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A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Bi-monthly Rotations Between Everolimus and Pazopanib in Patients With Advanced or Metastatic Clear Cell Renal Cancer

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

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Trial Information

A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Bi-monthly Rotations Between Everolimus and Pazopanib in Patients With Advanced or Metastatic Clear Cell Renal Cancer

Current practice is to treat with VEGFR-TKI or mTOR inhibitors until progression and then
continue with the next active agent. From a biological perspective, TKI's will most likely
activate compensatory pathways which, may ultimately lead to the development of resistance.
Recent studies suggest that resistance to treatment with TKI may be reversible after
stopping treatment. There is therefore a rationale to alternate treatment to prevent or
delay the occurrence of resistance.

Our hypothesis is that alternating active agents in clear cell renal carcinoma (ccRCC) may
reduce side effects, improve tolerability and compliance of treatment and prolong
progression free survival and overall survival compared to the standard of care.

Inclusion Criteria:

- Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and

- Age ≥ 18 years.

- Histologically confirmed diagnosis of progressive metastatic clear cell renal cell
cancer defined as >10% of the tumor cells having the clear cell phenotype.

- Locally advanced (defined as disease not amenable to curative surgery or radiation
therapy) or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

- Measurable disease.

- No prior systemic anti-cancer treatment against clear cell renal carcinoma.

- Adequate organ system function.

- Non-childbearing potential.

Exclusion Criteria:

- Prior malignancy.

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis.

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding.

- Clinically significant gastrointestinal abnormalities that may affect absorption of
investigational product.

- Presence of uncontrolled infection.

- Known past or present infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV)
or Human Immunodeficiency Virus (HIV).

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula.

- History of one or more of the following cardiovascular conditions within the past 6

1. Cardiac angioplasty or stenting

2. Myocardial infarction

3. Stable or unstable angina pectoris.

4. Coronary artery bypass graft surgery.

5. Symptomatic peripheral vascular disease

6. Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA).

- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg
or diastolic blood pressure (DBP) of ≥ 90mmHg].

- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6

- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any nonhealing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major).

- Evidence of active bleeding or bleeding diathesis.

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.

- Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of
study drug.

- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures.

- Unable or unwilling to discontinue use of prohibited medications or modify the dosing
of interacting drugs for at least 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of study drug and for the duration of the study.

- Pregnant or lactating female.

- Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery
or tumor embolization within 14 days prior to the first dose of Pazopanib OR
Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression free survival

Outcome Time Frame:

Randomization until earliest date of disease progression (according RECIST 1.1 criteria) or death, an expected average of one year

Safety Issue:


Principal Investigator

E.E. Voest, MD/PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UMC Utrecht


Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

November 2011

Completion Date:

February 2015

Related Keywords:

  • Clear Cell Renal Carcinoma
  • Renal carcinoma
  • Resistance
  • Reversible
  • Translational
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms