NCT00502307

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
272

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2007

Typical duration for phase_2

Geographic Reach
3 countries

26 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 16, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 17, 2007

Completed
3 months until next milestone

Study Start

First participant enrolled

October 1, 2007

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2010

Completed
10.1 years until next milestone

Results Posted

Study results publicly available

September 1, 2020

Completed
Last Updated

September 1, 2020

Status Verified

August 1, 2020

Enrollment Period

2.8 years

First QC Date

July 16, 2007

Results QC Date

July 6, 2020

Last Update Submit

August 17, 2020

Conditions

Carcinoma, Renal Cell

Keywords

Renal Cell CarcinomaAV-951tivozanib

Outcome Measures

Primary Outcomes (3)

  • Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs)

    To determine the safety and tolerability of tivozanib (AV-951) with the protocol-specified dose schedule

    28 weeks after study entry

  • Objective Response [Complete Response (CR) + Partial Response (PR)] Rate at 16 Week Open-Label Period (All Treated Population)

    The ORR is defined as the rate of (CR+PR). Objective response rates following the 16-week, open-label period (investigator assessment and IRR assessment) were estimated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and was assessed by magnetic resonance imaging (MRI): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response (OR) = CR + PR.

    16 weeks after study entry

  • Percentage of Randomly Assigned Subjects Remaining Progression Free at 12 Weeks Following Random Assignment to Tivozanib (AV-951) or Placebo

    Percentages of subjects remaining progression-free at 12 weeks post-randomization were compared across the 2 treatment arms in the ITT population. A Cochran-Mantel- Haenszel (CMH) test of general association was used, stratifying by country to evaluate the null hypothesis that treatment arm is not associated with subjects remaining progression-free. Non-completers were treated as failures. Progression is defined using 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.

    28 weeks after study entry

Secondary Outcomes (5)

  • Number of Subjects With Progression Free-survival (PFS) After Random Assignment (Randomized Sub-set Only) (at 12 Weeks Post Randomization )

    28 weeks from study entry

  • Overall Progression-free Survival (From Start of Treatment)

    12 months from study entry

  • Time to Peak Plasma Concentration (Tmax) of Tivozanib in a Subset of Subjects

    Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose

  • Maximum Observed Serum Concentration During a Dosing Interval at Steady State (Cmax)

    Cycle 1, Day 1: Pre-dose and 2, 4 and 24 hours post dose; Cycle 1, Day 8: Pre-dose; Cycle 1, Day 21: Pre-dose and 2, 4, 24, 48, and 96 hours post dose; Cycle 2 (Day 1): Pre-dose

  • Area Under the Serum Concentration Versus Time Curve From Zero to the Last Quantifiable Sampling Point [AUC(0→24)]

    28 weeks from study entry

Study Arms (2)

1

EXPERIMENTAL

Tivozanib (AV-951) administered as a solid dosage form daily for three weeks per month

Drug: Tivozanib (AV-951)

2

PLACEBO COMPARATOR

solid oral capsule containing excipients dosed daily for three weeks per month

Drug: Placebo comparator

Interventions

Tivozanib (AV-951)DRUG

solid oral dosage form taken daily for three weeks per one month cycle

1
Placebo comparatorDRUG

solid oral capsule containing excipients dosed daily for three weeks per month

2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ≥ 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

You may not qualify if:

  • 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
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

Unknown Facility

Vellore, Tamil Nadu, 632004, India

Location

Unknown Facility

Kolkata, India

Location

Unknown Facility

Mumbai, India

Location

Unknown Facility

New Delhi, India

Location

Unknown Facility

Pune, India

Location

Unknown Facility

Astrakhan, Russia

Location

Unknown Facility

Kazan', Russia

Location

Unknown Facility

Moscow, 125284, Russia

Location

Unknown Facility

Moscow, 129128, Russia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Obninsk, Russia

Location

Unknown Facility

Pyatigorsk, Russia

Location

Unknown Facility

Rostove-on-Don, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Sochi, Russia

Location

Unknown Facility

Tomsk, Russia

Location

Unknown Facility

Ufa, Russia

Location

Unknown Facility

Veliky Novgorod, Russia

Location

Unknown Facility

Yoshkar-Ola, Russia

Location

Unknown Facility

Cherkassy, Ukraine

Location

Unknown Facility

Dnipro, Ukraine

Location

Unknown Facility

Donetsk, Ukraine

Location

Unknown Facility

Kharkiv, Ukraine

Location

Unknown Facility

Lviv, Ukraine

Location

Unknown Facility

Uzhhorod, Ukraine

Location

Unknown Facility

Zaporizzhya, Ukraine

Location

Related Publications (1)

  • Barata PC, Chehrazi-Raffle A, Allman KD, Asnis-Alibozek A, Kasturi V, Pal SK. Activity of Tivozanib in Non-clear Cell Renal Cell Carcinoma: Subgroup Analysis From a Phase II Randomized Discontinuation Trial. Oncologist. 2023 Oct 3;28(10):894-900. doi: 10.1093/oncolo/oyad132.

    PMID: 37315114DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

tivozanib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Chief Medical Officer
Organization
AVEO Pharmaceuticals, Inc.
Clinical@aveooncology.com
857-400-0101

Study Officials

  • Dmitriy G Nosov, M.D.

    Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2007

First Posted

July 17, 2007

Study Start

October 1, 2007

Primary Completion

August 1, 2010

Study Completion

August 1, 2010

Last Updated

September 1, 2020

Results First Posted

September 1, 2020

Record last verified: 2020-08

Locations

IN(5)RU(14)UA(7)