Clinical trial NCT01973868: Safety and Pharmacokinetics of Regorafenib and Cetuximab in Combination
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Regorafenib
Cetuximab
Solid tumors
Cancer
Safety
Tolerability
Pharmacokinetics
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-11-01
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) of regorafenib in combination with cetuximab
timeFrame: 1 month
measure: Number of participants with Adverse Events as a measure of safety and tolerability
timeFrame: Up to 2 years or longer
measure: Cmax,md (Cmax after multiple dose) for regorafenib and cetuximab
timeFrame: Multiple time points on Day 15
measure: AUC(0-24)md (AUC from time zero to 24 hours after multiple-dose administration) for regorafenib
timeFrame: Multiple time points on Day 15
measure: AUC(0-26)md (AUC from time zero to 26 hours after multiple-dose administration) for cetuximab
timeFrame: Multiple time points on Day 15
Secondary outcomes:
measure: Tumor response according to RECIST 1.1
timeFrame: Up to 2 years or longer
measure: tmax,md (tmax after multiple-dose administration) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
timeFrame: Multiple time points on Day 15
measure: tlast,md (tlast after multiple dosing) for regorafenib, its metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752) and cetuximab
timeFrame: Multiple time points on Day 15
measure: Cmax,md for metabolites M-2 (BAY75-7495) and M-5 (BAY81-8752)
timeFrame: Multiple time points on Day 15
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Health System
state: Pennsylvania
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.