Neoadjuvant Cisplatin/Docetaxel (CDDP/TXT) and Chemoradiation for Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and safety of neoadjuvant chemotherapy (chemotherapy given before radiotherapy) using cisplatin and docetaxel, followed by carboplatin given at the same time as radiotherapy in the treatment of locally advanced head and neck cancer.

Detailed Description
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Chemoradiotherapy has become the standard of care for patients with unresectable head and neck cancer, but there can be substantial added toxicity with chemoradiotherapy compared to radiation therapy alone. Neoadjuvant therapy with cisplatin / 5-fluorouracil has demonstrated activity in this disease, and taxanes appear to improve response further. Docetaxel / cisplatin / 5-fluorouracil has been shown to be a highly active regimen. However, with the potential added toxicities of neoadjuvant chemotherapy, it is important to minimize toxicity while maintaining efficacy. Chemotherapeutic agents that are DNA cycle-specific like 5-fluorouracil are more stomatotoxic than those that are cell phase non-specific. Of note, several studies have suggested that docetaxel and cisplatin is a highly active combination when used for advanced disease or as neoadjuvant therapy . This study will therefore test the efficacy of neoadjuvant chemotherapy with cisplatin and docetaxel without 5-fluorouracil followed by chemoradiotherapy with carboplatin to determine whether promising response rates with modest toxicity can be achieved. Carboplatin will be used as the radiosensitizing agent during chemoradiotherapy to reduce nephrotoxicity and neurotoxicity as compared to further treatment with cisplatin.

Official Title
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A Pilot Study to Evaluate Response to Neoadjuvant Chemotherapy With Cisplatin and Docetaxel Followed by Chemoradiation Therapy With Carboplatin in Stage IV Non-metastatic Head and Neck Cancer

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Drug: Docetaxel/cisplatin
* Radiation: Radiotherapy
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven locoregional Stage 4 squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx Measurable or evaluable disease No distant metastases Tumor should be surgically unresectable for cure or resection is considered inadvisable Age > 18 years ECOG performance status 0, 1 or 2 Life expectancy > 2 months Patients must have adequate organ and marrow function as defined below: Leukocytes > 3,000/mm3 Absolute neutrophil count > 1,500/mm3 Platelets > 100,000/mm3 Hemoglobin > 10.0g/dL Total Bilirubin <= institutional upper limit of normal Aspartate aminotransferase < 2.5 X institutional upper limit of normal Alanine aminotransferase < 2.5 X institutional upper limit of normal Alkaline phosphatase < 2.5 X institutional upper limit of normal Creatinine <= institutional upper limit of normal OR creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine > institutional upper limit of normal Signed informed consent Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment Exclusion Criteria: Previous chemotherapy for this malignancy Previous radiotherapy to head and neck region Other malignancy within last 5 years except for non-melanoma skin cancer Uncontrolled intercurrent illness that would prevent delivery of protocol therapy Peripheral neuropathy > Grade 2 Hypercalcemia Patient is pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 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: Neoadjuvant/Concomitant Chemoradiation<br>Three cycles of docetaxel/carboplatin neoadjuvant chemotherapy followed by chemoradiotherapy for 7 weeks with weekly carboplatin | Drug: Docetaxel/cisplatin<br>* Docetaxel 75 mg/m2 intravenous every 3 weeks for 3 cycles Cisplatin 75 mg/m2 intravenous every 3 weeks for 3 cycles<br>* Other names: Platinol;Radiation: Radiotherapy<br>* 70 Gy in 35 fractions to gross tumor and lymph node metastases<br>* Other names: Radiation therapy;Drug: Carboplatin<br>* Carboplatin AUC 1.5 intravenous weekly during radiotherapy<br>* Other names: Paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer |  | 6 months after initiation of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate to neoadjuvant chemotherapy with docetaxel/cisplatin in locally advanced squamous head and neck cancer |  | 3 months after initiation of therapy | 
| Response rate to chemoradiotherapy in locally advanced squamous head and neck cancer |  | 6 months after initiation of therapy | 
| Toxicity of neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer |  | Every 3 weeks for 6 months (during therapy) | 
| Progression free survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer |  | Every 6 months | 
| Overall survival after neoadjuvant chemotherapy with docetaxel/cisplatin, followed by chemoradiotherapy in locally advanced squamous head and neck cancer |  | Every 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined Modality Therapy, Neoadjuvant Therapy, Head and neck neoplasms