A Phase I/II Study of the Use of Intensity Modulated Radiotherapy (IMRT) in Cancer of the Thyroid, Larynx and Hypopharynx

Study Overview
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Brief Summary
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This study is a phase I/II dose escalation trial designed to test the feasibility of delivering IMRT to thyroid, larynx and hypopharynx cancer patients, and to assess the safety and possible improvement in outcome when the dose is increased. This protocol is in fact two studies running in parallel: thyroid cancer patients and larynx/ hypopharynx cancer patients. These two groups of patients are being treated differently and will be analysed separately. The primary objective of this Phase I sequential cohort study was to determine the feasibility of delivering modest acceleration and dose-escalated IMRT in locally advanced high-risk thyroid cancers. We report the incidence and prevalence of acute toxicities of 2 dose fractionation regimens. DL1: primary site 58.8 Gy in 28 daily fractions and nodal levels 50 Gy in 28 daily fractions DL2: primary 66.6 Gy in 30 daily fractions and post operative nodal levels 60 Gy in 30 daily fractions and elective nodal levels 54 Gy in 30 daily fractions

Official Title
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A Phase I/II Study of the Use of Intensity Modulated Radiotherapy (IMRT) in Cancer of the Thyroid, Larynx and Hypopharynx

Conditions
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Locally Advanced Thyroid Cancers, Locally Advanced Larynx, Hypopharyngeal Squamous Cell Cancers

Intervention / Treatment
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* Radiation: Dose-escalated radiotherapy level 1
* Radiation: Sequential dose-escalated radiotherapy level 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed histologically confirmed squamous cell or undifferentiated carcinoma of the head and neck. Newly diagnosed histologically confirmed papillary,follicular, undifferentiated or medullary carcinoma of the thyroid. Tumours arising from the oral larynx or hypopharynx requiring radical radiation of the primary tumour by parallel opposed lateral fields, and bilateral cervical lymph node irradiation. High risk of radiation induced xerostomia with conventional radiotherapy due to the irradiation of the majority of both parotid glands (defined as estimated mean dose to both parotid glands greater than 26 Gy using conventional radiotherapy technique). Radiotherapy either as primary therapy or post-operative (only for thyroid carcinoma). Techniques to be detailed by each centre. Neo-adjuvant and concomitant chemotherapy are permitted. Stage T1-4, N1-3, M0 disease Zubrod Performance Status 0-2 Exclusion Criteria: Previous radiotherapy to the head and neck region Previous malignancy except non-melanoma skin cancer Previous or concurrent illness which in the investigators opinion would interfere with either completion of therapy or follow-up Prophylactic use of amifostine or pilocarpine is not allowed Brachytherapy is not allowed as part of the treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-escalated radiotherapy level 1<br> | Radiation: Dose-escalated radiotherapy level 1<br> <br> |
| Experimental: Sequential dose-escalated radiotherapy level 2<br> | Radiation: Sequential dose-escalated radiotherapy level 2<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the number of patients with grade 3 or 4 complication at 12 months after treatment. |  | 12 months after radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity |  | Up to 3 months after radiotheapy | 
| Late toxicity |  | Up to 60 months after radiotherapy | 
| Local control |  | Up to 60 months after radiotherapy | 
| Loco-regional control |  | Up to 60 months after radiotherapy | 
| Loco-regional disease free survival (disease free thyroid bed, neck and superior mediastinum) |  | Up to 60 months after radiotherapy | 
| Disease free survival |  | Up to 60 months after radiotherapy | 
| Overall Survival |  | Up to 60 months after radiotherapy |