Docetaxel/Cisplatin/5-Fluorouracil (TPF) Human Papillomavirus (HPV) Squamous Cell Carcinoma Study

Study Overview
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Brief Summary
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In this research study, the investigators are studying whether a reduced dose of radiation when given with standard doses of chemotherapy can reduce side effects without compromising control of the cancer. An approved treatment for squamous cell carcinoma of the head and neck is initial chemotherapy followed by radiation and chemotherapy together. This treatment is effective but has many immediate and long-term side effects. People who have squamous cell carcinoma of the head and neck (SSCHN) that is related to an infection by the human papillomavirus (HPV) have been shown to have a high response to this treatment along with a high cure rate. The investigators think that by reducing the intensity of this treatment, they may be able to reduce immediate and long-term side effects which may lead to long term improvements in quality of life and function.

Detailed Description
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OBJECTIVES: Primary To determine rate of local-regional control at 2 years Secondary To determine Progression Free Survival at 2 and 5 years To determine Overall Survival at 2 and 5 years To assess acute toxicity and long term toxicity of reduced radiation dose at 2 and 5 years

Official Title
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A Phase II Study of Docetaxel/Cisplatin/5-Fluorouracil (TPF) Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Using a Modified Radiation Dose in Patients With Newly Diagnosed HPV Positive, Locally Advanced Squamous Cell Carcinoma of the Oropharynx

Conditions
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Squamous Cell Carcinoma of the Head and Neck, Human Papilloma Virus

Intervention / Treatment
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* Drug: docetaxel
* Drug: cisplatin
* Drug: 5-FU
* Radiation: IMRT
* Drug: cetuximab
* Drug: carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically or cytologically confirmed squamous cell carcinoma of the oropharynx or unknown primary that is HPV 16 positive as determined by ISH and p16 positive as determined by IHC. Stage 3 or 4 disease without evidence of distant metastases At least one evaluable or uni- or bi-dimensionally measurable lesion by RECIST 1.1 criteria 18 years of age or older No previous surgery, radiation therapy or chemotherapy for SSCHN is allowed at time of study entry ECOG Performance Status of 0 or 1 No active alcohol addiction Adequate bone marrow, hepatic and renal function as defined in the protocol Women of child-bearing potential must have a negative pregnancy test within 7 days of starting treatment Exclusion Criteria Pregnant or breast feeding women or women and men of childbearing potential not willing to use adequate contraception while on treatment and for at least 3 months after Previous or current malignancies at other sites Symptomatic peripheral neuropathy of grade 2 or greater Symptomatic altered hearing greater than grade 2 Other serious illnesses or medical conditions Patients that have experienced an involuntary weight loss of more than 25% of their body weight in the 2 months preceding study entry Concurrent treatment with any other anticancer therapy Participation in an investigational trial within 30 days of study entry

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: TPF Induction Chemotherapy followed by Chemoradiotherapy<br>Patients received 3 cycles (21 days each) of TPF induction chemotherapy: docetaxel 75 mg/m2 IV day 1; cisplatin 100 mg/m2 IV day 1 (carboplatin substitute permitted); 5-FU 1000 mg/m2/day IV pump continuous days 1-4. Concurrent chemoradiotherapy followed 4-6 weeks after day 1 of cycle 3 TPF induction: cetuximab 400 mg/m2 IV loading dose 1 week prior and 250 mg/m2 IV weekly (panitumumab substitute permitted); carboplatin AUC 1.5 (Calvert formula) IV weekly; Intensity modulated radiation therapy (IMRT)-response based dosing for 6-7 weeks. | Drug: docetaxel<br> <br> * Other names: Docefrez;Drug: cisplatin<br>* Given intravenously on day 1 of each cycle<br>* Other names: Platinol-AQ;Drug: 5-FU<br> <br> * Other names: 5-fluorouracil;Radiation: IMRT<br> <br> * Other names: Intensity modulated radiation therapy;Drug: cetuximab<br> <br> * Other names: Erbitux;Drug: carboplatin<br> <br> * Other names: Paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-Year Local-Regional Control Rate | 2-year local-regional control rate is defined as the proportion of participants who achieve confirmed stable disease (SD) or better by 2-years post study registration based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. SD is neither PR nor PD. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | Follow-up for response continued until first progression. Disease assessments occurred at completion of induction cycle 3 along with months 12, 18 and 24 post study registration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-y Overall Survival Rate | 4-year overall survival rate is the percentage of patients remaining alive 4-years from study entry. | Patients were followed for survival up to 5 years from study entry. Patients alive have been followed for a mean of 55 months (range 52-60 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SSCHN, HPV, IMRT