A Biomarker Study of Tivozanib in Subjects With Advanced Renal Cell Carcinoma

NCT01297244 | Completed Phase 2 Results

• 1 other identifier: AV-951-10-202
• Study Type: interventional
• Target: 105
• Locations: 2 countries
• Sites: 25

Brief Summary

This is an open-label, single arm, multicenter study. Subjects will be stratified by histology (clear cell versus non-clear cell). Enrollment of non-clear cell subjects will be limited to ≤ 30% of the entire study population.

Conditions

Renal Cell Carcinoma

Keywords

AV-951; Tivozanib; RCC; Biomarkers; Advanced Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Biomarkers in Blood and Archived Tissue Samples, and Their Correlation With Clinical Activity in Subjects With Advanced Renal Cell Cancer Treated With Tivozanib.

  To Evaluate CD68, HIF (hypoxia induced factor) 1/HIF2, VEGF A, VEGF-B, VEGF-C, VEGF-D, HGF (hepatocyte growth factor), CAIX, and PLGF (placental growth factor) levels and a biomarker signature based on transcriptional profiles.

  Cycle 1 day 1, cycle 1 day 15 and cycle 2 day 1.

• Biomarkers in Blood and Archived Tissue Samples, and Their Correlation With Treatment-related Toxicity in Subjects With Advanced Renal Cell Cancer Treated With Tivozanib.

  To Evaluate biomarkers like VEGF-A, VEGF-B, VEGF-C, VEGF-D, HGF, and PLGF levels, protein expression and metabolite patterns.

  Cycle 1 day 1, cycle 1 day 15 and cycle 2 day 1.

• Number of Tivozanib-treated Subjects Who Are Progression-free at 6 Months

  Subjects were considered to be progression-free at 6 months if they did not have disease progression or death by Day 182 and if they had an evaluation of confirmed PR, unconfirmed PR, or SD on or after Day 144.

  Throughout the treatment period (approximately 6 months from the subject's first dose of tivozanib).

Secondary Outcomes (3)

• Number of Subjects With Objective Response Rate (ORR)

  Throughout the treatment period (approximately 6 months from the subject's first dose of tivozanib).

• Kaplan-Meier Estimate of Progression-free Survival (PFS)

  Throughout the treatment period (approximately 6 months from the subject's first dose of tivozanib).

• Number of Subjects With Adverse Events

  Throughout the treatment period (approximately 6 months from the subject's first dose of tivozanib) and 30 day follow-up period.

Study Arms (1)

Tivozanib

EXPERIMENTAL

Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

Drug: Tivozanib

Interventions

Tivozanib DRUG

Subjects will receive 1.5 mg tivozanib once daily beginning on Day 1 for 3 weeks followed by 1 week off treatment. One cycle will be defined as 4 weeks of treatment. Cycles will be repeated every 4 weeks.

Tivozanib

Eligibility Criteria

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

You may qualify if:

• ≥ 18 year old males or females
• Subjects with unresectable locally recurrent or metastatic renal cell carcinoma (RCC)
• Histologically or cytologically confirmed clear cell renal cell carcinoma (≥ 50% clear cell) or non-clear cell RCC (all histologies)
• Subjects must have undergone prior nephrectomy (complete or partial) for excision of the primary tumor.
• Measurable disease per RECIST criteria Version 1.1 (see Appendix A)
• Treatment naïve subjects or subjects who have received no more than one prior systemic treatment (immunotherapy, including interferon-alfa or interleukin-2 based therapy, chemotherapy, hormonal therapy or an investigational agent) for metastatic RCC.
• Eastern Cooperative Oncology Group performance status of 0 or 1, and life expectancy ≥ 3 months
• If female and of childbearing potential, documentation of negative pregnancy test prior to enrollment
• Willingness to provide archival paraffin embedded tumor tissue, if available.
• Ability to give written informed consent and comply with protocol requirements

You may not qualify if:

• Any prior vascular endothelial growth factor (VEGF)-directed therapy including VEGF antibody (eg, bevacizumab), VEGF receptor tyrosine kinase inhibitor (eg, sunitinib, sorafenib, axitinib, pazopanib, etc.), VEGF trap (eg, aflibercept), or any other agent or investigational agent targeting the VEGF pathway.
• Any prior therapy with an agent targeting the mechanistic target of rapamycin pathway (eg, temsirolimus, everolimus, etc)
• Primary central nervous system (CNS) malignancies or CNS metastases; subjects with previously treated brain metastasis will be allowed if the brain metastasis have been stable without steroid treatment for at least 3 months following prior treatment (radiotherapy or surgery).
• Any of the following hematologic abnormalities:
• Hemoglobin \< 9.0 g/dL
• Absolute neutrophil count (ANC) \< 1500 per mm3
• Platelet count \< 100,000 per mm3
• International Normalized Ratio \>1.5 or partial thromboplastin time \>1.5 × upper limit of normal (ULN)
• Any of the following serum chemistry abnormalities:
• Total bilirubin \> 1.5 × ULN (or \> 2.5 × ULN for subjects with Gilbert's syndrome)
• Aspartate aminotransferase or alanine aminotransferase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver metastasis)
• Alkaline phosphatase \> 2.5 × ULN (or \> 5 × ULN for subjects with liver or bone metastasis)
• Creatinine \> 2.0 × ULN
• Proteinuria \> 3+ by urinalysis or urine dipstick
• Significant cardiovascular disease, including:

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (25)

Southern Cancer Center

Mobile, Alabama, United States

Location

Providence Health and Services

Burbank, California, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, United States

Location

St. Francis Cancer Research Foundation

Beech Grove, Indiana, United States

Location

Cancer Center of Kansas

Wichita, Kansas, United States

Location

Medical Oncology, LLC

Baton Rouge, Louisiana, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

Cancer & Hematology Centers of Western Michigan

Grand Rapids, Michigan, United States

Location

North Mississippi Hematology & Oncology Associates, Ltd.

Tupelo, Mississippi, United States

Location

Comprehensive Cancer Centers of Nevada & US Oncology Research

Las Vegas, Nevada, United States

Location

Mary Hitchcock Memorial Hospital, NH

Lebanon, New Hampshire, United States

Location

University of North Carolina, Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Location

Ohio State University

Columbus, Ohio, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Location

The Jones Clinic

Germantown, Tennessee, United States

Location

The West Clinic

Memphis, Tennessee, United States

Location

Texas Oncology-Austin North

Austin, Texas, United States

Location

Coastal Bend Cancer Center

Corpus Christi, Texas, 78404, United States

Location

Texas Oncology-Baylor, Charles A. Sammons Cancer Center

Dallas, Texas, United States

Location

BC Cancer Agency Vancouver Centre

Vancouver, British Columbia, Canada

Location

Juravinski Cancer Center

Hamilton, Ontario, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Sunnybrook Odette Cancer Center, Toronto

Toronto, Ontario, Canada

Location

Montreal General Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

tivozanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney 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

Limitations and Caveats

The primary efficacy analyses of correlations between biomarkers in blood and archived tissue and PFS and objective response were not completed due to voluntary study discontinuation.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: AVEO Pharmaceuticals, Inc.

Clinical@aveooncology.com

857-400-0101

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 16, 2011
• Study Start: January 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 27, 2020
• Results First Posted: October 27, 2020

Record last verified: 2020-10

Locations

US (20); CA (5)