Docetaxel, Cetuximab and Cisplatin Followed by Radiation, Cetuximab and Cisplatin in Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine if the addition of a unique targeted agent called Cetuximab (also known as C225 and Erbitux) can increase the effectiveness of standard treatment with chemotherapy and radiation.

Detailed Description
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This research study involves the use of a combination of two chemotherapies, cisplatin and docetaxel, which have been known to shrink head and neck cancers and are a commonly used treatment for this type of cancer. This combination will then be followed by radiation and more chemotherapy. The purpose of this study is to see whether this combination of chemotherapy and radiation, with the addition of Cetuximab, can improve control of disease and collect information on what side effects this combination therapy may have. In addition, biologic factors (markers) will be studied that may help to predict and treat head and neck cancer patients in the future.

Official Title
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A Phase II Trial of Docetaxel, Cetuximab (C225), and Cisplatin Followed by Radiation, Cetuximab, and Cisplatin in Locally Advanced Head and Neck Cancer

Conditions
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Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Cisplatin
* Drug: Cetuximab
* Procedure: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage III-IVB head and neck cancer, all sites, including unknown primary tumors (bulky stage II (T2N0) lesions of the base of tongue or hypopharynx and patients with stage II nasopharyngeal cancer are also eligible) Prior to study entry the resectability and alternative treatment options will be determined by a team composed of an Ear, Nose, and Throat Surgeon, a Radiation Oncologist and a Medical Oncologist. Stage determination, optimal local treatment, and its timing according to this protocol will be determined at this evaluation. Unequivocal demonstration of distant metastasis (M1) confers ineligibility Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas, or WHO types I-III of the nasopharynx Unidimensionally-measurable disease is required (RECIST) No prior chemotherapy, biologic/molecular targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer 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 (Any non-biopsy procedure must have taken place > 4 weeks but < 3 months of initiating protocol treatment) ECOG PS 0 or 1; 7. Organ & marrow function per protocol criteria and 8. Age of >=18 years Exclusion Criteria: History of severe allergic reactions attributed to docetaxel or compounds of similar chemical or biologic composition to docetaxel, or other drugs formulated with polysorbate 80 Uncontrolled intercurrent illness or significant history of uncontrolled cardiac disease Receiving any other investigational agents No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 5-year disease-free survival Significant baseline sensory or motor neurologic deficits (> grade I neuropathy); 6. HIV-positive patients and 7. Prior severe infusion reaction to a monoclonal antibody.

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: Head and neck cancer patients<br>Induction chemotherapy consists of 3 cycles of cisplatin 75 mg/m^2, on day 1, docetaxel 75 mg/m^2, on day 1, and cetuximab weekly days 1,8,15, repeated every 21 days (cetuximab dose is 400 mg/m^2 on day 1 and 250 mg/m^2 on subsequent weekly treatments). After 3 cycles of induction, patients receive standard radiation 70 Gy/200 cGy/daily, 5 days/week with concurrent weekly cisplatin 30 mg/m^2 and cetuximab 250 mg/m^2. After completing radiation therapy, patients receive cetuximab weekly as maintenance therapy for 6 months (see section 5 for detailed treatment plan and dose modifications) | Drug: Docetaxel<br>* Docetaxel 75 mg/m^2 IV over 1 hour, day 1<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m^2 IV over 1-2 hours, day 1, 1 hour following completion of cetuximab infusion.<br>Drug: Cetuximab<br>* Cetuximab dose will be 250 mg/m^2 IV over 60 minutes weekly on ALL subsequent administrations (days 8 and 15 of cycle 1 and days 1,8,15 of cycles 2 and 3).<br>* Other names: (Erbitux or C225);Procedure: Radiation Therapy<br>* Photon energies of 1.25 to 6 MV and/or appropriate electron energies for boosting the nodes are allowed. Photon energies>6 MV may be utilized when appropriate to boost target localized centrally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. | Up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. | Up to 36 months | 
| Progression-free Survival (PFS) | PFS is an estimated percentage of participants without disease progression at two years (or three years) after the start of study treatment. Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. The two-year and three-year PFS ended up being the same in this study. | Up to 36 months | 
| 2-year Overall Survival (OS) | Two-year OS is an estimated percentage of participants still living at two years after the start of study treatment. | Up to 24 months | 
| 3-year Overall Survival (OS) | Three-year OS is an estimated percentage of participants still living at three years after the start of study treatment. | Up to 36 months | 
| Quality of Life (QOL) | Effect of treatment on acute and late QOL and functional status using Functional Assessment of Cancer Therapy-General (FACT-G) with FACT-Head and Neck (FACT-HN) subscale. The instructions to the participant were: Below is a list of statements that other people with your illness have said are important. By circling one number per line, please indicate how true each statement has been for you during the past 7 days. The choices for each statement ranged from 0 (not at all) to 4 (very much). The FACT-G and FACT-Head and Neck total scores were computed by summing 27 and 39 questions respectively, for four subscales: physical well-being, social well-being, emotional well-being, and functional well-being. Questions for both assessments are phrased so that higher numbers/values indicate a better health state. | Pre-treatment, Post-induction, 3 months after XPE and 12 months after XPE | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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head, neck