DREXNECK: Induction Chemotherapy Followed by Cetuximab and Radiation Therapy for Head and Neck Cancer

Sponsor

Drexel University College of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT01467115

Collaborator

(none)

Enrollment

Location

Arm

55.2

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Radiation: Radiotherapy Drug: Leucovorin Biological: Cetuximab Drug: Filgrastim Drug: Erythropoetin Drug: Cisplatin Drug: Fluorouracil Drug: Docetaxel	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Induction Chemotherapy With Taxotere, Cisplatin and 5-Fluorouracil Followed by Concomitant Cetuximab and Radiation for Locoregionally Advanced Squamous Cell Cancer of the Head and Neck: A Phase II Trial

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Jun 1, 2014

Actual Study Completion Date :

Oct 7, 2014

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: 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 Names: Neupogen Drug: Erythropoetin Subcutaneous or intravenous Other Names: 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 Names: 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. 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 Names: Taxotere

Arm

Intervention/Treatment

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 Names:

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 Names:

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 Names:

Neupogen

Drug: Erythropoetin

Subcutaneous or intravenous

Other Names:

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 Names:

Platinol AQ

Drug: Fluorouracil

Drug: Docetaxel

Other Names:

Taxotere

Outcome Measures

Primary Outcome Measures

Organ Sparing Survival [3 years]
to determine whether the intervention will prolong survival without needing salvage surgery (organ sparing survival)

Secondary Outcome Measures

Overall Survival [3 years]
we will determine if the intervention prolongs overall survival.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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