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Renal Cell CarcinomaPhase 1NCT00563147

A Phase 1b, Open-Label, Dose-Finding Study to Evaluate the Safety of Tivozanib (AV-951) in Combination With Temsirolimus in Subjects With Metastatic Renal Cell Carcinoma

A Phase 1 study testing tivozanib (AV-951) plus temsirolimus in people with Renal Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 5 sites in United States.

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

The purpose of this study is to test the safety and tolerability of tivozanib (AV-951) and Torisel™ given in combination for renal cell cancer. The study will also assess the effects of the combination of tivozanib (AV-951) and Torisel™ on the tumor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
tivozanib (AV-951) plus temsirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
5 sitesUnited States
Study dates
Nov 2007to Feb 2011
Phase
Phase 1
Are there results?
None posted in the registry

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
  • Histologically confirmed renal cell carcinoma with a clear cell component
  • Documented progressive disease
  • Measurable disease by RECIST criteria
  • No more than 1 prior VEGF receptor targeted therapy; no prior treatment with temsirolimus or other drugs targeting the mTOR pathway
  • Karnofsky performance status > 70%; life expectancy ≥ 3 months
  • Ability to give written informed consent

Who cannot join

  • Known hypersensitivity to temsirolimus or its metabolites (including sirolimus), polysorbate 80, or to any other component of the temsirolimus formulation
  • Primary CNS malignancies; active CNS metastases
  • Hematologic malignancies (including leukemia in any form, lymphoma, and multiple myeloma)
  • Any of the following hematologic abnormalities:
  • Hemoglobin < 9.0 g/dL
  • ANC < 1500 per mm3
Show all 47Show fewer
  • Platelet count < 100,000 per mm3
  • Any of the following serum chemistry abnormalities:
  • Fasting serum cholesterol > 350 mg/dL
  • Fasting triglycerides > 400 mg/dL
  • Total bilirubin > 1.5 × ULN
  • AST or ALT > 2.5 × ULN (or > 5 x ULN in subjects with liver metastasis)
  • Serum albumin < 3.0 g/dL
  • Creatine > 1.5 × ULN (or calculated CLCR <50 mL/min/1.73 m2)
  • Proteinuria > 2.5 g/24 hours or 3+ with urine dipstick
  • Significant cardiovascular disease, including:
  • Active clinically symptomatic left ventricular failure
  • Active hypertension (diastolic blood pressure > 100 mmHg). Subjects 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 2 or more antihypertensive medications
  • Myocardial infarction within 3 months prior to administration of first dose of study drug
  • Subjects with delayed healing of wounds, ulcers, and/or bone fractures
  • Pulmonary hypertension or pneumonitis
  • Serious/active infection; infection requiring parenteral antibiotics
  • Inadequate recovery from any prior surgical procedure; major surgical procedure within 6 weeks prior to study entry
  • Uncontrolled psychiatric disorder, altered mental status precluding informed consent or necessary testing
  • Inability to comply with protocol requirements
  • Ongoing hemoptysis or history of clinically significant bleeding
  • Cerebrovascular accident within 12 months of study entry, or peripheral vascular disease with claudication on walking less than 1 block
  • Deep venous thrombosis or pulmonary embolus within 6 months of study entry and/or ongoing need for full-dose oral or parenteral anticoagulation
  • Subjects with a "currently active" second primary malignancy other than non-melanoma skin cancers. Subjects are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy and are considered by their physician to be < 30% risk of relapse.
  • Pregnant or lactating women
  • Known concomitant genetic or acquired immune suppression disease such as HIV
  • Prohibited medications:
  • VEGF receptor (VEGFR) targeted therapy within 4 weeks prior to and during study
  • Other signal transduction inhibitors, monoclonal antibodies, etc., within 4 weeks prior to and during study
  • Immunotherapy or biological response modifiers within 4 weeks prior to and during study
  • Systemic hormonal therapy within 4 weeks prior to and during study, with the exception of:
  • Hormonal therapy for appetite stimulation or contraception
  • Nasal, ophthalmic, and topical glucocorticoid preparations
  • Oral replacement therapy for adrenal insufficiency
  • Low-dose maintenance steroid therapy for other conditions
  • Herbal preparations/supplements (except for a daily multivitamin/mineral supplement not containing herbal components) within 2 weeks prior to or during study
  • Any experimental therapy 4 weeks prior to and during study
  • Radiotherapy:
  • At least 2 weeks since prior local radiation therapy (ie, involving <25% of bone marrow) at the time of study entry
  • At least 4 weeks since prior radiation therapy involving ≥ 25% of bone marrow
  • Treatment with CYP3A4 inducers or inhibitors during the study

