Study of Everolimus (RAD001) in Combination With Lenalidomide
Condition: Solid Organ Malignancies; Adenoidcystic Carcinoma; Neuroendocrine Tumors
MeSH terms: Carcinoma; Neoplasms; Neuroendocrine Tumors; Carcinoma, Adenoid Cystic
Intervention: Lenalidomide; Everolimus
Intervention description: Lenalidomide (10mg, 15mg, 20mg or 25mg) once daily by mouth, every day of each 28-day cycle.; 5mg or 10mg of everolimus administered once daily by mouth on a once daily continuous dosing schedule for 28 days.
Intervention MeSH terms: Lenalidomide; Everolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: kidney cancer; adenoidcystic cancer

Summary:

      The purpose of this study is to study the combination of two anticancer drugs, everolimus
      (RAD001) and lenalidomide in patients whose cancer is no longer responding to standard
      treatment or patients who are unable to tolerate the standard treatment for their cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must meet the following inclusion/exclusion criteria to be eligible for the
             study.

          -  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 or
             adverse event data are currently available on the use of everolimus in combination
             with lenalidomide in patients < 18 years of age, children are excluded from this
             study.

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  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.

          -  Diagnosed with advanced refractory solid malignancies or intolerant of standard
             therapy for the stage of the disease (because there is currently no standard approved
             therapy for adenoidcystic carcinoma, therefore there is no requirement of prior
             therapy for this patient population).

          -  All previous cancer therapy, including radiation, hormonal therapy and surgery, must
             have 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 molecular
             weight heparin when required for lenalidomide administration.

          -  Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5
             x upper limit of normal (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.

          -  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 ≥ 60
                  ml/min/m² if elevated creatinine

               -  Total bilirubin < 2.0 mg/dL or < 1.5.0 x ULN for the institution whichever is
                  higher

               -  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 Evaluation
             and Mitigation Strategy (REMS®) program, and be willing and able to comply with the
             requirements of the REMS® program.

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program.

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test 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 (prescriptions
             must be filled within 7 days) and must either commit to continued abstinence from
             heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 28
             days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
             testing. Men must agree to use a latex condom during sexual contact with a FCBP even
             if they have had a successful vasectomy.

        Exclusion Criteria:

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements including signing the informed consent form.

          -  Pregnant or breast feeding females. (Lactating females must agree not to breast feed
             while taking lenalidomide).

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the 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 while
             taking 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 requiring
             active therapy. Patients on combination antiviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with everolimus and or lenalidomide. In
             addition, these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in this patient
             population.

          -  Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

          -  Symptomatic brain metastasis. Patients with treated brain metastasis must be
             completely weaned off of steroid therapy for at least 14 days prior to starting
             protocol therapy.

          -  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.

          -  Diagnosed venous thromboembolic disease within the preceding 6 months (patient on full
             dose or prophylactic anticoagulation are eligible).

          -  Patients receiving any medications or substances that are inhibitors or inducers of
             CYP450 enzyme(s) are ineligible. Lists of excluded medications and substances known or
             with the potential to interact with the cytochrome P450 (CYP450) enzyme(s) are
             provided.

          -  History of other malignancies except: (i) adequately treated basal or squamous cell
             carcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterine
             cervix, b) prostate cancer, or c) superficial bladder cancer; or (iii) other
             curatively treated solid tumor with no evidence of disease for ≥ 3 years.

          -  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 with an active, bleeding diathesis.