Alternating Targeted Therapy in Patients With Metastatic Renal Cell Carcinoma: A Phase II Study of Alternating Sunitinib and Temsirolimus
- Histologically confirmed metastatic renal cell cancer with evaluable disease.
- Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery
or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.
- Karnofsky Performance Status ≥60%
- Life expectancy ≥ twelve weeks
- Adequate end organ function:
Cardiac Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal
(LLN) as assessed by echocardiography or multigated acquisition (MUGA) scan. The same
modality used at baseline must be applied for subsequent evaluations.
- Women should not be lactating and, if of childbearing age, have a negative pregnancy
test within two weeks of entry to the study and practicing acceptable forms of birth
- Appropriate Contraception in both sexes
- The patient must be competent and signed informed consent.
- Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive
cancer such as cervical CIS, superficial bladder cancer without local recurrence,
- In patients with a prior history of invasive malignancy, less than five years in
- Have evidence of significant co-morbid illness such as uncontrolled diabetes,
hypertension or active infection that would preclude treatment on this regimen.
- Use of corticosteroids or other immunosuppression (if patient had been taking
steroids, at least 4 weeks must have passed since the last dose).
- Prior treatment with either sunitinib or temsirolimus
- Clinically significant gastrointestinal abnormalities
- Presence of uncontrolled infection.
- Prolongation of corrected QT interval (QTc) > 480 milliseconds - History of any one
or more of the following cardiovascular conditions within the past 12 months:
1. Cardiac angioplasty or stenting
2. Myocardial infarction
3. Unstable angina
4. Coronary artery by-pass graft surgery
5. Symptomatic peripheral vascular disease
6. Class III or IV congestive heart failure, as defined by the New York Heart
- History of cerebrovascular accident (CVA) including transient ischemic attack
(TIA) within the past 12 months.
- History of pulmonary embolism or untreated deep venous thrombosis (DVT)within the
past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic
anticoagulating agents for at least 6 weeks are eligible.
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of
≥150 or diastolic blood pressure (DBP) of ≥ 90. Note: Initiation or adjustment of
antihypertensive medication(s) is permitted prior to study entry.
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer.
- Evidence of active bleeding or bleeding diathesis
- Hemoptysis within 6 weeks of first dose of study drug.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
that could interfere with subject's safety, obtaining informed consent or compliance
to the study.
- Is now undergoing and/or has undergone in the 14 days immediately prior to first dose
of study drug any minor surgeries (i.e. skin biopsy, tooth extraction, etc.) and
recovered from all ill effects.
- Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity.
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to sunitinib or temsirolimus.
- Untreated brain metastasis. (Brain metastases that are stable based on radiographic
evidence 4 weeks after radiation and/or surgery are permitted).