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

NCT01649180 | Terminated Phase 2 Results DMC

• 2 other identifiers: PrE0801WS1512227
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Renal Cell Carcinoma

Keywords

RCC; Clear Cell Renal Cell Carcinoma; ccRCC; Metastatic RCC; Recurrent RCC; Kidney Cancer; Kidney Neoplasms; Axitinib; AG-013736; Tyrosine Kinase Inhibition; TKI

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  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.

  Assessed every 12 weeks up to 36 months

Secondary Outcomes (4)

• Overall Response Rate

  Assessed every 12 weeks up to 36 months

• Biospecimen Banking for IL-8 and VEGF-A

  Baseline and 8 weeks

• Biospecimen Banking for SNPs Analysis

  Baseline

• Tumor Tissue Banking

  Baseline

Study Arms (1)

Axitinib

EXPERIMENTAL

Axitinib will be given orally and will continue until progression of disease.

Drug: Axitinib

Interventions

Axitinib DRUG

Axitinib 5 mg orally with food every 12 hours. One cycle=28 days.

Also known as: AG-013736, Tyrosine Kinase Inhibitor (TKI)

Axitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• PrECOG, LLC.: lead
• Pfizer: collaborator

Study Sites (3)

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Cleveland Clinic, Taussig Cancer Institute

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (4)

• Rini BI, Wilding G, Hudes G, Stadler WM, Kim S, Tarazi J, Rosbrook B, Trask PC, Wood L, Dutcher JP. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol. 2009 Sep 20;27(27):4462-8. doi: 10.1200/JCO.2008.21.7034. Epub 2009 Aug 3.

  PMID: 19652060 BACKGROUND

• Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY, McTigue MA, Murray BW, Kania RS, O'Connor P, Shalinsky DR, Bender SL. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83. doi: 10.1158/1078-0432.CCR-08-0652.

  PMID: 19010843 BACKGROUND

• Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J, Trask PC, Kim S, Rini BI. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007 Nov;8(11):975-84. doi: 10.1016/S1470-2045(07)70285-1. Epub 2007 Oct 23.

  PMID: 17959415 BACKGROUND

• Escudier B, Gore M. Axitinib for the management of metastatic renal cell carcinoma. Drugs R D. 2011;11(2):113-26. doi: 10.2165/11591240-000000000-00000.

  PMID: 21679004 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Axitinib; Tyrosine Kinase Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: PrECOG Statistician
• Organization: ECOG-ACRIN Biostatistics Center

jmanola@jimmy.harvard.edu

617-632-3633

Study Officials

• Stephen Keefe, MD

  University of Pennsylvania Health System

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2012
• First Posted: July 25, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: March 1, 2016
• Last Updated: August 12, 2021
• Results First Posted: April 20, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)