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Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment

Phase 2
18 Years
Open (Enrolling)
Carcinoma, Renal Cell

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Trial Information

Continuous Access to Advanced and Metastatic Renal Cell Carcinoma Therapy With Everolimus Post Pazopanib Treatment

A non-randomised, open label, single-arm phase II study to evaluate the efficacy and safety
of 1st-line pazopanib followed by 2nd-line everolimus in patients with previously untreated
advanced or metastatic renal cell carcinoma. Subjects will receive initial therapy with
pazopanib, followed, on progression, by 2nd-line therapy with everolimus. Study treatment,
sequential treatment with pazopanib followed by everolimus, will continue until disease
progression, unacceptable toxicity, withdrawal of consent or death.

Inclusion Criteria:

1. Written informed consent

2. Diagnosis of renal cell carcinoma with clear-cell component histology.

3. Locally advanced/metastatic renal cell carcinoma

4. Measurable lesion (RECIST 1.1) on physical exam or as CT/MRI

5. No prior systemic therapy for advanced/metastatic RCC

6. Karnofsky performance scale >=70

7. Age >=18 years

8. A female is eligible to enter and participate in this study if she is of:
non-childbearing/agrees to use adequate contraception

9. A male with female partner of childbearing potential must have vasectomy/agree to use
effective contraception from two weeks prior to administration of the 1st dose of
study treatment for a period of time after the last dose of study treatment

10. Adequate organ function

11. Able to swallow and retain orally administered medication and must not have
clinically significant GIT abnormalities that may alter absorption

Additional criterion for inclusion in the everolimus treatment:

12. The date of disease progression must be within six months of stopping pazopanib or
during treatment with pazopanib

Exclusion Criteria:

1. Pregnant/lactating

2. History of another malignancy (unless have been disease-free for 3 years)

3. History or clinical evidence of Central nervous system metastases (unless have
previously-treated CNS metastases and who meet both of the following criteria: a) are
asymptomatic and b) have no requirement for steroids or enzyme-inducing
anticonvulsants in prior 6 month time interval.

4. Clinically significant gastrointestinal abnormalities including, but not limited to:
malabsorption syndrome, major resection of the stomach or small bowel that could
affect the absorption of study drug, active peptic ulcer disease, known intraluminal
metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative
colitis, or other gastrointestinal conditions with increased risk of perforation,
history of abdominal fistula, gastrointestinal perforation, or intra abdominal

5. Moderate to severe hepatic impairment (Child-Pugh Class C)

6. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
that could interfere with patient's safety, obtaining informed consent or compliance
to the study.

7. Subjects receiving chronic treatment with corticosteroids/other immunosuppressive

8. Subjects with a known history of HIV seropositivity

9. Subjects with active bleeding, bleeding diathesis or on oral anti-vitamin K
medication (except low dose coumadin)

10. Presence of any severe or uncontrolled medical conditions/infection.

11. Currently receiving chemotherapy, immunotherapy or radiotherapy

12. Corrected QT interval (QTc) > 480 milliseconds

13. History of any one or more of the following cardiovascular conditions within the past
12 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, as defined by the New York Heart Association

14. Poorly controlled hypertension (defined as systolic blood pressure of >=140mmHg or
diastolic blood pressure of >=90mmHg).

15. History of cerebrovascular accident including transient ischemic attack, pulmonary
embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless
recent DVT have been treated with therapeutic anti-coagulating agents for at least 6

16. Major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any non-healing wound, fracture, or ulcer.

17. Evidence of active bleeding or bleeding susceptibility.

18. Known endobronchial lesion and/or lesions infiltrating major pulmonary vessels that
increase the risk of pulmonary hemorrage

19. Recent haemoptysis in excess of 2.5ml within eight weeks of first dose of study drug.

20. Use of an investigational agent, including an investigational anti-cancer agent,
within 30 days or 5 half-lives, whichever is longer, prior to the first dose of study

21. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia.

22. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib or everolimus, to other rapamycin derivatives or to
any other excipients.

Additional criterion for exclusion in the everolimus treatment:

23 The subject is felt by the investigator to be unsuitable (on the basis of health,
compliance, or for any other reason) for inclusion in the study.

Type of Study:


Study Design:

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

Outcome Measure:

Median progression free survival on everolimus

Outcome Description:

Median progression free survival on everolimus as second line treatment post pazopanib as first line

Outcome Time Frame:

Everolimus treatment until earliest date of disease progression or death, assessed up to 30 months after the last patient has been enrolled

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Australia: Human Research Ethics Committee

Study ID:




Start Date:

April 2012

Completion Date:

February 2015

Related Keywords:

  • Carcinoma, Renal Cell
  • Renal cell carcinoma
  • GW786034
  • Everolimus
  • Pazopanib
  • Carcinoma
  • Carcinoma, Renal Cell