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A Phase I Study of Pazopanib and Everolimus in Patients With Advanced Solid Tumors and Previously Treated Kidney Cancer

Phase 1
18 Years
Open (Enrolling)
Solid Tumor, Kidney Cancer

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Trial Information

A Phase I Study of Pazopanib and Everolimus in Patients With Advanced Solid Tumors and Previously Treated Kidney Cancer

- This protocol has two parts, Phase I and Expansion Cohort. Once the maximum tolerated
dose has been identified in the Phase I portion, an expansion cohort of patients with
metastatic or locally advanced unresectable kidney cancer will be enrolled.

- Each treatment cycle lasts 4 weeks during which the participant will be taking
pazopanib and everolimus orally daily.

Inclusion Criteria:

- Phase I: Participants must have histologically confirmed malignancy that is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effected.

- Expansion Cohort Only: Participants must have histologically or cytologically
confirmed metastatic or locally advanced unresectable kidney cancer.

- Expansion Cohort Only: Participants must have measurable disease, defined as at least
one lesion that can be accurately measured in at least one dimension at 20mm or
greater with conventional techniques or as 10mm or greater with spiral CT.

- Expansion Cohort Only: Previously treated with at least one anti-angiogenic agent,
including but not limited to bevacizumab, sunitinib, or sorafenib. No more than 4
lines of prior systemic therapy for kidney cancer, mTOR pathway inhibitors other than
RAD001 are allowed.

- 18 years of age or older

- Life expectancy of greater than 3 months

- ECOG performance status of 0 or 1

- Normal organ and marrow function as outlined in the protocol

- Able to swallow oral medications

- Resolution of any pre-existing toxicity from prior therapy to NCI CTCAE v4.0 grade 1
or less

- Women are eligible to participate if she is of non-child bearing potential or agrees
to use adequate contraception

- Female subjects who are lactating should discontinue nursing prior to the first dose
of study drug and should refrain from nursing throughout the treatment period and for
14 days following the last dose of study drug

- A male with a female partner of childbearing potential must use a barrier method of
contraception or abstinence during the study

Exclusion Criteria:

- Participants who have had chemotherapy or radiotherapy within 4 weeks prior to
entering the study or thos who have not recovered from adverse events due to agents
administered more than 4 weeks earlier. Current treatment with leuprolide or other
GnRH agonists is permitted on the Phase 1 portion of the study.

- Participants may not be receiving any other study agents.

- Prior RAD001 or pazopanib therapy

- History of clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 weeks prior to the first dose of study drug.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib or everolimus

- History of any of the following cardiovascular conditions within the past 6 months:
Cardiac angioplasty or stenting; myocardial infarction; unstable angina; coronary
artery by-pass graft surgery; symptomatic peripheral vascular disease; Class III or
IV congestive heart failure

- Poorly controlled hypertension

- History of cerebrovascular accident, pulmonary embolism, or untreated deep venous
thrombosis within the past 6 months

- Prior major surgery or trauma within 28 days prior to first dose of study drug,
and/or not recovered from effects of that surgery, and/or presences of an non-healing
wound, fracture or ulcer, or patients that may require surgery during the course of

- Evidence of active bleeding or bleeding diathesis

- Known endobronchial lesions or involvement of large pulmonary vessels by tumor

- Hemoptysis within 6 weeks of the first dose of study drug

- Clinically significant gastrointestinal abnormalities that may increase the risk of
GI bleeding

- Expansion Cohort Only: Currently active second malignancy other than non-melanoma
skin cancers

- Presence of uncontrolled infection

- Liver disease such as chronic cirrhosis, active hepatitis or chronic persistent

- Uncontrolled diabetes

- Pregnant or breastfeeding

- Chronic treatment with systemic corticosteroids or other immunosuppressive agent

- Treatment with strong CYP3A4 inhibitors

- Treatment with strong CYP3A4 inducers

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period

- Prolongation of corrected QT interval > 480msecs

- History of malabsorption syndrome, disease significantly affecting gastrointestinal
function or major resection of stomach or small bowel that could interfere with
absorption, distribution, metabolism, or excretion of study drugs

- Any ongoing toxicity from prior anti-cancer therapy that is greater than grade 1
and/or that is progressing in severity.

- Any serious and/or pre-existing medical, psychiatric, or other condition that could
interfere with subject safety, obtaining informed consent or compliance with study

- HIV-positive individuals on combination antiretroviral therapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

To determine the maximum tolerated dose and dose limiting toxicities of the combination of pazopanib and everolimus

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Jonathan Rosenberg, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2010

Completion Date:

December 2013

Related Keywords:

  • Solid Tumor
  • Kidney Cancer
  • RAD001
  • pazopanib
  • everolimus
  • advanced cancer
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Neoplasms



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115