Fluorouracil, Hydroxyurea, Cetuximab and Twice-daily Intensity Radiation Therapy for Advanced Head and Neck Cancer

Phase II Study of Concomitant Fluorouracil, Hydroxyurea, Cetuximab and Hyperfractionated Intensity Modulated Radiation Therapy for Locally Advanced Head and Neck Cancer

For advanced head and neck cancer, combined radiation and chemotherapy prevents recurrences and for many patients, improves survival. While combined cisplatin and radiation or cetuximab and radiation is more effective than radiation alone, approximately 50% of these patients will still recur. A more aggressive approach may be needed for these patients to prevent recurrence and death. The strategy of using multiple chemotherapy drugs with radiation given twice a day has been tested at Mount Sinai and University of Chicago. Approximately 80% of patients are cured with this strategy. While cure rates are higher than standard chemotherapy and radiation and the treatment is tolerable, side effects during treatment are common. We propose replacing a chemotherapy drug with a less toxic, targeted therapy called cetuximab. Our goal is to reduce toxicity while maintaining or improving cure rates for these patients.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Nose Neoplasms; Paranasal Sinus Neoplasms; Cancer of the Pharynx; Cancer of the Larynx; Cancer of the Oral Cavity
• Intervention / Treatment: Drug: Cetuximab; Drug: Hydroxyurea; Drug: Fluorouracil; Procedure: radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine

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:

• Age 18 years or older
• Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck or lymphoepithelioma
• No prior chemotherapy or radiotherapy
• Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor
• Karnofsky performance status of >= 70%
• Intact organ and bone marrow function
• Obtained informed consent

Exclusion Criteria:

• Demonstration of metastatic disease (i.e. M1 disease).
• Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea.
• Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years.
• Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment.
• Incomplete healing from previous surgery
• Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician.
• Uncontrolled active infection unless curable with treatment of their cancer.

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: Advanced Head and Neck Cancer; Patients with stage IVA and IVB or high-risk stage III squamous cell carcinomas of the head and neck

Drug: Cetuximab; 250 mg/m2 on Day 1 after the first dose of radiation was administered to all patients; Drug: Hydroxyurea; 500 mg orally every 12 hours with the morning dose administered 2 hours before radiation; Drug: Fluorouracil; continuous-infusion 5-FU at a dose of 600 mg/m2 daily for 120 hours; Procedure: radiotherapy; Radiotherapy was administered at 1.5 Gy per fraction twice daily with treatments separated by at least 6 hours on Days 1 through 5 on an alternating week schedule. Radiation was delivered with intensity-modulated radiation therapy (IMRT) planning for all patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Llocoregional Recurrence	Percentage of Participants with Loco-regional recurrence.	2 years
Survival	Overall Survival - Percentage of Participants who survived Disease-Free Survival - measured from the initiation of nonsurgical treatment to either the last follow-up, disease progression, or death using intent-to-treat methodology	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long- Term Toxicity	Grade 3 toxicities events	2 years
UW-QOLR: Quality of Life Score	University of Washington Quality of Life (UW-QOLR) questionnaire - covers 12 domains - pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood and anxiety. Each domain have between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response and reported as one composite score from 0 (worst) to 100 (best).	2 years
Distant Metastases	Percentage of participants who did not have distant control	2 years

Collaborators and Investigators

• Sponsor: Johnny Kao
• Investigators: Principal Investigator: Johnny Kao, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Kao J, Genden EM, Gupta V, Policarpio EL, Burri RJ, Rivera M, Gurudutt V, Som PM, Teng M, Packer SH. Phase 2 trial of concurrent 5-fluorouracil, hydroxyurea, cetuximab, and hyperfractionated intensity-modulated radiation therapy for locally advanced head and neck cancer. Cancer. 2011 Jan 15;117(2):318-26. doi: 10.1002/cncr.25374. Epub 2010 Sep 9.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: April 18, 2007
• First Submitted That Met QC Criteria: April 18, 2007
• First Posted (Estimate): April 19, 2007

Study Record Updates

• Last Update Posted (Actual): March 13, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Cancer of the Nasal Cavity
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Site; Musculoskeletal Diseases; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Bone Diseases; Paranasal Sinus Diseases; Nose Diseases; Laryngeal Diseases; Skull Neoplasms; Bone Neoplasms; Neoplasms; Head and Neck Neoplasms; Laryngeal Neoplasms; Pharyngeal Neoplasms; Paranasal Sinus Neoplasms; Nose Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Antisickling Agents; Fluorouracil; Hydroxyurea; Cetuximab
• Other Study ID Numbers: GCO 06-1155