Chemotherapy Followed by Surgery, Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Head And Neck Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs such as gemcitabine and cisplatin may make tumor cells more sensitive to radiation therapy. Giving combination chemotherapy before surgery or radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving chemotherapy followed by surgery, chemotherapy, and radiation therapy works in treating patients with locally advanced head and neck cancer.

Detailed Description
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OBJECTIVES: Primary To assess the complete and overall response rate of neoadjuvant docetaxel, cisplatin, fluorouracil, and leucovorin calcium in previously untreated patients with local regionally advanced head and neck cancer. To evaluate the feasibility of a multimodality treatment approach with the goal of reducing long-term sequelae. To evaluate prospectively, the impact of neoadjuvant chemotherapy, concurrent chemoradiotherapy, and organ preservation surgery on overall survival, time to progression, and pattern of disease recurrence in these patients. To evaluate prospectively, biochemical correlates of response and prognosis, including markers such as thymidylate synthetase, ribonucleotide reductase, and ERCC1 (measured by quantitative PCR), p53 (evaluated by IHC), and HPV status and apoptosis (TUNEL assay). Secondary To evaluate treatment-associated morbidity with the use of a quality of life assessment tool. To compare the results of diagnostic salivary cytology with those of histopathology at initial diagnosis as well as follow-up in head and neck cancer patients. To evaluate the tolerability of combined chemoradiotherapy using gemcitabine and cisplatin after definitive surgery for squamous cell carcinoma of the head and neck. OUTLINE: Patients receive neoadjuvant induction chemotherapy comprising docetaxel IV over 1 hour on day 1 and cisplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on days 1-4. Induction chemotherapy repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response at the primary site may undergo radical or functional resection of the primary tumor within 3 weeks of completion of neoadjuvant therapy. Beginning within 4 weeks of completion of neoadjuvant therapy, patients with persistent disease or complete response after chemotherapy at the primary or neck then undergo radiotherapy 5 days a week for 7 weeks and receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes on day 1 of each week of radiotherapy in the absence of disease progression or unacceptable toxicity. Patients complete the FACT-H&N quality of life questionnaire at baseline and at completion of neoadjuvant therapy. Tissue biopsies are collected at baseline, periodically during therapy, at surgery, and after radiotherapy. Tissue is examined for gene and protein expression.

Official Title
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Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Drug: leucovorin calcium
* Genetic: gene expression analysis
* Genetic: protein expression analysis
* Other: laboratory biomarker analysis
* Procedure: adjuvant therapy
* Procedure: biopsy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Procedure: quality-of-life assessment
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the head and neck, including any of the following subtypes: Oral cavity Oropharynx Hypopharynx Larynx Stage III or IV disease Stage II carcinoma of the larynx, hypopharynx, or base of tongue allowed Measurable disease Resectable disease, defined as tumors that are potentially curable by surgery and radiotherapy PATIENT CHARACTERISTICS: Karnofsky performance status ≥ 60% ANC ≥ 1,500/μL Platelet count ≥ 100,000/μL Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min Bilirubin ≤ 1.5 mg/dL Transaminases and alkaline phosphatase meeting 1 of the following criteria: ALT or AST ≤ 2.5 times upper limit of normal (ULN) AND alkaline phosphatase normal Alkaline phosphatase ≤ 4 times ULN AND ALT and AST normal ALT or AST < 1.5 times ULN AND alkaline phosphatase < 2.5 times ULN Free of serious infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior malignancy allowed for purposes of determining disease-free or overall survival except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years No unstable angina, history of congestive heart failure, or acute myocardial infarction within the past 6 months No current symptomatic, neurosensory or neuromotor toxicity ≥ grade 2 No other significant medical or psychiatric condition incompatible with the protocol PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for head and neck cancer

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive neoadjuvant induction chemotherapy comprising docetaxel IV over 1 hour on day 1 and cisplatin IV, leucovorin IV, and fluorouracil IV over 24 hours on days 1-4. Induction chemotherapy repeats every 28 days for 3 courses. Patients with partial response at the primary site may undergo radical or functional resection of the primary tumor within 3 weeks of completion of neoadjuvant therapy. Beginning within 4 weeks of completion of neoadjuvant therapy, patients with persistent disease or complete response after chemotherapy at the primary or neck then undergo radiotherapy 5 days a week for 7 weeks and receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 60 minutes on day 1 of each week of radiotherapy. | Drug: cisplatin<br> <br> Drug: docetaxel<br> <br> Drug: fluorouracil<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> Genetic: gene expression analysis<br> <br> Genetic: protein expression analysis<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: biopsy<br> <br> Procedure: conventional surgery<br> <br> Procedure: neoadjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response | Complete response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial response (PR): Greater than or equal 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. Overall Response (OR) = CR + PR. | 30 days after last course of treatment | 
| Progression-free Survival | Estimated using the product-limit method of Kaplan and Meier. Progression defined as a 50% increase or an increase of 10 cm^2 (whichever is smaller) in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion that had disappeared, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition. Progression-free survival defined as from first day of treatment until the date of first documented progression or date of death from any cause, whichever came first. If failure has not occurred, failure time is censored at the time of last follow-up. | From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 171 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage III squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage II squamous cell carcinoma of the larynx, stage II squamous cell carcinoma of the hypopharynx, stage II squamous cell carcinoma of the oropharynx