Trial record 4 of 63 for:    "Nose Neoplasms"

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
  Purpose

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.


Condition Intervention Phase
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
Biological: cetuximab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 48
Study Start Date: October 2006
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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 ClinicalTrials.gov identifier: NCT00407810

Locations
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Athanassios Argiris University of Pittsburgh
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00407810     History of Changes
Other Study ID Numbers: NCI-2009-00171, 05-087, CDR0000515918, PCI-05-087, U01CA099168
Study First Received: December 4, 2006
Last Updated: July 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Nose Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Laryngeal Diseases
Tongue Neoplasms
Neoplasms, Unknown Primary
Laryngeal Neoplasms
Paranasal Sinus Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Otorhinolaryngologic Neoplasms
Respiratory Tract Neoplasms
Nose Diseases
Paranasal Sinus Diseases
Pharyngeal Neoplasms

ClinicalTrials.gov processed this record on August 19, 2014