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

September 30, 2011 updated by: AVEO Pharmaceuticals, Inc.
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
28

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Jonsson Comprehensive Cancer Center
      • Stanford, California, United States, 94305
        • Stanford University
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • The Methodist Hospital Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ≥ 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

Exclusion Criteria:

  • 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
    • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A
tivozanib (AV-951) plus temsirolimus
Drug: tivozanib (AV-951) plus 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
Other Names:
  • Torisel (temsirolimus)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
To determine the safety and tolerability of tivozanib (AV-951) when given in combination with temsirolimus
Time Frame: 4 weeks (1 cycle)
4 weeks (1 cycle)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
To characterize the pharmacokinetic profile of tivozanib (AV-951) and temsirolimus when administered in combination
Time Frame: 8 weeks (2 cycles)
8 weeks (2 cycles)
To evaluate the antineoplastic activity of tivozanib (AV-951) and temsirolimus when administered in combination
Time Frame: 8 weeks (2 cycles)
8 weeks (2 cycles)
To evaluate the effect of tivozanib (AV-951) and temsirolimus on global and targeted gene expression patterns
Time Frame: 8 weeks (2 cycles)
8 weeks (2 cycles)
To determine the maximum tolerated dose (MTD) of tivozanib (AV-951) when administered in combination with temsirolimus
Time Frame: 4 weeks (1 cycle)
4 weeks (1 cycle)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AVEO Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Joshua Zhang, M.D., AVEO Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 26, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AV-951-07-102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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