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NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (PrE0801)

This study has been completed.
Information provided by (Responsible Party):
PrECOG, LLC. Identifier:
First received: July 21, 2012
Last updated: September 7, 2016
Last verified: September 2016

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 Intervention Phase
Renal Cell Carcinoma
Drug: Axitinib
Phase 2

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:

Further study details as provided by PrECOG, LLC.:

Primary Outcome Measures:
  • Clinical Benefit [ Time Frame: 36 months ]
    To determine the clinical benefit that retreatment with VEGFR2 TKI therapy confers to patients with recurrent ccRCC after adjuvant treatment.

Secondary Outcome Measures:
  • Response Rate [ Time Frame: 36 months ]
    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 ]
    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 ]
    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 ]
    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.

Enrollment: 3
Study Start Date: July 2012
Study Completion Date: March 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Axitinib
Axitinib will be given orally and will continue until progression of disease.
Drug: Axitinib
Axitinib 5 mg orally with food every 12 hours. One cycle=28 days.
Other Names:
  • AG-013736
  • Tyrosine Kinase Inhibitor (TKI)

Detailed Description:

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Locally recurrent or metastatic RCC requiring systemic therapy following treatment (tx) with sorafenib, sunitinib, pazopanib, or placebo on an adjuvant study
  • Required to have primary or recurrence tumor samples containing clear cell variant RCC with <50% of any other histology
  • Recurrence must occur ≥ 3 months following end of exposure to the adjuvant intervention
  • Received ≥ 3 six week cycles of prior adjuvant tx with sorafenib, sunitinib, pazopanib or placebo in the adjuvant setting on a clinical trial, or recurrence >3 months of tx on an adjuvant placebo arm
  • Required to have measurable recurrent or metastatic disease that is not curable by standard radiation therapy or surgery
  • Male or female, ≥ 18 years old
  • ECOG PS 0 or 1
  • Blood pressure (B/P) must be controlled at time of enrollment. Tx with antihypertensive medication(s) is allowed. Controlled B/P is defined as in clinic measurement of systolic B/P ≤ 140 mm Hg AND diastolic B/P ≤ 90 mm Hg. If B/P is uncontrolled at time of planned enrollment, tx or optimization with antihypertensive medication(s) may be initiated in order to control B/P. Patient may be considered for enrollment when this has happened.
  • Women must not be pregnant or breastfeeding
  • Men and women who are of reproductive potential must be willing to employ an effective method of birth control/contraception
  • Willingness and ability to comply with scheduled visits, tx plans, laboratory tests, and other study procedures
  • Ability to understand and willingness to sign an IRB-approved informed consent
  • Adequate organ function as evidenced by the following, obtained within 28 days prior to registration:

    • Absolute neutrophil count (ANC) ≥ 1250 cells/mm³
    • Platelet count ≥ 75,000 cells/mm³
    • Hemoglobin ≥ 9.0 g/dL
    • Total direct serum bilirubin ≤ 1.5x upper limit of normal (ULN)
    • ALT and AST ≤ 2.5 x ULN unless there are liver metastases in which case AST and ALT ≤ 5.0 x ULN
    • Serum creatinine <1.5 x ULN or calculated creatinine clearance ≥ 45 mL/min
    • Urine protein <2+ by urine dipstick
  • Resolution of all previous tx-related toxicity to ≤ grade 1 or back to baseline
  • No major surgery <4 weeks or radiation therapy <2 weeks of starting study tx. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
  • No clinically significant gastrointestinal abnormalities
  • No current use or anticipated need for tx with drugs that are known potent CYP3A4 inhibitors
  • No current or anticipated need for tx with drugs that are known CYP3A4 or CYP1A2 inducers
  • No current requirement of anticoagulant therapy with oral vitamin K antagonists
  • No untreated brain metastases, spinal cord compression, or carcinomatous meningitis. Patients must be off oral (systemic) steroids prior to registration. Inhalational steroids, e.g., for asthma, emphysema are permissible.
  • No serious uncontrolled medical disorder or active infection that would impair their ability to receive study tx
  • None of the following conditions within the 6 months prior to study drug: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or pulmonary embolism
  • No known HIV or AIDS-related illness
  • No other active malignancy
  • No dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of the protocol
  • No other severe acute/chronic medical or psychiatric condition or lab abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: 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
Sponsors and Collaborators
Study Chair: Stephen Keefe, MD University of Pennsylvania Health System
  More Information

Responsible Party: PrECOG, LLC. Identifier: NCT01649180     History of Changes
Other Study ID Numbers: PrE0801
WS1512227 ( Other Grant/Funding Number: Pfizer )
Study First Received: July 21, 2012
Last Updated: September 7, 2016
Individual Participant Data  
Plan to Share IPD: No
Plan Description: Data is proprietary.

Keywords provided by PrECOG, LLC.:
Clear Cell Renal Cell Carcinoma
Metastatic RCC
Recurrent RCC
Kidney Cancer
Kidney Neoplasms
Tyrosine Kinase Inhibition

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Disease Attributes
Pathologic Processes
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on March 27, 2017