NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (PrE0801)
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|ClinicalTrials.gov Identifier: NCT01649180|
Recruitment Status : Terminated (Closed due to prolonged enrollment timelines)
First Posted : July 25, 2012
Results First Posted : April 20, 2017
Last Update Posted : May 23, 2017
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, pazopanib or placebo (sugar pill) after their initial surgery.
This study will examine the effect of adjuvant tyrosine kinase inhibition (TKI) therapy (sorafenib, sunitinib or pazopanib) on subsequent exposure to TKI with axitinib in the first-line recurrent or metastatic setting.
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Drug: Axitinib||Phase 2|
Approximately 64,770 cases of cancer involving the kidney and renal pelvis were diagnosed in the United States in 2012 and 13,570 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition (TKI) at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (RCC)|
|Study Start Date :||July 2012|
|Primary Completion Date :||January 2016|
|Study Completion Date :||March 2016|
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.
- Progression-free Survival [ Time Frame: Assessed every 12 weeks up to 36 months ]Progression-free survival is defined as the time from registration to disease progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
- Overall Response Rate [ Time Frame: Assessed every 12 weeks up to 36 months ]
Best overall response was evaluated using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0). Response is defined as complete response or partial response.
Complete Response (CR): disappearance of all target lesions Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions
- Biospecimen Banking for IL-8 and VEGF-A [ Time Frame: Baseline and 8 weeks ]
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.
Note: The assays to assess cytokine levels of IL-8 and VEGF-A were not performed because the study stopped early and only 3 patients were enrolled. Therefore, the analysis to evaluate the associations between response and IL-8 as well as VEGF-A was not be done.
- Biospecimen Banking for SNPs Analysis [ Time Frame: Baseline ]
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.
Note: The SNP genotyping analysis was not performed because the study stopped early and only 3 patients were enrolled. Therefore, the analysis to evaluate the association between baseline SNPs in angiogenesis-related genes and response was not be done.
- Tumor Tissue Banking [ Time Frame: Baseline ]
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.
Note: None of the 3 patients submitted tumor tissues so the analysis won't be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01649180
|United States, Nebraska|
|Missouri Valley Cancer Consortium|
|Omaha, Nebraska, United States, 68106|
|United States, Ohio|
|Cleveland Clinic, Taussig Cancer Institute|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania, Abramson Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||Stephen Keefe, MD||University of Pennsylvania Health System|