Everolimus Versus Placebo in Head and Neck Cancer

Study Overview
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Brief Summary
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Primary: Two-year progression-free (tumor does not grow or spread) survival in subjects treated with everolimus versus placebo after definitive local therapy.

Official Title
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Randomized Phase II Trial of Everolimus Versus Placebo as Adjuvant Therapy in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck (SCCHN)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Everolimus (RAD 001)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Squamous cell carcinoma of the head and neck (stage IVa or IVb). No evidence (absence)of disease by scan. 18 years or older. Performance status 70% or better. Adequate marrow, renal and liver function (will be tested by labs). _ Able give consent. Exclusion Criteria: Currently receiving anti-cancer treatment. Major surgery or traumatic injury within 4 weeks. Radiotherapy related toxicities. Lip, nasopharynx, nasal cavity, paranasal sinus, salivary gland, skin, or thyroid primary tumors Receiving other investigational drugs. Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Receive immunization with attenuated live vaccines (seasonal flu shot)1 week before starting this . Show evidence of disease (cancer). Uncontrolled medical conditions such as: unstable angina, congestive heart failure, diabetes, severely impaired lung function. Liver disease such as cirrhosis, severe hepatic impairment, Hepatitis B or C. Active, uncontrolled severe infections Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. Known History of HIV positivity. Impaired gastrointestinal function that may alter absorption of Everolimus such as ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection. Patients with an active, bleeding diathesis. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. ) Male patient whose sexual partner(s) are Women of child bearing potential who are not willing to use adequate. contraception, during the study and for 8 weeks after the end of treatment Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus). Patients with a known hypersensitivity to Everolimus or other rapamycin analogues (sirolimus, temsirolimus) or to its excipients. History of noncompliance to medical regimens. Patients unwilling to or unable to comply with the protocol.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Everolimus (RAD001)<br>Subjects will receive Everolimus 10 mg daily | Drug: Everolimus (RAD 001)<br>* 10mg of Everolimus or Placebo taken by mouth once daily for 1 year or until progression (whichever comes first).<br>|
| Experimental: Placebo<br>Subjects will receive double-blind placebo | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 Year Progression Free Survival Rate | Time to disease progression or death from any cause--2 year rate | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Toxicity | Adverse event rate, any type, any grade regardless of attribution | 4 years | 
| Site of Progression: Local-regional | Number of patients with local-regional progression | 4 years | 
| Site of Progression: Distant | Number of patients with distant progression | 4 years | 
| Site of Progression: Unknown | Number of patients with unknown site of progression | 4 years | 
| Second Primary Tumor | Number of patients with second primary tumor | 4 years | 
| Akt/mTOR Pathway Activation | mTOR positive in tumor tissue | Baseline | 
| Correlation of Akt/mTOR Status With Progression-free Survival | mTOR positive in tumor tissue | 4 years | 
| Determine if PTEN Status is a Predictive Biomarker | Differential effect of PTEN status on progression-free survival between the two arms | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous Cell Cancer