Cetuximab + Taxotere With Low Dose Fractionated Radiation for Head and Neck Carcinoma

Study Overview
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Brief Summary
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Whether low-dose radiation in addition to Taxotere and Erbitux improves the response rate of patients with recurrent unresectable head and neck squamous cell carcinoma.

Detailed Description
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The investigator's approach is based on the following reasons: Low dose hyper-radiation sensitivity response will be significantly enhanced in Taxotere- induced G2/M cell cycle arrest. LDFRT will render enhanced bax activation mediated mode of cell death. Erbitux will arrest the cells in G1/G0 phase leading to p21-mediated mode of cell death. The toxicity profile is expected to be minimal. Based on the above mentioned reasons, we propose this novel schema of treatment in recurrent SCCHN.

Official Title
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Phase II Trial Using Erbitux+ Taxotere With Low Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck Carcinoma

Conditions
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Squamous Cell Carcinoma, Head and Neck Cancer, Recurrent Disease

Intervention / Treatment
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* Drug: Erbitux
* Drug: Taxotere
* Radiation: Low Dose Fractionated Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have pathologically confirmed recurrence (reappearance of previously cleared) squamous cell cancer primary in the upper aerodigestive tract .Patients may have experienced more than one recurrence as long as the first recurrence occurred ≥ 6 months following the end of the prior RT. The recurrence must have defined bi- or uni-dimensional measurements. Recurrence must be confined to the head and neck above the clavicles (loco-regional recurrence). The patient must not be a candidate for surgical resection. Patients must be at least 6 months from completion of prior chemotherapy and radiation therapy. Patients may have received prior chemotherapy as a component of their primary treatment, but not for recurrent disease. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Granulocytes ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum bilirubin ≤ 1.5 mg/dl, creatinine < 1.5 mg/dl within 3 weeks prior to registration. Liver Function Tests (LFTs) ≤ 2 x normal (serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic-pyruvic transaminase (SGPT)/Alkaline Phosphatase). If > 2 x normal, liver ultrasound or CT is required to exclude metastases. If negative for metastases, patients are eligible. Patients must sign a study-specific informed consent form prior to study entry. Exclusion Criteria: Distant metastases outside of the head and neck. Primary disease in the nasopharynx or the salivary gland. Other concurrent invasive malignancies. Prior invasive malignancy unless disease free for at least two years (except prior in situ malignancies, e.g. cervix, breast, non-melanomatous skin cancer, etc. are permissible). Intercurrent medical illnesses which would impair patient tolerance to therapy or limit survival. Pre-existing grade ≥ 2 peripheral sensory neuropathy Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns. Prior history of sever hypersensitivity reaction to Docetaxol, Cetuximab or a drug with formulated with Polysorbate 80.
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: Erbitux, Taxotere, LD Fractionated RT<br>Erbitux, Taxotere and Low Dose Fractionated Radiation Therapy (LDFRT) | Drug: Erbitux<br>* Erbitux: 400 mg/m2 as a loading dose one week prior to radiation and taxotere, and then at 250 mg/m2 given weekly on Day 1 of treatment week following Taxotere.<br>* Other names: Cetuximab;Drug: Taxotere<br>* Taxotere : 20 mg/m2 IV once a week on Day 1 during treatment weeks 2 to 7.<br>* Other names: Docetaxel;Radiation: Low Dose Fractionated Radiation Therapy<br>* Low-dose fractionated Radiation (LDFRT): 0.5 Gy per fraction twice-a-day (BID) at least 6 to 8 hours apart on Days 2 and 3 of treatment weeks 2 to 7 for a total dose of 12 Gy.<br>* Other names: LDFRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of Participants | ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. | Up to 6 months from End of Treatment, about 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Study Participants Experiencing Treatment-Related Toxicity | Assess the safety profile (acute and late toxicities) of the proposed treatment. Number of study participants experiencing treatment-related acute and late toxicity: Acute toxicity is defined as toxicity occurring within 90 days of start of therapy. Late/Long-term toxicity defined as toxicity occurring more than 90 days after start of therapy. | Up to 6 years | 
| Estimated Progression-Free Survival (PFS) | Progression-free survival (PFS) is defined of the length of time from the start date of treatment to the earliest documented occurrence of disease progression according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. In the absence of an event constituting failure, follow up time will be censored at the date of last disease assessment. | Up to 6 years | 
| Estimated Overall Survival (OS) | Overall survival (OS) is defined as the length of time from the start of treatment that study participants diagnosed with the disease are still alive. OS will be measured from the start date of treatment to the date of death or last contact (censored observations). | Up to 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCCHN, Head and Neck Cancer, Squamous Cell Carcinoma, Recurrent