The purpose of this study is to test the hypothesis that the combination of gemcitabine and
doxil will have clinical activity in patients with metastatic renal cell carcinoma.
Patients with metastatic renal cell carcinoma who have received prior therapy with
sorafenib, sunitinib or temisolimus and have progressive disease may participate in this
study if all eligibility criteria are met. Doxil will be administered on day 1 and
gemcitabine on day 1 and 8 of a 21 day cycle. Tumor responses will be evaluated by RECIST.
Up to six cycles of study treatment may be administered. Cardiac ejection fraction will be
- Patients with renal cell carcinoma who have had disease progression through
sorafenib, sunitinib, or temsirolimus (within 6 months of treatment).
- Diagnosis of RCC has been confirmed by pathological or cytological examination of
tissue obtained from the primary tumor or a metastatic site.
- Clear cell and non-clear cell histological variants are permitted.
- With the exception of prior gemcitabine or any anthracycline (e.g., doxorubicin,
epirubicin, DOXIL), any number of prior therapies with are permited.
- Prior nephrectomy is permitted but not required for eligibility.
- Patients who have received palliative radiation therapy (XRT) to any area other than
the brain (see below) may begin therapy immediately after completion of XRT as long
as the irradiated lesion(s) is/are not used for clinical response assessment.
- Patients requiring XRT or gamma-knife (or similar) therapy to the brain must wait at
least 4 weeks after the completion of irradiation before starting therapy.
- Only patients with either stable or regressing brain metastases after irradiation, as
determined by CT or MRI, are eligible for therapy.
- No systemic therapy within 28 days prior to enrollment except as below:
- No sorafenib, sunitinib, temsirolimus therapy within 14 days prior to
- Toxicities from prior therapy must have resolved to ≤Grade I.
- Survival: anticipated survival of at least three months.
- Renal function: creatinine ≥ 2.0 mg/dL.
- Patients must have a MUGA scan or 2-D echocardiogram indicating an ejection fraction
of ≥50% within 42 days prior to the first dose of study drug. The method used at
baseline must be used for later monitoring.
- Prior to each new cycle of therapy: hepatic function: AST, ALT ≥ 3X the upper limit
of normal, unless the liver is involved by tumor, in which case the transaminases
must be ≥ 5X the upper limit of normal. Total bilirubin must be ≥ 1.5 mg/dL.
- Prior to each new cycle of therapy: bone marrow function: absolute neutrophil count
(ANC) ≥ 1,500; platelet count ≥ 100,000; hemoglobin ≥ 10 g/dL.
- Performance status: ECOG 0 or 1.
- Age: ≥ 18 years.
- Signed informed consent must be obtained from participating individuals.
- Patients with reproductive potential must use an adequate contraceptive method (e.g.,
abstinence, intrauterine device, oral contraceptives, barrier device with spermicide,
or surgical sterilization) during treatment and for three months after completing
treatment. If a patient becomes pregnant while on study, the patient will be removed
from the study and all drug treatment discontinued.
- Patients who have received prior therapy with gemcitabine or an anthracycline drug
(e.g., doxorubicin, epirubicin, DOXIL).
- Patients with untreated central nervous system metastases.
- Patients with active bacterial or fungal infections.
- Patients with psychiatric disorders that would interfere with consent, compliance
with protocol requirements, or follow-up.
- Patients with a history of prior malignancy other than RCC, except for adequately
treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other
cancer for which the patient has been disease-free for 5 years.
- Patients with any other severe concurrent disease, which, in the judgment of the
investigator, would make the patient inappropriate for the entry into the study.
- Pregnant or lactating women.
- History of hypersensitivity reactions attributed to a conventional formulation of
doxorubicin HCL or the component of DOXIL,
- History of cardiac disease with New York Heart Association Class II or greater
cardiac function or clinical evidence of congestive heart failure.