NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (PrE0801)
The purpose of this study is to see how well the study drug, axitinib, helps control renal (kidney) cancer that has come back (recurrent) or spread (metastatic). Patients must have already been treated as a participant in a clinical trial with sunitinib, sorafenib, or placebo (sugar pill) after their initial surgery.
This study will examine the effect of adjuvant tyrosine kinase inhibition (TKI) therapy (sorafenib or sunitinib) on subsequent exposure to TKI with axitinib in the first-line recurrent or metastatic setting.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition (TKI) at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (RCC)|
- Clinical Benefit [ Time Frame: 36 months ] [ Designated as safety issue: No ]To determine the clinical benefit that retreatment with VEGFR2 TKI therapy confers to patients with recurrent ccRCC after adjuvant treatment.
- Response Rate [ Time Frame: 36 months ] [ Designated as safety issue: No ]To determine the overall response rate to the aforementioned TKI therapeutic in recurrent disease associated with post-adjuvant TKI therapy.
- Biospecimen Banking for IL-8 and VEGF-A [ Time Frame: 24 months ] [ Designated as safety issue: No ]To bank biospecimens for the retrospective determination of whether baseline or changes in cytokine levels of IL-8 and VEGF-A predict response to treatment in this setting. Banking of plasma and serum is optional but strongly encouraged.
- Biospecimen Banking for SNPs analysis [ Time Frame: 24 months ] [ Designated as safety issue: No ]To bank biospecimens for the retrospective determination of whether baseline single nucleotide polymorphisms (SNPs) in angiogenesis-related genes predict response to treatment (candidate gene approach). Banking of PBMC is optional but strongly encouraged.
- Bank Tumor Tissue [ Time Frame: 24 months ] [ Designated as safety issue: No ]To bank tumor tissue (formalin-fixed, paraffin-embedded tumor blocks) for retrospective examination of the molecular pathophysiologic mediators of tumorigenesis and progression such as phospho-protein expression of MAPK signaling network intermediates in endothelial cells. Banking of tumor tissue is optional but strongly encouraged.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||November 2015|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Axitinib will be given orally and will continue until progression of disease.
Axitinib 5 mg orally with food every 12 hours. One cycle=28 days.
Approximately 60,920 cases of cancer involving the kidney and renal pelvis were diagnosed in the United States in 2010 and 13,120 deaths occurred from these tumors. The rate of Renal Cell Carcinoma (RCC) has increased by 2% per year for the past 65 years. The reason for this increase in unknown but smoking and obesity are risk factors for the development of RCC. Early stage disease is typically treated with resection with definitive intent with partial or radical nephrectomy. Patients with metastatic disease are often treated with systemic therapy with palliative intent. Systemic therapeutic options include so-called targeted therapies, and less often chemotherapy and immunomodulatory therapies (interferon alpha and interleukin-2).
The Food and Drug Administration (FDA) has approved six targeted agents for the treatment of advanced and metastatic renal cell carcinoma that fall into two general classes - vascular endothelial growth factor (VEGF) inhibitors and inhibitors of mammalian target of rapamycin (mTOR). On the basis of several randomized phase III studies, vascular endothelial growth factor receptor-2 (VEGFR2) inhibitor therapy has become the generally preferred treatment for recurrent and metastatic ccRCC (clear cell Renal Cell Carcinoma) in the first-line setting. Treatment of ccRCC with VEGF-inhibition in the first-line metastatic setting, is associated with a progression-free survival of approximately 11 months. Vascular endothelial growth factor (VEGF) inhibitor therapy in the second-line remains active, but to a lesser degree - progression-free survival (PFS) has been reported to be between 5 and 7 months.
Adjuvant treatment of high-risk, early-stage ccRCC with VEGFR2 TKI therapy following definitive resection has become an area of active investigation. The ASSURE trial (ECOG 2805) recently completed accrual, and other adjuvant trials - i.) SORCE (sorafenib for 3 or 1 year versus placebo), ii.) S-Trac (sunitinib versus placebo) - are in accrual.
Axitinib (AG-013736, Pfizer Inc.), a receptor-tyrosine kinase inhibitor that is selective for VEGFR1, 2, and 3, is an important new agent for use in metastatic RCC. Axitinib has been examined extensively in RCC, and it has been shown to be safe, well-tolerated, and highly active. On January 27, 2012, the FDA approved axitinib for the treatment of advanced RCC after failure of one prior systemic therapy.
|Contact: Steven Adler, RNemail@example.com|
|Contact: Carolyn Andrews, RNfirstname.lastname@example.org|
|United States, Alabama|
|University of Alabama at Birmingham||Recruiting|
|Birmingham, Alabama, United States, 35294|
|Contact: Sharon Barkley, RN 205-975-2008 email@example.com|
|Principal Investigator: Carla Falkson, MD|
|United States, Illinois|
|Loyola University of Chicago, Cardinal Bernardin Cancer Center||Recruiting|
|Maywood, Illinois, United States, 60153|
|Contact: Ann Clark, RN, MSN 708-327-3221 firstname.lastname@example.org|
|Principal Investigator: Joseph I Clark, MD|
|United States, Kansas|
|Cancer Center of Kansas||Recruiting|
|Wichita, Kansas, United States, 67214|
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|Principal Investigator: Shaker R Dakhil, MD|
|United States, Nebraska|
|Missouri Valley Cancer Consortium||Recruiting|
|Omaha, Nebraska, United States, 68106|
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|Principal Investigator: Gamini Soori, MD|
|United States, Ohio|
|Cleveland Clinic, Taussig Cancer Institute||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Laura Wood, RN, MSN 216-444-9822 email@example.com|
|Principal Investigator: Brian I Rini, MD|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111|
|Contact: Lois Malizzia, RN, CCRP 215-728-5311 firstname.lastname@example.org|
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|Philadelphia, Pennsylvania, United States, 19104|
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|Principal Investigator: Leonard Appleman, MD, PhD|
|Study Chair:||Stephen Keefe, MD||University of Pennsylvania Health System|