Cetuximab and Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00407810
First received: December 4, 2006
Last updated: July 26, 2013
Last verified: July 2013

December 4, 2006
July 26, 2013
October 2006
February 2012   (final data collection date for primary outcome measure)
Objective response rate with the combination of cetuximab and bevacizumab in recurrent or metastatic head and neck cancer [ Time Frame: Baseline and every 3 weeks if using physical exam or plain x-ray or every 6 weeks if using CT scan or MRI ] [ Designated as safety issue: No ]
Evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The 95% confidence intervals should be provided.
Objective response rate
Complete list of historical versions of study NCT00407810 on ClinicalTrials.gov Archive Site
  • Overall survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab [ Time Frame: Every 3 months for 2 years and then every 6 months for 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab [ Time Frame: Every 2 months ] [ Designated as safety issue: No ]
  • Rate of nonprogression (clinical response or stable disease) [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
    Evaluated using RECIST criteria.
  • Toxicity of cetuximab and bevacizumab in head and neck cancer patients. [ Time Frame: Evaluated on an ongoing basis ] [ Designated as safety issue: Yes ]
    Graded using the Common terminology Criteria for Adverse Events (CTCAE) version 4.0.
  • Antitumor activity as measured by the level of biomarker in reverse phase protein arrays (RPPA) [ Time Frame: Baseline and day 21 of course 1 ] [ Designated as safety issue: No ]
    The correlative study will evaluate the following biomarkers on tumor tissue using RPPA: EGFR, pEGFR, Src, pMAPK, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27, PARP, E-cadherin, p-ErbB3, Ki67, VEGF, and IL-8. In addition, we will examine EGFR gene copy number by FISH and serum EGFR. A 2-tailed Wilcoxon test at alpha = .01 will have 80% power to detect an increase or decrease of 0.9 for the "average" protein and 80% power to detect a difference of 1.8 in a protein with double the variability.
  • Overall survival
  • Progression-free survival
  • Twelve-week rate of nonprogression
  • Toxicity
Not Provided
Not Provided
 
Cetuximab and Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

This phase II trial is studying how well giving cetuximab together with bevacizumab works in treating patients with recurrent or metastatic head and neck cancer. Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab and bevacizumab may also stop the growth of head and neck cancer by blocking blood flow to the tumor. Giving cetuximab together with bevacizumab may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with cetuximab and bevacizumab.

SECONDARY OBJECTIVES:

I. Determine the progression-free and overall survival of patients treated with this regimen.

II. Determine the levels of soluble epidermal growth factor receptor (EGFR) in blood samples before and after dual EGFR and vascular endothelial growth factor inhibition.

III. Evaluate treatment-related toxicities of this regimen in these patients. IV. Collect and bank blood samples for future correlative studies.

OUTLINE: This is a multicenter study. Patients receive cetuximab intravenously (IV) over 1-2 hours on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tissue samples are collected at baseline to determine whether biomarkers on tumor tissue and/or blood can be linked with clinical response and to measure signaling pathways by reverse phase protein microarray. Epidermal growth factor receptor (EGFR) gene copy number is assessed by fluorescent in situ hybridization (FISH) on tumor tissue pretreatment. Blood samples are also collected at baseline and on day 21 of course 1 for analysis by acridinium-linked immunosorbent assay (ALISA) to quantify serum p110 sEGFR protein levels.

After completion of study treatment, patients are followed every 2-3 months for 2 years and then every 6 months for 3 years.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
  • Recurrent Metastatic Squamous Neck Cancer With Occult Primary
  • Recurrent Squamous Cell Carcinoma of the Hypopharynx
  • Recurrent Squamous Cell Carcinoma of the Larynx
  • Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Recurrent Squamous Cell Carcinoma of the Nasopharynx
  • Recurrent Squamous Cell Carcinoma of the Oropharynx
  • Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Stage IV Squamous Cell Carcinoma of the Hypopharynx
  • Stage IV Squamous Cell Carcinoma of the Larynx
  • Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
  • Stage IV Squamous Cell Carcinoma of the Nasopharynx
  • Stage IV Squamous Cell Carcinoma of the Oropharynx
  • Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
  • Tongue Cancer
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Biological: cetuximab
    Given IV
    Other Names:
    • C225
    • C225 monoclonal antibody
    • IMC-C225
    • MOAB C225
    • monoclonal antibody C225
  • Other: laboratory biomarker analysis
    Correlative studies
Experimental: Treatment (monoclonal antibody, antiangiogenesis therapy)
Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Biological: bevacizumab
  • Biological: cetuximab
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
Not Provided
February 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed squamous cell carcinoma of the head and neck

    • Metastatic and/or recurrent disease
  • Measurable disease defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by CT scan
  • Not eligible for curative-intent surgery or radiotherapy
  • No tumors invading major vessels (e.g., carotid artery) by imaging studies

    • No history of major, uncontrolled tumor-related bleeding despite locoregional treatment
    • Not at high-risk for recurrent tumor-related bleeding
  • No known brain metastases
  • ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 75,000/mm³
  • Bilirubin normal
  • AST and ALT ≤ 5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Urine protein: creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg by 24-hour urine collection
  • INR < 1.5
  • No history of gross hemoptysis (defined as bright red blood of ≥ ½ teaspoon) or coagulopathy
  • No history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis)
  • No history of severe infusion reaction to a monoclonal antibody
  • No CNS cerebrovascular ischemia or stroke within the past 6 months
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks
  • No significant traumatic injury within the past 4 weeks
  • No unstable angina or myocardial infarction within the past 6 months
  • No other malignancy within the past 3 years except curatively treated squamous cell or basal cell skin cancer or in situ cervical cancer
  • No uncontrolled illness including, but not limited to, any of the following:

    • Serious nonhealing wound, ulcer, or bone fracture
    • Symptomatic congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Clinically significant peripheral vascular disease
    • Active serious infection
    • Other coexisting medical or psychiatric condition that would preclude study compliance
  • No uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg) despite a stable regimen of antihypertensive therapy
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • At least 3 weeks since prior biologic/targeted agents
  • At least 3 weeks since prior radiotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • At least 4 weeks since prior major surgical procedure or open biopsy
  • At least 3 months since prior monoclonal antibody therapy
  • No prior cetuximab, bevacizumab, or other epidermal growth factor receptor or vascular endothelial growth factor-targeting agents
  • No more than 1 prior adjuvant or neoadjuvant chemotherapy or chemoradiotherapy regimen (may have included biologic therapy or a targeted agent)
  • No more than 1 prior treatment regimen (e.g, chemotherapy or biologic/targeted therapy) for recurrent or metastatic disease
  • No concurrent major surgery
  • No concurrent therapeutic anticoagulation except prophylactic warfarin 1 mg/day
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer agents or therapies
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00407810
NCI-2009-00171, 05-087, CDR0000515918, PCI-05-087, U01CA099168
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Athanassios Argiris University of Pittsburgh
National Cancer Institute (NCI)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP