A Study of Tivozanib (AV-951), an Oral VEGF Receptor Tyrosine Kinase Inhibitor, in the Treatment of Renal Cell Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00502307
First received: July 16, 2007
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

This phase 2 trial is evaluating the antineoplastic activity of tivozanib (AV-951) in treating patients with recurrent or metastatic renal cell cancer. Tivozanib (AV-951) is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor.


Condition Intervention Phase
Carcinoma, Renal Cell
Drug: Tivozanib (AV-951)
Drug: Placebo comparator
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Placebo-Controlled, Randomized, Discontinuation Trial of Tivozanib (AV-951) in Patients With Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by AVEO Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To determine the safety of tivozanib (AV-951) with this dose schedule [ Time Frame: 28 weeks after study entry ] [ Designated as safety issue: Yes ]
  • To determine objective response (CR + PR) rate at 16 weeks [ Time Frame: 16 weeks after study entry ] [ Designated as safety issue: No ]
  • To determine the percentage of randomly assigned patients remaining progression free at 12 weeks following random assignment to tivozanib (AV-951) or placebo [ Time Frame: 28 weeks after study entry ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the progression free-survival after random assignment (randomized sub-set only) [ Time Frame: 28 weeks from study entry ] [ Designated as safety issue: No ]
  • Overall progression-free survival (from start of treatment) [ Time Frame: 12 months from study entry ] [ Designated as safety issue: No ]
  • Characterization of pharmacokinetic and pharmacodynamic (PD) profiles of tivozanib (AV-951) in a subset of patients [ Time Frame: 28 weeks from study entry ] [ Designated as safety issue: No ]

Enrollment: 272
Study Start Date: October 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Tivozanib (AV-951) administered as a solid dosage form daily for three weeks per month
Drug: Tivozanib (AV-951)
solid oral dosage form taken daily for three weeks per one month cycle
Placebo Comparator: 2
solid oral capsule containing excipients dosed daily for three weeks per month
Drug: Placebo comparator
solid oral capsule containing excipients dosed daily for three weeks per month

Detailed Description:

Approximately 200 patients will be enroled into the initial, 16 week, open-label period using 1.5 mg/day dosing. Patients will receive tivozanib (AV-951) continuously for 3 weeks followed by 1 week off study drug. Patients will undergo disease assessment at baseline and after Cycles 2 and 4 and response will be determined by RESIST criteria.

After the initial, 16 week open-label period, disease status will be assessed and compared to baseline using modified RECIST criteria:

  • Patients with greater than or equal to 25% tumor shrinkage will continue on their current dose of tivozanib (AV-951)
  • Patients with less than 25% tumor change (growth or shrinkage) will be randomly assigned to double-blind tivozanib (AV-951) or matching placebo for 12 weeks
  • Patients with greater than or equal to 25% tumor growth will be discontinued
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 year old males or females
  • Patients with recurrent or metastatic renal cell carcinoma (RCC) or primary RCC that is not amendable to surgical intervention
  • Histologically or cytologically confirmed renal cell carcinoma
  • Measurable disease
  • No more than one prior systemic treatment (chemotherapy or immunotherapy) for RCC.
  • No active brain metastases
  • Karnofsky performance status ≥ 70%, life expectancy ≥ 3 months
  • No childbearing potential, or use of effective contraception during the study and for 4 weeks after the last dose of study drug
  • Archival paraffin embedded tumor tissue, if available.
  • Ability to give written informed consent

Exclusion Criteria:

  • Pregnant or lactating women
  • Primary CNS malignancies; active CNS metastases
  • Hematologic malignancies (includes: leukemia, any form; lymphoma; and multiple myeloma)
  • Any of the following hematologic abnormalities:

    • Hemoglobin ≤ 9.0 g/dL
    • ANC < 1500 per mm3
    • Platelet count < 100,000 per mm3
  • Any of the following serum chemistry abnormalities:

    • Total bilirubin > 1.5 × the ULN
    • AST or ALT ≥ 2.5 × the ULN
    • Serum albumin < 3.0 g/dL
    • Creatinine > 1.7 × ULN (or calculated CLCR <50 mL/min/1.73 m2)
    • Proteinuria > 2.5 g/24 hours or 4+ with urine dipstick
  • Significant cardiovascular disease, including:

    • Active clinically symptomatic left ventricular failure
    • Active HTN (diastolic blood pressure > 100 mmHg). Patients with a history of hypertension must have been on stable doses of anti-hypertensive drugs for ≥ 4 weeks
    • Uncontrolled hypertension: Blood pressure >140/90 mmHg on more than 2 antihypertensive medications.
    • Myocardial infarction within 3 months prior to administration of first study dose
  • Unhealed wounds (including active gastric ulcers)
  • Serious/active infection; infection requiring parenteral antibiotics
  • Inadequate recovery from prior antineoplastic therapy
  • Inadequate recovery from any prior surgical procedure; major surgical procedure within 4 weeks prior to study entry
  • Life-threatening illness or organ system dysfunction compromising safety evaluation
  • Psychiatric disorder, altered mental status precluding informed consent or necessary testing
  • Inability to comply with protocol requirements
  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 ClinicalTrials.gov identifier: NCT00502307

Locations
India
Vellore, Tamil Nadu, India, 632004
Kolkata, India
Mumbai, India
New Delhi, India
Pune, India
Russian Federation
Astrakhan, Russian Federation
Ioshkar-Ola, Russian Federation
Kazan, Russian Federation
Moscow, Russian Federation, 129128
Moscow, Russian Federation, 125284
Moscow, Russian Federation
Novgorod, Russian Federation
Obninsk, Russian Federation
Pyatigorsk, Russian Federation
Rostove-on-Don, Russian Federation
Sochi, Russian Federation
St. Petersburg, Russian Federation
Tomsk, Russian Federation
Ufa, Russian Federation
Ukraine
Cherkassy, Ukraine
Dnepropetrovsk, Ukraine
Donetsk, Ukraine
Kharkov, Ukraine
Lviv, Ukraine
Uzhgorod, Ukraine
Zaporizzhya, Ukraine
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
Investigators
Principal Investigator: Dmitriy G Nosov, M.D. Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences
  More Information

No publications provided

Responsible Party: AVEO Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00502307     History of Changes
Other Study ID Numbers: AV-951-07-201
Study First Received: July 16, 2007
Last Updated: October 2, 2012
Health Authority: United States: Food and Drug Administration
Russia: Ukraine: India

Keywords provided by AVEO Pharmaceuticals, Inc.:
Renal Cell Carcinoma
AV-951
tivozanib

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 22, 2014