| Conditions: |
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Kidney Cancer |
| Purpose: |
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the
growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such
as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing
the cells or by stopping them from dividing. Giving bevacizumab together with ixabepilone
may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with
ixabepilone works in treating patients with advanced kidney cancer.
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| Study Summary: |
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OBJECTIVES:
Primary
- Determine the objective response rate in patients with advanced renal cell carcinoma
treated with bevacizumab and ixabepilone.
Secondary
- Determine progression-free survival of these patients.
- Characterize the toxicity of bevacizumab and ixabepilone in these patients.
- Determine changes in biomarkers (i.e., tumor tissue biopsy and blood-based proteins,
circulating endothelial cells, and tumor endothelial markers) and correlate with
clinical outcomes in these patients.
OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on day 1 and ixabepilone IV over
1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.
Patients undergo dynamic contrast-enhanced MRI at baseline, after every 2 courses, and after
completion of treatment to correlate changes in biomarkers with clinical outcomes.
Patients undergo biopsies and blood sample collection periodically for biomarker analysis.
Blood samples are analyzed for protein profiling (e.g., VEGF-A, VEGFR-2, VEGFR-3, and βFGF)
by ELISA; tumor endothelial markers (e.g., TEM7s, TEM8s, CD137s, CD276s, and Apelin) by
ELISA; and circulating endothelial cells (e.g., CD31, CD146, CD31, and CD133) by flow
cytometry. Tumor biopsy samples are analyzed for microvessel density, VEGFR-2, VEGFR-3,
HIF1-a, and PDGFR-b levels, and VEGF independent pathway by IHC.
After completion of study treatment, patients are followed every 3 months.
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| Criteria: |
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DISEASE CHARACTERISTICS:
- Pathologically confirmed renal cell carcinoma
- Metastatic or unresectable disease
- Predominant clear cell histology (> 70%)
- Disease progression during or after completion of treatment with a VEGF-receptor
tyrosine kinase inhibitor (e.g., sunitinib malate and/or sorafenib tosylate)
- Primary tissue (as block or unstained slides) required
- Measurable disease by conventional imaging or clinical examination
- No known CNS disease
- Previously treated brain metastases allowed provided there is no ongoing
requirement for steroids AND no evidence of progression or hemorrhage for ≥ 3
months after treatment, as ascertained by clinical examination and brain MRI or
CT scan
- Stable dose of anticonvulsants allowed
- Treatment for brain metastases may have included whole brain radiotherapy,
radiosurgery (e.g., gamma knife, linear accelerator, or equivalent), or a
combination as deemed appropriate by the treating physician
- No symptomatic spinal cord compression
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Hemoglobin ≥ 9.0 g/dL
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 times upper limit of normal (ULN) OR measured creatinine clearance ≥
40 mL/min
- Proteinuria ≤ 500 mg by 24-hour urine collection
- AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver function abnormalities are due to
underlying malignancy)
- Total bilirubin ≤ 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 6 months after the
completion of bevacizumab therapy
- No other invasive malignancies within the past 2 years except non-melanoma skin
cancer, non-invasive bladder cancer, stage I endometrial cancer, or cervical cancer
- No history of uncontrolled or labile hypertension, defined as blood pressure > 160/90
mm Hg on ≥ 2 repeated determinations on separate days within the past 15 days
- No significant traumatic injury within the past 6 weeks
- None of the following conditions within the past 6 months:
- Myocardial infarction, severe/unstable angina pectoris, or coronary/peripheral
artery bypass graft
- New York Heart Association class III-IV congestive heart failure
- Cerebrovascular accident, transient ischemic attack, or other thromboembolic
event
- Peripheral neuropathy ≥ grade 2
- Peptic ulcer disease, erosive esophagitis, or gastritis
- Infectious or inflammatory bowel disease or diverticulitis
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or
recent peripheral arterial thrombosis)
- No evidence of clinically significant bleeding diathesis or underlying coagulopathy
- No severe acute or chronic medical or psychiatric condition or significant laboratory
abnormality requiring further investigation that, in the judgment of the
investigator, may cause undue safety risk, inhibit study participation, or interfere
with interpretation of study results
- No serious or non-healing wound, ulcer, or bone fracture
- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered to NCI CTCAE grade ≤ 1 toxicity from any prior therapy (except alopecia)
- More than 3 months since prior neurosurgical resection or brain biopsy for CNS
metastases
- More than 6 weeks since prior and no concurrent major surgical procedure or open
biopsy
- More than 2 weeks since prior minor surgery (e.g., port-a-cath placement or dental
procedures)
- At least 4 weeks since other prior therapy
- No prior cumulative radiotherapy to > 25% of the total bone marrow
- No prior bevacizumab or ixabepilone
- Prior aldesleukin, interferon, and/or mTOR treatment allowed
- No concurrent antiretroviral therapy for HIV-positive patients
- No concurrent radiotherapy
- No concurrent CYP3A4 inhibitors
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| NCT ID: |
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NCT00820209 |
| Primary Contact: |
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Principal Investigator
Antonio T. Fojo, MD, PhD
National Cancer Institute (NCI)
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937
Site Status: Recruiting |