Clinical trial NCT00402415 (phase 1, status: terminated)
Conditions: tumors
ICD codes: E88.3, R97.8, C49.A0, C49.A1, C49.A2, C49.A5, C49.A3
Drugs: sunitinib malate, rapamycin
SMILES: CCN(CC)CCNC(=O)C1=C(C)NC(\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C, [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 histologically confirmed malignancy that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective. Patients with previously untreated metastatic renal cell
             carcinoma are eligible.

          -  Patients must have measurable disease by RECIST criteria.

          -  Patients must have at least 1 lesion located in the neck, lung, solid organ (including
             liver) or soft tissue in abdomen or pelvis, or soft tissue in lower extremities that
             is 3 cm and ideally <7 cm in the transaxial plane. Larger lesions may be considered if
             they meet all other criteria. Index lesions must be well demarcated.

          -  ECOG performance status of 0-1.

          -  Must be ≥18 years of age.

          -  Expected survival of at least 3 months.

          -  Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically
             sterile) must use acceptable contraceptive methods (abstinence, intrauterine device
             [IUD], oral contraceptive or double barrier device), and must have a negative serum or
             urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing
             patients are excluded. Sexually active men must also use acceptable contraceptive
             methods. Pregnant and nursing patients are excluded because the effects of the
             combination of SU11248 (Sutent®) and sirolimus on a fetus or nursing child are
             unknown.

          -  Must be able and willing to give written informed consent.

          -  Patients must have the following clinical laboratory values: ANC count ≥1500/mm3;
             Platelets ≥100,000/mm3; Serum creatinine ≤2x upper limit of normal. If serum
             creatinine is above the upper limit of normal (but less than 2x normal), patients must
             have a measured 24 hour urine creatinine clearance ≥ 50 ml/min to be eligible; Total
             bilirubin < 1.5x upper limit of normal; Serum calcium < 12.0 mg/dl; Alanine
             aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x the upper limit of
             normal; Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR in
             the normal range;. Hemoglobin ≥9 gm/dl (may be corrected by transfusion).

          -  Normal cardiac ejection fraction

        Exclusion Criteria:

          -  Diagnosis or history of central nervous system (CNS) disease (i.e. primary brain
             tumor, malignant seizures, CNS metastases or carcinomatous meningitis).

          -  Any active uncontrolled bleeding and any patient with a bleeding diathesis (for
             example, active peptic ulcer disease). Any grade 3 hemorrhage within 4 weeks prior to
             starting treatment.

          -  Any ongoing coagulopathies or receiving anticoagulants.

          -  Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
             medical therapy).

          -  QTc interval > 500 msec on baseline EKG.

          -  Cardiac ejection fraction below institutional lower limit of normal.

          -  Measured 24-hour urine creatinine clearance < 50 ml/min.

          -  Active infection of any kind.

          -  Unwilling or unable to follow protocol requirements or to give informed consent.

          -  Dyspnea at rest or with minimal exertion.

          -  No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning
             treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks must
             have elapsed from any prior surgery, radiation, hormonal or other drug therapy for
             their cancer. Patients must have fully recovered from the acute toxicities of any
             prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities
             (returned to baseline status as noted before most recent treatment). Patients with
             persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.

          -  Any of the following within 6 months prior to first dose of treatment: myocardial
             infarction, symptomatic coronary artery disease (severe or unstable angina), artery
             bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure,
             cerebrovascular accident or transient ischemic attack, or pulmonary embolus.

          -  Known HIV infection. Patients with HIV infection are excluded because there may be
             unknown or dangerous drug interactions between sirolimus/SU11248 (Sutent®) and the
             anti-retroviral agents used to treat HIV infections.

          -  Patients receiving any other standard or investigational treatment for their cancer,
             or any other investigational agent for any indication.

          -  Diagnosis of second malignancy (except malignancies treated with no evidence of
             recurrence for at least 5 years, and curatively treated basal cell or squamous cell
             carcinomas of the skin, or in situ cervical cancer, or any stage I malignancy > 2
             years from treatment).

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, and in
             the judgment of the investigator would make the subject inappropriate for entry into
             this study.

          -  Patients taking concurrent medications of any kind which are strong inducers or
             inhibitors of CYP3A4. Patients receiving any of the following will be excluded:
             ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone,
             nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, dexamethasone,
             phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's
             Wort.