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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00968435
First received: August 28, 2009
Last updated: October 8, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Other: bevacizumab, cisplatin, cetuximab, radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the 2-year progression-free survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine median overall survival for patients with locally or regionally advanced HNSCC treated with concurrent IMRT + cisplatin + bevacizumab + cetuximab. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of concurrent IMRT + cisplatin + bevacizumab + cetuximab. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To explore the potential utility of 18F FLT PET for early response assessment. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: August 2009
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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
  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: NCT00968435

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge
Basking Ridge, New Jersey, United States, 07939
United States, New York
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, United States, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, United States, 11570
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech
Investigators
Principal Investigator: Matthew Fury, MD, PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00968435     History of Changes
Other Study ID Numbers: 09-083
Study First Received: August 28, 2009
Last Updated: October 8, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
bevacizumab
cisplatin
cetuximab
radiation therapy
Phase II
09-083

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Bevacizumab
Cetuximab
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014