INDUCTION CHEMOTHERAPY FOLLOWED BY CETUXIMAB AND RADIATION THERAPY FOR HEAD AND NECK CANCER (DREXNECK)

This study is currently recruiting participants.
Verified February 2013 by Drexel University
Sponsor:
Information provided by (Responsible Party):
Drexel University
ClinicalTrials.gov Identifier:
NCT01467115
First received: November 4, 2011
Last updated: February 20, 2013
Last verified: February 2013
  Purpose

More than 50% of Head and Neck cancers are locally advanced at presentation. Although surgery, in combination with other modalities like radiation therapy can achieve 40-50% five year survival rates, resection in the head and neck region can leave patients with poor functional and cosmetic outcomes.

Due to these concerns about quality of life after surgery, there has been a lot of interest in non surgical alternatives of treatment. Various combinations of radiation, chemotherapy and biologics has showed promising results. However, questions still remain about the ideal combination treatment regimen.

Based on assimilation of data from multiple sources, our study tries to identify the role of a potentially highly effective multi-modality regimen based on induction chemotherapy (Cisplatin, Docetaxel and 5 Fluorouracil) followed by combination of a biologic agent, Cetuximab, and radiation therapy.


Condition Intervention Phase
Head and Neck Cancer
Radiation: Radiotherapy
Drug: Leucovorin
Biological: Cetuximab
Drug: Filgrastim
Drug: Erythropoetin
Drug: Cisplatin
Drug: Fluorouracil
Drug: Docetaxel
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: INDUCTION CHEMOTHERAPY WITH DOCETAXEL, CISPLATIN, AND 5-FLUOROURACIL FOLLOWED BY CONCOMITANT CETUXIMAB AND RADIATION THERAPY FOR LOCOREGIONALLY ADVANCED SQUAMOUS CELL CANCER OF THE HEAD AND NECK: A PHASE II TRIAL

Resource links provided by NLM:


Further study details as provided by Drexel University:

Primary Outcome Measures:
  • Organ Sparing Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    to determine whether the intervention will prolong survival without needing salvage surgery (organ sparing survival)


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    we will determine if the intervention prolongs overall survival.


Estimated Enrollment: 25
Study Start Date: March 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Treatment with induction chemotherapy followed by radiation and cetuximab.
Radiation: Radiotherapy
3D conformal radiation therapy or Intensity-Modulated Radiation Therapy (IMRT) with or without Image Guided Radiation Therapy (IGRT) will be used for all patients. Radiotherapy will be delivered in 1.8 to 2.25 Gy fractions daily, five days per week excluding holidays, for a total of 66-72 Gy delivered to the Gross Tumor Volume (GTV, defined below) plus appropriate margin and 44-59.4 Gy to at-risk lymph nodes as determined by primary tumor characteristics. Alternative fractionation and dosing schema may be used as deemed appropriate for an individual case. For IMRT, the minimum Planning Target Volume (PTV) dose should be 90% of the prescription dose and a minimum of 95% of the PTV should receive the prescribed dose.
Other Names:
  • 3D conformal radiation therapy
  • Intensity-Modulated Radiation Therapy (IMRT)
Drug: Leucovorin
5FU is given after, or at the midpoint, of the leucovorin infusion. Leucovorin is usually administered by I.V. bolus injection or short (10-120 minutes) I.V. infusion but oral formulation may be substituted should supply warrant.
Other Name: Folinic acid, Leucovorin Ca.
Biological: Cetuximab
Cetuximab will be given for the duration of radiotherapy. A loading dose of intravenous cetuximab at 400mg per square meter body-surface area will be given over two hours up to seven days prior to initiation of radiation treatments or on the day of the first treatment (drug information detailed below). Thereafter, cetuximab will be given weekly over 60 minutes at a dose of 250 mg per meter squared. Intravenous diphenhydramine (50 mg) will be given as premedication.
Other Name: Erbitux
Drug: Filgrastim
Neupogen®: 300 mcg/mL (1 mL, 1.6 mL). May be administered undiluted by SubQ injection. May also be administered by I.V. bolus over 15-30 minutes in D5W, or by continuous SubQ or I.V. infusion. Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
Other Name: Neupogen
Drug: Erythropoetin
Subcutaneous or intravenous
Other Name: Epogen®; Procrit®
Drug: Cisplatin
One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.
Other Name: Platinol AQ
Drug: Fluorouracil
One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.
Other Name: Fluorouracil
Drug: Docetaxel
One cycle of induction chemotherapy will be comprised of docetaxel on day 1 and cisplatin and 5-fluorouracil given days 1, 8, and 15. Intravenous docetaxel will be administered over one hour at a dose of 75 mg per square meter of body-surface area, followed by intravenous cisplatin at 35 mg per square meter, administered during a period of 0.5 to 3 hours weekly. After completion of the cisplatin infusion, intravenous fluorouracil will be given as a bolus at 1000 mg per square meter, followed by leucovorin at the dose of 350mg/m2. There will be total 4 cycles of chemotherapy of which 2 cycles will be prior to radiation therapy and 2 cycles will be post-radiation.
Other Name: Taxotere

Detailed Description:

Patients will be given two cycles of induction chemotherapy with Cisplatin, Docetaxel and Fluorouracil. This will be followed by six weeks of radiation therapy along with Cetuximab. Patients will get two more cycles of chemotherapy with the same agents after the completion of radiation therapy course. Patients will be watched very closely during the trial period, with close follow up of treatment responses and monitoring of any adverse effects.

