Temsirolimus and Pazopanib in Patients With Advanced Solid Tumors

March 26, 2012 updated by: University of California, Davis

Phase I Study of the Combination of Temsirolimus (CCI-779) and Pazopanib (GW786034) in Patients With Advanced Solid Tumors

The purpose of this study is to test the safety of temsirolimus and pazopanib at different doses. Patients who have an advanced cancer that is not felt to benefit from standard treatment or are no longer responding to other treatment will be asked to take part in this study. The study hypothesis is that temsirolimus and pazopanib can be administered safely in combination and that combined targeting of the mammalian target of rapamycin (mTOR) and vascular endothelial growth factor receptor (VEGFR) signaling pathways will be effective in treating patients with advanced solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite encouraging clinical activity reported with single-agent VEGF inhibitors, mTOR inhibitors, and other novel agents, patients rarely achieve complete disease response and ultimately undergo disease progression. The limited efficacy of single-target inhibition may be due to numerous, overlapping signaling pathways involved in Renal Cell Carcinoma proliferation and growth. A strategy of multi-target "vertical inhibition" of the overlapping aberrant VEGF and mTOR pathways by combination therapy may translate to enhanced efficacy over each single agent alone. We hypothesize that temsirolimus and pazopanib can be administered safely in combination and that combined targeting of the mTOR and VEGFR signaling pathways will be effective in treating patients with advanced solid tumors.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • 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
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective.
  • Age ≥ 18 years old
  • Zubrod (ECOG) Performance Status 0 - 2
  • May have measurable or non-measurable disease.
  • Adequate bone marrow and organ function as assessed by the following within 14 days prior to registration.
  • Any number of prior chemotherapy regimens is allowed.
  • Any prior chemotherapy, immunotherapy or targeted therapy must have been completed at least 2 weeks prior to start of this protocol and all side effects (except alopecia, lymphopenia and hyperglycemia) resolved to grade 1 or less. Any prior radiation must have been completed at least 2 weeks prior to start of therapy.
  • Pregnant or nursing women are ineligible because of the risk to the fetus. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent.
  • Ability to swallow and retain oral medications.

Exclusion Criteria:

  • Prior treatment with an mTOR inhibitor or pazopanib.
  • Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
  • Symptomatic or uncontrolled brain metastasis.
  • Must have a EKG within 14 days of registration and a QTc of < 480 msec. If the initial QTc is > 480 msec, two subsequent EKGs should be obtained within 5 minutes.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C due to the immunosuppressive effects of temsirolimus.
  • Active clinically serious infection > CTCAE Grade 2.
  • Fasting cholesterol > 350mg/dL and fasting triglycerides > 400mg/dL
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy. Therapeutic anticoagulation with warfarin, heparin or low molecular weight heparin is not allowed. Patients may not have had an arterial thrombotic event within the past 6 months.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug.
  • May not take known strong CYP3A4 inducers such as rifampin or St. John's wort or strong CYP3A4 inhibitors such as ketoconazole, diltiazem, or verapamil.
  • Known or suspected allergy to temsirolimus or pazopanib, any similar agents such as the rapamycin analog sirolimus, or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Temsirolimus and Pazopanib
Drug: Temsirolimus, Pazopanib
Patients will be treated on an outpatient basis with both temsirolimus and pazopanib. All patients will receive temsirolimus intravenously (IV) weekly days 1, 8, 15, and 22. Patients will receive oral pazopanib on a daily basis starting day 1. Treatment will be administered on 28 day cycles. Patients will be in this study for a minimum of 8 weeks or 2 cycles.
Other Names:
  • Votrient
  • Torisel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Feasibility and safety of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors.
Time Frame: Every 4 weeks (Cycle)
Every 4 weeks (Cycle)

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine the maximum tolerated dose (MTD) of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors and to recommend a phase II dose for the combination.
Time Frame: Every 4 weeks (Cycle)
Every 4 weeks (Cycle)

Collaborators and Investigators

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

Sponsor

University of California, Davis

Collaborators

GlaxoSmithKline
Pfizer

Investigators

  • Principal Investigator: Primo N Lara, MD, University of California, Davis

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

Helpful Links

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

February 1, 2010

Primary Completion (Actual)

February 1, 2012

Study Completion (Actual)

February 1, 2012

Study Registration Dates

First Submitted

February 16, 2010

First Submitted That Met QC Criteria

February 19, 2010

First Posted (Estimate)

February 22, 2010

Study Record Updates

Last Update Posted (Estimate)

March 28, 2012

Last Update Submitted That Met QC Criteria

March 26, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200917514
  • UCDCC#222 (Other Identifier: University of California Davis)

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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