There are two drugs involved in this study. Sunitinib (Sutent(R)) is approved by the Food
and Drug Administration (FDA) for the treatment of advanced renal cell (kidney) cancer and
gastrointestinal stromal tumors. Sunitinib is thought to work by blocking the growth of
blood vessels into tumors; reducing the blood supply to tumors can slow their growth and
sometimes causes the tumors to shrink. Sirolimus has been approved by the FDA to prevent the
body from rejecting organ transplants. Sirolimus is being tested for its effects against
cancer because it can slow the growth of some tumors in animal models. Sirolimus is thought
to slow cancer growth in these animal models both by direct effects on the tumor cells, and
also by blocking production of growth factors that stimulate production of blood vessels. We
hope that the combined use of these two drugs will have better anti-cancer effects than
either agent alone. This study is designed to find out if different doses of Sirolimus
combined with a standard dose of Sutent are safe and well tolerated. Additionally, it is
hoped to gain knowledge about the way that Sutent(R) in combination with sirolimus affects
the blood vessels produced by cancer.
Minimum age: 18 Years.
Maximum age: N/A.
- 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
- 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
- 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
- Any ongoing coagulopathies or receiving anticoagulants.
- Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal
- 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
- 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