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

Phase 1
18 Years
Not Enrolling
Solid Tumors

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Trial Information

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

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.

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility and safety of temsirolimus and pazopanib when given in combination to patients with advanced solid tumors.

Outcome Time Frame:

Every 4 weeks (Cycle)

Safety Issue:


Principal Investigator

Primo N Lara, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, Davis


United States: Food and Drug Administration

Study ID:




Start Date:

February 2010

Completion Date:

February 2012

Related Keywords:

  • Solid Tumors
  • Temsirolimus, Pazopanib
  • Neoplasms



University of California Davis Cancer Center Sacramento, California  95817