Study of Everolimus (RAD001) in Combination With Lenalidomide

Inclusion Criteria:

• Subjects must meet the following inclusion/exclusion criteria to be eligible for thestudy.
• Ability to understand and willingness to voluntarily sign an informed consent form.
• Histologic or cytologic confirmation of a solid malignancy.
• Age ≥ 18 years at the time of signing the informed consent form. Because no dosing oradverse event data are currently available on the use of everolimus in combinationwith lenalidomide in patients < 18 years of age, children are excluded from thisstudy.
• Able to adhere to the study visit schedule and other protocol requirements.
• Patients must have at least one measurable site of disease according to ResponseEvaluation Criteria in Solid Tumors (RECIST) criteria that has not been previouslyirradiated. If the patient has had previous radiation to the marker lesion(s), theremust be evidence of progression since the radiation.
• Diagnosed with advanced refractory solid malignancies or intolerant of standardtherapy for the stage of the disease (because there is currently no standard approvedtherapy for adenoidcystic carcinoma, therefore there is no requirement of priortherapy for this patient population).
• All previous cancer therapy, including radiation, hormonal therapy and surgery, musthave been discontinued at least 4 weeks prior to treatment in this study. A minimum of 6 weeks treatment break is required in case of nitrosoureas or mitomycin C.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 at study entry.
• Able to receive prophylactic anticoagulation with aspirin, warfarin or low molecularweight heparin when required for lenalidomide administration.
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5x upper limit of normal (ULN). NOTE: In case one or both of these thresholds areexceeded, the patient can only be included after initiation of appropriate lipidlowering medication.
• Laboratory test results within these ranges:
• Absolute neutrophil count 1500 ≥ /mm³
• Platelet count ≥ 100,000/mm³
• Hb ≥ 9 g/dL
• Creatinine within institutional limits of normal or creatinine clearance ≥ 60ml/min/m² if elevated creatinine
• Total bilirubin < 2.0 mg/dL or < 1.5.0 x ULN for the institution whichever ishigher
• Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) < 2.x ULN or < 5 x ULN if hepatic metastases are present.
• All study participants must be registered into the mandatory Revlimid Risk Evaluationand Mitigation Strategy (REMS®) program, and be willing and able to comply with therequirements of the REMS® program.
• Females of reproductive potential must adhere to the scheduled pregnancy testing asrequired in the Revlimid REMS® program.
• Females of childbearing potential (FCBP) must have a negative serum or urine pregnancytest with a sensitivity of at least 50 milli-International Unit (mIU)/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptionsmust be filled within 7 days) and must either commit to continued abstinence fromheterosexual intercourse or begin TWO acceptable methods of birth control, one highlyeffective method and one additional effective method AT THE SAME TIME, at least 28days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancytesting. Men must agree to use a latex condom during sexual contact with a FCBP evenif they have had a successful vasectomy.

Exclusion Criteria:

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements including signing the informed consent form.
• Pregnant or breast feeding females. (Lactating females must agree not to breast feedwhile taking lenalidomide).
• Any condition, including the presence of laboratory abnormalities, which places thesubject at unacceptable risk if he/she were to participate in the study or confoundsthe ability to interpret data from the study.
• Use of any other experimental drug or therapy within 28 days of baseline.
• Known hypersensitivity to thalidomide or everolimus (including other rapamycins,sirolimus and temsirolimus).
• The development of erythema nodosum if characterized by a desquamating rash whiletaking thalidomide or similar drugs.
• Prior treatment with lenalidomide or everolimus.
• Concurrent use of other anti-cancer agents or treatments.
• Patients known to be positive for HIV or infectious hepatitis, type B or C requiringactive therapy. Patients on combination antiviral therapy are ineligible because ofthe potential for pharmacokinetic interactions with everolimus and or lenalidomide. Inaddition, these patients are at increased risk of lethal infections when treated withmarrow-suppressive therapy. Appropriate studies will be undertaken in this patientpopulation.
• Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
• Symptomatic brain metastasis. Patients with treated brain metastasis must becompletely weaned off of steroid therapy for at least 14 days prior to startingprotocol therapy.
• Patients receiving chronic, systemic treatment with corticosteroids or anotherimmunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one weekof study entry or during study period.
• Diagnosed venous thromboembolic disease within the preceding 6 months (patient on fulldose or prophylactic anticoagulation are eligible).
• Patients receiving any medications or substances that are inhibitors or inducers ofCYP450 enzyme(s) are ineligible. Lists of excluded medications and substances known orwith the potential to interact with the cytochrome P450 (CYP450) enzyme(s) areprovided.
• History of other malignancies except: (i) adequately treated basal or squamous cellcarcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterinecervix, b) prostate cancer, or c) superficial bladder cancer; or (iii) othercuratively treated solid tumor with no evidence of disease for ≥ 3 years.
• Patients, who have had a major surgery or significant traumatic injury within 4 weeksof start of study drug, patients who have not recovered from the side effects of anymajor surgery (defined as requiring general anesthesia) or patients that may requiremajor surgery during the course of the study.
• Patients with an active, bleeding diathesis.