  Eligibility

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

INCLUSION CRITERIA

  • Biopsy and/or fine needle aspirate of the tumor is required prior to registration. Pathologically confirmed primary squamous cell cancer of the oral cavity, oropharynx, hypopharynx, larynx, or unknown primary confined to the head and neck; histological variants such as spindle cell carcinoma, poorly differentiated keratin-positive carcinoma, and lymphoepithelioma are included. Patients with nasopharyngeal and salivary gland tumors are ineligible.
  • Measureable disease representing stage III or stage IVa or IVb cancer by AJCC staging is required (See Appendix II)
  • Measureable disease representing stage II cancer qualifies if the patient refuses surgery or is unable to undergo surgery as curative treatment
  • Patient must not have had previous irradiation or surgery other than biopsy of the head and neck region
  • A CT of the chest and CT or MRI of the tumor site is required within four weeks prior to registration
  • Appropriate staging evaluation is required within four weeks prior to registration, including the following:
  • history and physical examination with special attention to functional status measures, carotid arteries, neck and clavicular lymph nodes
  • chest CT with evaluation of any nodules ≥ 1cm with biopsy or PET/CT (patients with lesions < 1cm, negative on PET scan, or that cannot be safely biopsied remain eligible).
  • ECOG performance status 0-2 (See Appendix III)
  • Age ≥ 18 years
  • Complete blood count evaluation within two weeks of treatment demonstrating absolute neutrophil count ≥ 1500/mm3, platelets ≥100,000 cells/mm3, and hemoglobin ≥ 8g/dL
  • Liver function tests within two weeks of treatment demonstrating total bilirubin ≤1.5 mg/dL, AST and ALT < 2x upper limit of normal, and alkaline phosphatase < 2x upper limits of normal; an abdominal CT scan is required if any of the above criteria are not met
  • Adequate renal function measured within two weeks of treatment, defined as a creatinine clearance ≥ 50 ml/min determined by a 24 hour urine creatinine or the Cockcroft-Gault equation, where creatinine clearance (ml/min) is equal to:

[(140 - age) x (wt in kg)] x 0.85 for females [(sCR) x (72)]

  • Corrected serum calcium <11 mg/dL within two weeks prior to treatment.
  • Urine pregnancy test two weeks prior to treatment for women of childbearing potential; women of childbearing potential and male participants must agree to use a medically effective means of contraception throughout the duration of treatment and 30 days thereafter
  • All patients must sign study-specific informed consent prior to study entry.

EXCLUSION CRITERIA:

  • Evidence of metastatic disease
  • Prior head and neck cancer.
  • History of invasive cancer of any primary sight not considered cured.
  • Previous radiation to the head and neck
  • Nasopharyngeal or salivary gland cancer
  • Severe, active comorbidity, defined as:
  • New York Heart Association Class III or IV heart failure (Appendix IV)
  • Unstable angina
  • Acute bacterial or fungal infection requiring antibiotic treatment
  • Chronic obstructive pulmonary disease requiring long term oral steroids or hospitalization for exacerbation within three months of study registration
  • Liver dysfunction resulting in clinical jaundice or coagulation defects
  • Acquired Immune Deficiency Syndrome defined as CD4 count <200 or opportunistic AIDS defining infection requiring active antibiotic treatment
  • Pregnancy, lactation, or refusal of patient to take appropriate medical or behavioral measures to prevent pregnancy
  • Pre-existing peripheral neuropathy > grade 2
  • Hypersensitivity reaction to any drug listed in the protocol
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01467115

Contacts
Contact: Rene R Rubin, MD 2155610809 renerubin@hotmail.com

Locations
United States, Pennsylvania
Hahnemann University Hospital Recruiting
Philadelphia, Pennsylvania, United States, 19102
Contact: Rene R Rubin, MD    215-561-0809    renerubin@hotmail.com   
Sponsors and Collaborators
Drexel University
Investigators
Principal Investigator: Rene R Rubin, MD Drexel University
  More Information

Publications:

Responsible Party: Drexel University
ClinicalTrials.gov Identifier: NCT01467115     History of Changes
Other Study ID Numbers: 19834
Study First Received: November 4, 2011
Last Updated: February 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Drexel University:
loco regionally advanced
head and neck cancer
chemotherapy
radiation

Additional relevant MeSH terms:
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Docetaxel
Cetuximab
Cisplatin
Fluorouracil
Epoetin Alfa
Lenograstim
Leucovorin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Hematinics
Hematologic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 15, 2014