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

Tongue Cancer Clinical Trial

Official title:

A Phase II Trial of Cetuximab and Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00407810
• Other study ID #: NCI-2009-00171
• Secondary ID: 05-087CDR0000515
• Status: Completed
• Phase: Phase 2
• First received: December 4, 2006
• Last updated: July 26, 2013
• Start date: October 2006

Study information

• Verified date: July 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Laryngeal Neoplasms
• Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
• Nasopharyngeal Neoplasms
• Oropharyngeal Neoplasms
• Paranasal Sinus Neoplasms
• 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

Intervention

Biological:
• bevacizumab
Given IV
• cetuximab
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Michigan University Hospital	Ann Arbor	Michigan
United States	Case Western Reserve University	Cleveland	Ohio
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate with the combination of cetuximab and bevacizumab in recurrent or metastatic head and neck cancer	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.	Baseline and every 3 weeks if using physical exam or plain x-ray or every 6 weeks if using CT scan or MRI	No
Secondary	Overall survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab		Every 3 months for 2 years and then every 6 months for 3 years	No
Secondary	Progression-free survival of patients with recurrent or metastatic head and neck cancer treated with cetuximab plus bevacizumab		Every 2 months	No
Secondary	Rate of nonprogression (clinical response or stable disease)	Evaluated using RECIST criteria.	At 12 weeks	No
Secondary	Toxicity of cetuximab and bevacizumab in head and neck cancer patients.	Graded using the Common terminology Criteria for Adverse Events (CTCAE) version 4.0.	Evaluated on an ongoing basis	Yes
Secondary	Antitumor activity as measured by the level of biomarker in reverse phase protein arrays (RPPA)	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.	Baseline and day 21 of course 1	No