Everolimus, Carboplatin, and Paclitaxel in Locally Advanced Head and Neck Cancer That Cannot Be Removed by Surgery (CAPRA)

DISEASE CHARACTERISTICS:

• Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx

  • Locally advanced disease (T4 N0-N3 disease)
  • Unresectable disease OR resectable disease with surgery contra-indication
  • No stage I, II, III, or IVc disease
• Measurable lesions defined as those accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥ 10 mm with spiral CT scan
• No known brain metastases (cerebral CT scan is not required if no symptom is present)

PATIENT CHARACTERISTICS:

• WHO performance status 0-2
• Life expectancy > 3 months
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.25 times upper limit of normal (ULN)
• Transaminases ≤ 2.5 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Creatinine clearance ≥ 60 mL/min
• Glycemia ≤ 1.5 times ULN
• Cholesterol level ≤ 7.30 mmol/L
• Serum total protein normal
• Oxygen saturation > 88%
• Able to swallow pills
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment
• No preexisting neuropathy ≥ grade 2

• No uncontrolled disease including any of the following:

  • Diabetes
  • Hypertension
  • Symptomatic congestive heart or pulmonary failure
  • Renal or hepatic chronic disease
  • Severe infectious disease
• No active hemorrhagic syndrome
• No prior history of cancer within the past 5 years, except in situ cervical cancer and basal cell skin carcinoma
• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Registration in a national health care system (CMU included)
• Not eligible for organ preservation program

PRIOR CONCURRENT THERAPY:

• No prior therapy for this cancer
• No prior chemotherapy unless received for treatment of another primary tumor considered in remission
• No prior investigational drug
• More than 30 days since prior participation in another therapeutic trial
• No prior or concurrent radiotherapy (except anterior radiotherapy) unless received for treatment of another primary tumor considered in remission
• No concurrent CYP3A4 strong inhibitors (e.g., azole antimycotics [itraconazole, ketoconazole], HIV protease inhibitor [ritonavir], erythromycin, anti-epileptic drugs [phenytoin, carbamazepine])
• No concurrent anti-coagulant therapy