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Carcinoma, Renal CellPhase 2NCT00502307

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

A Phase 2 study testing Tivozanib (AV-951) in people with Carcinoma, Renal Cell, run by AVEO Pharmaceuticals, Inc. at 26 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Renal Cell
What is being tested?
Tivozanib (AV-951)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
272 participants
Where
26 sitesin 3 countries
Study dates
Oct 2007to Aug 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

26 sites in 3 countries.

26 sites in 3 countries

Russia14 sites

  • Study site

    Astrakhan

  • Study site

    Kazan'

  • Study site

    Moscow, 125284

  • Study site

    Moscow, 129128

  • Study site

    Moscow

  • Study site

    Obninsk

  • Study site

    Pyatigorsk

  • Study site

    Rostove-on-Don

  • Study site

    Saint Petersburg

  • Study site

    Sochi

  • Study site

    Tomsk

  • Study site

    Ufa

  • Study site

    Velikiy Novgorod

  • Study site

    Yoshkar-Ola

Other trials in Russia

Ukraine7 sites

  • Study site

    Cherkassy

  • Study site

    Dnipro

  • Study site

    Donetsk

  • Study site

    Kharkiv

  • Study site

    Lviv

  • Study site

    Uzhhorod

  • Study site

    Zaporizzhya

Other trials in Ukraine

India5 sites

  • Study site

    Kolkata

  • Study site

    Mumbai

  • Study site

    New Delhi

  • Study site

    Pune

  • Study site

    Vellore, Tamil Nadu, 632004

Other trials in India

About this study

Official title: A Phase 2, Placebo-Controlled, Randomized, Discontinuation Trial of Tivozanib (AV-951) in Patients With Renal Cell Carcinoma

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.

Read the 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
Being tested
Tivozanib (AV-951), Placebo comparator
Keywords
Renal Cell Carcinoma, AV-951, tivozanib
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tivozanib (AV-951)Drug

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

  • Placebo comparatorDrug

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

Study groups in NCT00502307
Study groupRoleWhat they receive
1ExperimentalTivozanib (AV-951) administered as a solid dosage form daily for three weeks per month
Receives: Drug: Tivozanib (AV-951)
2Placebo comparatorsolid oral capsule containing excipients dosed daily for three weeks per month
Receives: Drug: Placebo comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 28 weeks after study entry

  2. 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.

    Measured: 16 weeks after study entry

  3. 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.

    Measured: 28 weeks after study entry

Secondary outcomes (5)

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

    PFS after randomization in the ITT population was described using the Kaplan-Meier methodology. PFS was compared across treatment arms using the log-rank test.

    Measured: 28 weeks from study entry

  2. Overall Progression-free Survival (From Start of Treatment)

    Number of subjects with Overall PFS (from start of treatment) was estimated using the Kaplan-Meier methodology. Subjects randomized to receive placebo were censored at randomization. Withdrawals are also censored. An alternative analysis was conducted in which PFS for subjects randomized to receive tivozanib was weighted more heavily to compensate for the information loss from randomization of other subjects to receive placebo. Additional analyses in which withdrawal was considered a PFS event were also conducted.

    Measured: 12 months from study entry

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

    Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.

    Measured: 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

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

    Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.

    Measured: 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

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

    Tivozanib concentrations in human serum were determined. The PK population included all subjects who had taken at least 1 dose of tivozanib and whose PK profile(s) were evaluable. All subjects received 1.5 mg tivozanib (1.3397 mg free base) in Cycle 1.

    Measured: 28 weeks from study entry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionAug 2010
  4. Study completionAug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
272 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00502307
Sponsor's protocol ID
AV-951-07-201
Status last verified
Aug 2020
First submitted
16 Jul 2007
Last updated
1 Sep 2020
Data monitoring committee
No

Publications

  • 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.

    PubMed 37315114

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tivozanib (AV-951) in people with Carcinoma, Renal Cell, run by AVEO Pharmaceuticals, Inc. at 26 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Russia, Ukraine, India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Adverse Events (AEs)/Serious AEs (SAEs) (time frame: 28 weeks after study entry). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00502307, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2020.

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