S0718 Pazopanib and Temsirolimus in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00788580
Recruitment Status : Withdrawn (Study was discontinued.)
First Posted : November 11, 2008
Last Update Posted : March 6, 2015
National Cancer Institute (NCI)
Information provided by:
Southwest Oncology Group

Brief Summary:

RATIONALE: Pazopanib and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib may also blocking blood flow to the tumor. Giving pazopanib together with temsirolimus may be an effective treatment for advanced solid tumors.

PURPOSE: This phase I trial is studying the side effects and best dose of temsirolimus when given together with pazopanib in treating patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: pazopanib hydrochloride Drug: temsirolimus Procedure: immunoenzyme technique Procedure: laboratory biomarker analysis Procedure: pharmacological study Phase 1

Detailed Description:


  • To investigate the safety and feasibility of temsirolimus and pazopanib when given in combination in patients with advanced solid tumors.
  • To recommend the maximum tolerated dose of this regimen in these patients.
  • To investigate the pharmacokinetics of temsirolimus alone and in combination with pazopanib in these patients.
  • To investigate the effects of this regimen on relevant biological markers.
  • To preliminarily report objective response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive temsirolimus IV over 30 minutes on days 1, 8,15, and 22 and oral pazopanib hydrochloride once daily on days 4-28 in course 1 and days 1-28 in all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are obtained periodically for evaluation of the pharmacokinetics of temsirolimus and pazopanib, plasma and serum angiogenic and cachectic factors (e.g., VEGF, bFGF, PlGF and SDF-1) by enzyme-linked immunosorbent assay, and biological markers in the mTOR/PI3/Akt, Ras/MAPK, VEGFR, PDGFR, and HIF-1 pathways.

After completion of study therapy, patients are followed for 28 days.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Primary Purpose: Treatment
Official Title: S0718: Phase I Study Evaluating The Combination of GW786034 (Pazopanib; NSC-737754; IND-XXXX) and CCI-779 (Temsirolimus; NSC-683864; IND-XXXX) in Patients With Advanced Solid Tumors

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. Safety as assessed by NCI CTCAE v3.0
  2. Feasibility of the drug combination
  3. Maximum tolerated dose of temsirolimus in combination with pazopanib

Secondary Outcome Measures :
  1. Pharmacokinetics of temsirolimus alone and in combination with pazopanib
  2. Relevant biological markers
  3. Objective response as assessed by RECIST criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Cytologically or pathologically verified cancer that is of advanced stage and for which there is no effective therapy

    • No lymphoma
  • Measurable or nonmeasurable disease
  • Previously irradiated (whole brain or gamma knife) brain metastases allowed provided there is no requirement for corticosteroids or anticonvulsants


  • Zubrod performance status 0-2
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 9 g/dL (without transfusions)
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if liver metastases present)
  • Bilirubin normal
  • Serum creatinine ≤ 1.5 times ULN OR measured creatinine clearance OR calculated creatinine clearance ≥ 60 mL/min
  • QTC interval < 480 msec on baseline ECG OR average QTC < 480 msec on baseline plus 2 additional screening ECG's
  • Fasting cholesterol < 350 mg/dL
  • Fasting triglycerides < 400 mg/dL
  • No uncontrolled hypertension, arterial thrombotic event, or bleeding on therapeutic anticoagulation with warfarin or heparin (including low molecular weight heparin) within the past 6 months
  • Able to swallow enteral medications
  • No feeding tubes
  • No intractable nausea or vomiting
  • No gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn, ulcerative colitis)
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to rapamycin analogs (e.g., sirolimus and everolimus)
  • No known HIV positivity
  • No uncontrolled intercurrent illness including, but not limited to, the following:

    • Ongoing or serious active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • History of myocardial infarction
    • Cerebrovascular accident within 3 months of study entry
    • Uncontrolled diarrhea
    • Psychiatric illness or social situation that would limit compliance with study requirements
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception, including barrier methods
  • Willing to undergo pharmacokinetic (PK) sampling and blood submission for PK and translational medicine studies


  • Recovered from all prior therapy
  • No prior pazopanib hydrochloride or temsirolimus
  • More than 28 days since prior major surgery, chemotherapy, biologic therapy, or immunotherapy
  • More than 28 days since prior investigational agents
  • At least 14 days since prior radiotherapy
  • No concurrent rapamycin (sirolimus)
  • No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), CYP3A4 inducers (e.g., rifampin or St. John's wort), or CYP3A4 inhibiting agents or substrates (e.g., ketoconazole, diltiazem, or verapamil)
  • No concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of this cancer while on this protocol

    • No live vaccines
    • Luteinizing-hormone releasing-hormone agonists allowed
  • Concurrent prophylactic warfarin (≤ 1 mg/day) allowed
  • Concurrent bisphosphonate or erythropoietin or its analogue allowed, if deemed appropriate by the treating physician

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00788580

Sponsors and Collaborators
Southwest Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Claire F. Verschraegen, MD University of New Mexico Cancer Center Identifier: NCT00788580     History of Changes
Other Study ID Numbers: S0718
First Posted: November 11, 2008    Key Record Dates
Last Update Posted: March 6, 2015
Last Verified: March 2015

Keywords provided by Southwest Oncology Group:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents