 1.1 [ Time Frame: Up to 2 years or longer ]
  2. tmax,md (tmax after multiple-dose administration) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab [ Time Frame: Multiple time points on Day 15 ]
  3. tlast,md (tlast after multiple dosing) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab [ Time Frame: Multiple time points on Day 15 ]
  4. Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) [ Time Frame: Multiple time points on Day 15 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01973868

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United States, California
University of Southern California
Los Angeles, California, United States, 90033
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
University of Pittsburgh Medical Center Health System
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
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Study Director: Bayer Study Director Bayer
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Bayer Identifier: NCT01973868    
Other Study ID Numbers: 16547
First Posted: November 1, 2013    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Solid tumors
Additional relevant MeSH terms:
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Antineoplastic Agents, Immunological
Antineoplastic Agents