A Study of Carboplatin, Cetuximab and RAD001 in Advanced Head and Neck Cancer

Inclusion Criteria

• Patients must have at least one measurable site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria that has not been previously irradiated. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Histologically or cytologically proven squamous cell carcinoma of the head and neck (SCCHN).
• Patients with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, and unknown primary SCCHN who failed to respond to, or relapsed from prior chemoradiotherapy for definitive treatment of disease.
• Evaluable locoregional and/or metastatic disease according to RECIST criteria (see Section 6) that is not appropriate for treatment by primary surgical resection or radiotherapy.
• Patients may not have had prior chemotherapy for recurrent or metastatic disease.
• Patients must not be candidates for curative therapy.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Life expectancy of ≥ 4 months.
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hemoglobin ≥ 9.0/dl
• Absolute-neutrophil count (ANC ) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)
• International normalized ratio (INR) ≤ 1.5 or a prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for > 2 weeks at time of randomization)
• Creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to first receiving investigational product. Sexually active women of childbearing potential (WOCBP) must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation.
• Signed informed consent prior to beginning protocol specific procedures. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial.

Exclusion Criteria

• History of prior malignancy within the past 5 years except for curatively treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical intraepithelial neoplasia (CIN) or localized prostate cancer with a current prostate-specific antigen (PSA) 1.5 x ULN
• Active (acute or chronic) or uncontrolled severe infections
• Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Abnormal liver function tests (LFTs) as follows: total bilirubin (TB) > 1.5x ULN, alanine aminotransferase (ALT) > 1.25x ULN, and/or alkaline phosphatase > 2.