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Trial record 8 of 122 for:    regorafenib

Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Bayer Identifier:
First received: October 28, 2013
Last updated: October 4, 2016
Last verified: September 2016
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 Intervention Phase
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Cetuximab (ERBITUX)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Bayer:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 2 years or longer ] [ Designated as safety issue: Yes ]
  • Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab [ Time Frame: Multiple time points on Day 15 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response according to RECIST 1.1 [ Time Frame: Up to 2 years or longer ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) [ Time Frame: Multiple time points on Day 15 ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: November 2013
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01973868

United States, California
Los Angeles, California, United States, 90033
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Responsible Party: Bayer Identifier: NCT01973868     History of Changes
Other Study ID Numbers: 16547 
Study First Received: October 28, 2013
Last Updated: October 4, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Solid tumors

Additional relevant MeSH terms:
Antineoplastic Agents processed this record on October 27, 2016