Clinical trial NCT01283334 (phase 1/phase 2, status: completed)
Conditions: head and neck neoplasms, cancer of the head and neck
ICD codes: C76.0, C47.0, C49.0, C77.0, D17.0, D21.0, D36.11, C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2
Drugs: carboplatin, cetuximab, rad001
SMILES: N[C@@H](CCCNC(N)=N)C(O)=O, [H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C1=CSC(N)=N1)C(O)=O, [H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC
Eligibility criteria:

        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) < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most
             recent evaluation within 4 weeks of study entry.

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases. Patients with
             neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain
             metastasis.

          -  Patients currently receiving anticancer therapies or who have received anticancer
             therapies within 4 weeks of the start of study drug (including chemotherapy, radiation
             therapy, antibody based therapy, etc.).

          -  Prior treatment with any investigational drug within the preceding 4 weeks.

          -  Any unresolved toxicity (except alopecia) greater than NCI-Common Toxicity Criteria
             for Adverse Effects (CTCAE) v3.0 grade 2 from prior systemic anticancer therapy.

          -  Patients who have received prior treatment with a mammalian target of rapamycin (mTOR)
             inhibitor (sirolimus, temsirolimus, everolimus).

          -  Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins
             (sirolimus, temsirolimus) or to its excipients, or to cetuximab.

          -  Prior therapy with Cetuximab will be allowed provided it was part of definitive
             therapy and not part of treatment for recurrent or metastatic disease.

          -  Prior severe infusion reaction to a monoclonal antibody.

          -  Patients receiving chronic, systemic treatment with corticosteroids or another
             immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period.

          -  Patients, who have had a major surgery or significant traumatic injury within 4 weeks
             of start of study drug, patients who have not recovered from the side effects of any
             major surgery (defined as requiring general anesthesia) or patients that may require
             major surgery during the course of the study.

          -  Patients who have any severe and/or uncontrolled medical conditions or other
             conditions that could affect their participation in the study such as:

               -  Symptomatic congestive heart failure of New York heart Association Class III or
                  IV

               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial
                  infarction within 6 months of start of study drug, serious uncontrolled cardiac
                  arrhythmia or any other clinically significant cardiac disease

               -  Severely impaired lung function as defined as spirometry and diffusing capacity
                  of lung for carbon monoxide (DLCO) that is 50% of the normal predicted value
                  and/or 02 saturation that is 88% or less at rest on room air

               -  Uncontrolled diabetes as defined by fasting serum glucose >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 > 2.5 x ULN
             (except when LFTs attributed to metastatic SCCHN, in which case, TB, ALT and alkaline
             phosphatase must be ≤ NCI-CTCAE, v3.0 grade 1).

          -  Absolute neutrophil count < 1000/mm3 or platelets < 100,000/mm3.

          -  A known history of HIV seropositivity.

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of RAD001 (e.g., 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. If barrier contraceptives
             are being used, these must be continued throughout the trial by both sexes. Hormonal
             contraceptives are not acceptable as a sole method of contraception. (WOCBP must have
             a negative urine or serum pregnancy test within 7 days prior to administration of
             RAD001).

          -  History of noncompliance to medical regimens.

          -  Patients unwilling to or unable to comply with the protocol.