A Study of Chemo +/- Low-dose Radiation as Induction Therapy in SCCHN

Study Overview
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Brief Summary
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The primary hypothesis of this study is that hyper-radiosensitivity (HRS) seen at extremely low doses of radiation can be exploited to enhance the effect of chemotherapy, and that this effect differs from the cellular effect of higher, standard fractions of radiation used in traditional radiation treatment paradigms.

Official Title
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A Phase II Study of Docetaxel, Carboplatin With and Without Low Dose Radiation as Induction Therapy in Locally Advanced Head and Neck Cancer

Conditions
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Larynx, Head and Neck Cancer

Intervention / Treatment
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* Radiation: Low dose fractionated radiation - 80cGy with chemotherapy
* Drug: Docetaxel and Carboplatin AUC 6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced head and neck cancer of squamous type stage III, IVA and IV B and select Stage II tumors of the BOT who are appropriate for potentially curative therapy with chemoradiotherapy. Measurable disease. ECOG performance status of 0, 1 or 2 No prior chemotherapy for the current locally advanced SCCHN. Age ≥18 years. Life expectancy of greater than 3 months Normal organ and marrow function measured within 14 days of registration as defined below: absolute neutrophil count ≥ 1,000/mcL platelets ≥ 100,000/mcL total bilirubin < institutional upper limit of normal AST(SGOT ≤ 2.5 × institutional upper limit of normal Alkaline phosphatase ≤ 2.5 × institutional upper limit of normal creatinine within normal institutional limits OR o Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, throughout the duration of active treatment and for 4 months after completion of chemotherapy and radiation. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of active study treatment, and for 4 months after completion of chemotherapy and radiation (both induction and definitive) administration. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior chemotherapy for SCCHN Patients who are receiving any other investigational agents. Patients with known brain metastases History of allergic reactions attributed to compounds of similar chemical or biologic composition to Carboplatin or Docetaxel. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant women HIV-positive patients on combination antiretroviral therapy Other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated previous Stage I or II cancer from which the patient is currently in complete remission or other cancer from which the patient has been disease-free for 3 years. Patients with nasopharynx or salivary gland primary site Patients with distant metastatic disease (M1c) Patients with grade II or greater peripheral neuropathy

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy plus Radiation Therapy<br>Low dose fractionated radiation - 80cGy with chemotherapy | Radiation: Low dose fractionated radiation - 80cGy with chemotherapy<br>* Chemotherapy + 80 cGy of RT<br>|
| Active Comparator: Chemotherapy without Radiation<br>Chemotherapy only | Drug: Docetaxel and Carboplatin AUC 6<br>* Docetaxel 75 mg/m2 and Carboplatin AUC 6 without Radiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Site Complete Response Rate | Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment. | Up to 50 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | To assess overall response rate of patients to 2 cycles of induction Docetaxel and Carboplatin with or without LDFRT. Response assessment was Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and Progressive Disease (PD): > 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (Note: the appearance of one or more new lesions is also considered progression). | Up to 50 days | 
| Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. | Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey. Physical; scores range from 7-35; higher scores indicate increased well-being Social/family; scores range from 7-35; higher scores indicate increased well-being Emotional; scores range from 6-30; higher scores indicate increased well-being Functional; scores range from 7-35; higher scores indicate increased well-being Additional Concerns; scores range from 10-50; lower scores indicate increased well-being FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being | Up to 50 days (pre- and post-treatment) | 
| 3-year Overall Survival | 3-year overall survival | From date of randomization until date of death from any cause, assessed up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Low dose radiation