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • The Methodist Hospital Research Institute

    Houston, Texas, 77030

  • UCLA Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Stanford University

    Stanford, California, 94305

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

The purpose of this study is to test the safety and tolerability of tivozanib (AV-951) and Torisel™ given in combination for renal cell cancer. The study will also assess the effects of the combination of tivozanib (AV-951) and Torisel™ on the tumor. 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. Temsirolimus is an mTOR inhibitor which is approved for the treatment of advanced renal cell carcinoma.

Read the detailed description

This is a Phase 1b, open-label, dose-finding study of tivozanib (AV-951) in combination with temsirolimus to include approximately 36 subjects with metastatic renal cell carcinoma (mRCC). This study is designed to evaluate the safety, tolerability, dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetic, pharmacogenomic, and antineoplastic activity of tivozanib (AV-951) when administered in combination with temsirolimus. Tivozanib (AV-951) will be administered once daily for 3 weeks beginning on Day 1 of Cycle 1, followed by 1 week off (1 cycle = 4 weeks). Temsirolimus will be administered intravenously once weekly starting on Day 8 of Cycle 1.

Being tested
tivozanib (AV-951) plus temsirolimus
Keywords
tivozanib, AV-951
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) plus temsirolimusDrug

    Also called Torisel (temsirolimus)

    ascending doses of tivozanib (AV-951) capsules administered orally for 21 days with discontinuation for 7 days; ascending doses of temsirolimus administered intravenously every 7 days

Study groups in NCT00563147
Study groupRoleWhat they receive
AExperimentaltivozanib (AV-951) plus temsirolimus
Receives: Drug: tivozanib (AV-951) plus temsirolimus

What is being measured

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

  1. To determine the safety and tolerability of tivozanib (AV-951) when given in combination with temsirolimus

    Measured: 4 weeks (1 cycle)

Secondary outcomes (4)

  1. To characterize the pharmacokinetic profile of tivozanib (AV-951) and temsirolimus when administered in combination

    Measured: 8 weeks (2 cycles)

  2. To evaluate the antineoplastic activity of tivozanib (AV-951) and temsirolimus when administered in combination

    Measured: 8 weeks (2 cycles)

  3. To evaluate the effect of tivozanib (AV-951) and temsirolimus on global and targeted gene expression patterns

    Measured: 8 weeks (2 cycles)

  4. To determine the maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with temsirolimus

    Measured: 4 weeks (1 cycle)

Timeline

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

  1. First posted26 Nov 2007 (estimated)
  2. Study startNov 2007
  3. Primary completionNov 2010
  4. Study completionFeb 2011

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00563147
Sponsor's protocol ID
AV-951-07-102
Status last verified
Sep 2011
First submitted
21 Nov 2007
Last updated
4 Oct 2011
Results posted
No
Data monitoring committee
No

Publications

  • Fishman MN, Srinivas S, Hauke RJ, Amato RJ, Esteves B, Cotreau MM, Strahs AL, Slichenmyer WJ, Bhargava P, Kabbinavar FF. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. Eur J Cancer. 2013 Sep;49(13):2841-50. doi: 10.1016/j.ejca.2013.04.019. Epub 2013 May 28.

    PubMed 23726267

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing tivozanib (AV-951) plus temsirolimus in people with Renal Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 5 sites in United States.

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 7 inclusion and 47 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 4 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To determine the safety and tolerability of tivozanib (AV-951) when given in combination with temsirolimus (time frame: 4 weeks (1 cycle)). 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 NCT00563147, 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 4 Oct 2011.

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