Bevacizumab, Cetuximab, and Cisplatin With IMRT (Intensity-Modulated Radiation Therapy) for Patients With Stage III/IV Head and Neck Squamous Cell Carcinoma

Phase II Trial of Bevacizumab, Cetuximab, and Cisplatin With IMRT (Intensity-Modulated Radiation Therapy) for Patients With Stage III/IV Head and Neck Squamous Cell Carcinoma

The purpose of this study is to determine the effectiveness of treatment with bevacizumab + cisplatin + cetuximab + IMRT. The doctor wishes to monitor patients for 2 years after the completion of study treatment to determine if they are cancer-free during that time. They also want to evaluate the side effects that patients experience with this treatment regimen.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Other: bevacizumab, cisplatin, cetuximab, radiation therapy

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07939
      • Memorial Sloan Kettering Cancer Center at Basking Ridge
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center at Commack
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rockville Centre, New York, United States, 11570
      • Memorial Sloan Kettering Cancer Center at Mercy Medical Center
    • Sleepy Hollow, New York, United States, 10591
      • Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stage III/IV HNSCC without distant metastasis. Patients with stage II squamous cell carcinoma of the hypopharynx will also be eligible
• Adequate renal function, with serum creatinine ≤ 1.5 mg/dL. Patients with serum creatinine > 1.5 mg/dL may be eligible if calculated creatinine clearance > or = to 55 ml/min by Cockcroft and Gault equation (or 24-hour urine collection).
• Age > or = to 18 years.
• Karnofsky performance status > or = to 70%
• Adequate bone marrow function: absolute neutrophil count > or = to 1,500/ platelets > or = to 100,000/ul, hemoglobin > or = to 9 gm/dl
• Adequate hepatic function: Total bilirubin ≤ 1.5 X ULN (patients with Gilbert's syndrome as the cause of hyperbilirubinemia may be eligible if total bilirubin ≤ 2.5 X ULN), aspartate aminotransferase (AST) ≤ 2.5 X ULN, alanine aminotransferase (ALT) ≤ 2.5 X ULN, alkaline phosphatase ≤ 2.5 X ULN.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Patients must have ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior radiation therapy for HNSCC
• Prior treatment of HNSCC with bevacizumab or other agents specifically targeting VEGF
• Prior treatment of HNSCC with cetuximab or other agents specifically targeting EGFR
• Other active malignancy, other than indolent malignancies, which the investigator determines are unlikely to interfere with treatment or efficacy analysis. For example, patients with non-melanoma skin cancer, in situ carcinoma of the cervix, or prostate cancer within the no current biochemical (PSA) or radiologic evidence of disease may enroll.
• Patients with nasopharyngeal carcinoma
• Patients who will receive amifostine as part of the radiation treatment plan
• Patients with skin breakdown/ulceration (CTCAE version 3.0, grade 2 or higher).
• Patients with hearing loss requiring hearing aid or intervention (i.e. interfering in a clinically significant way with activities of daily living).
• Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living).
• Any prior documented history of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
• History of unstable angina or myocardial infarction (MI) within the last year.
• Urine protein: creatinine (UPC) ratio > or = to 1.0 at screening. A random urine sample is collected. Total protein (mg/dL) and spot creatinine (mg/dL) are ordered for this sample. The UPC ratio is calculated from the results of these tests.
• International normalized ratio (INR) > 1.5 or activated partial thromboplastin time (aPTT) > 1.5 X upper limits of normal (ULN)
• Current use of warfarin, current use of heparin or low-molecular weight heparin, chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function.
• Patients with gross hemoptysis or hematemesis (defined as bright red blood of 1 teaspoon of more) within 28 days prior to Day 0 protocol treatment will be excluded from this trial. Patients with incidental blood mixed with phlegm are not excluded.
• Esophageal varices, non-healing ulcer, wound, or bone fracture are exclusion criteria. However, patients with skin breakdown overlying malignant neck lymphadenopathy may be eligible, at the discretion of the investigator.
• Anatomic lesion that increases the risk of serious hemorrhage, such as encasement or invasion of major blood vessels by primary tumor and/or by involved lymph nodes
• Blood pressure of > 150/100 mmHg
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• Clinically significant peripheral vascular disease
• History of bleeding diathesis or hemorrhagic disorder, or coagulopathy.
• Major surgical procedure or significant traumatic injury within 28 days prior to treatment with bevacizumab
• Core biopsy within 7 days prior to treatment with bevacizumab.
• Minor surgical procedures such as fine needle aspirations or placement of percutaneous gastrostomy tube (PEG) less than 7 days prior to treatment with bevacizumab
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior enrollment.
• Inability to comply with study and/or follow-up procedures
• Women who are pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: (IMRT) + cisplatin + bevacizumab + cetuximab; This is a single-institution, non-randomized, phase II study. The primary endpoint is to determine 2-year progression-free survival for patients with locally or regionally advanced HNSCC treated with concurrent intensity modulated radiation therapy (IMRT) + cisplatin + bevacizumab + cetuximab.

Other: bevacizumab, cisplatin, cetuximab, radiation therapy; Patients will receive intensity-modulated radiation therapy (IMRT) in once-daily fractions. A total dose of 70Gy is planned for the primary tumor site over approximately 33 treatment days. Day 1 will refer to the first day of radiation therapy. Concurrent with radiation therapy, patients will receive cisplatin (50 mg/m2 IV on Days 1, 2 and 22, 23) and bevacizumab (15 mg/kg IV on Days 1 and 22). Cetuximab will be administered according to the Bonner regimen (4),with a loading dose approximately 7 days prior to the start of radiation therapy (400 mg/m2 IV once, on approximately Day minus 7), followed by weekly cetuximab infusions (250 mg/m2 IV weekly X 7 infusions) until the completion of radiation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the 2-year progression-free survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine median overall survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab.	2 years
To evaluate the safety and tolerability of concurrent IMRT + cisplatin + bevacizumab + cetuximab.	2 years
To explore the potential utility of 18F FLT PET for early response assessment.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Genentech, Inc.

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: August 28, 2009
• First Submitted That Met QC Criteria: August 28, 2009
• First Posted (Estimate): August 31, 2009

Study Record Updates

• Last Update Posted (Estimate): August 10, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: cisplatin; bevacizumab; radiation therapy; Phase II; cetuximab; 09-083
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Cetuximab
• Other Study ID Numbers: 09-083