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A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Rotations Between SUNitinib and Everolimus Versus Sequential Treatment of 1st lIne Sunitinib and 2nd Line EverolimuS Until Progression in Patients Metastatic Clear Cell Renal Cancer

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

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Trial Information

A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Rotations Between SUNitinib and Everolimus Versus Sequential Treatment of 1st lIne Sunitinib and 2nd Line EverolimuS Until Progression in Patients Metastatic Clear Cell Renal Cancer

This is an open-label, randomized phase II study to investigate the feasibility of
alternating cycles of treatment with sunitinib and everolimus compared to sequential
treatment of sunitinib followed by everolimus.

The study population consists of adult patients (over 18 years old) with clear cell mRCC
(Metastatic Renal Cell Cancer) who have not received prior therapy for their metastatic

The purpose of the study is to determine the progression free survival, feasibility and
safety profile of the experimental arm compared to standard of care.

In the experimental arm alternating treatment will consist of repeating cycles of 24 weeks
of treatment consisting of 12 weeks of sunitinib 4weeks on 2 weeks off, 50 mg pd followed by
12 weeks of everolimus 10 mg per day 11 weeks on 1 week off in patients with metastatic
clear cell renal cancer. The comparative arm will be the standard regimen of sunitinib (50
mg pd 4/2) until progression, followed thereafter by everolimus (10 mg per day continuously,
11/1) until progression.

Inclusion Criteria:

- Renal cell carcinoma with a predominant clear cell component confirmed by histology.

- Advanced disease: metastatic AND, not suitable for resection

- Male or female, aged 18 years or older

- ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 or 1

- Low or intermediate MSKCC (Memorial Sloan Kettering Cancer Center) prognostic risk
score,i.e. no more than 2 of the following:

- Karnofsky performance status (<80%)

- Low serum hemoglobin (≤ 13 g/dL for males and ≤ 11.5 g/dL for females)

- High corrected serum calcium (≥ 10 mg/dL)

- Target and/or non-target lesions according to RECIST 1.1 ( Response Evaluation
Criteria in Solid Tumors)

- Expected survival of at least 3 months.

- No prior systemic treatment. But adjuvant treatment is ok if stopped from ≥ 24 months

- Adequate bone marrow function as shown by:

- Adequate liver function as shown by:

- Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN (upper limit of

- Left ventricular ejection fraction ≥55% on gated cardiac blood pool scan, or normal
left ventricular function and fractional shortening on echocardiogram (according to
institutional limits).

- SBP (systolic blood pressure) ≤140mmHg and DBP (diastolic blood pressure)

- 90mmHg (it is acceptable to initiate antihypertensive treatment prior to
registration to achieve these goals).

- Able to commence treatment within 7 days of registration.

- Willing and able to comply with follow-up and all other protocol requirements.

- Written informed consent

Exclusion Criteria:

- Prior treatment with VEGF-targeting agents or multi-kinase inhibitors or
mTOR-targeting agents

- Active central nervous system metastases.

- Other malignancy diagnosed within the last 5 years, except the following if
adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of
skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer.

- Treatment with an investigational agent in the last 4 w.

- Known to be HIV positive.

- Evidence of chronic hepatitis due to hepatitis B virus (HBV) or hepatitis C virus

- Clinically significant heart disease (NYHA Class III or IV)

- History of hypertension requiring hospitalization.

- Other serious illnesses,

- Immunotherapy or chemotherapy in the last 4 w (6 weeks for nitrosoureas)

- Major surgery in the last 4 w, or planned in the next 6 w

- Radiation therapy in the last 2 w, or planned in the next 6 w

- NCI CTCAE (Common Toxicity Criteria for Adverse Effects) version 4.0 grade 3 or worse
hemorrhage in last 4 w.

- Any of the following in the last year: myocardial infarction, severe/unstable angina,
coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, or pulmonary embolism.

- Pre-existing thyroid abnormality with thyroid function that cannot be maintained in
the normal range with medication.

- Ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 grade ≥2, atrial fibrillation
of any grade, or prolongation of the corrected QT interval (QTc) to >450 msec for
males or >470 msec for females

- Uncontrolled diabetes as defined by fasting serum glucose >1.5 X ULN.

- Pregnancy,lactation. Inadequate contraception.

- Known allergy or hypersensitivity to everolimus, sunitinib or iodine.

- Medical or psychiatric condition that compromises the patient's ability to give
informed consent.

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 (PFS) rate 1 year

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Joaquim Bellmunt, MD/PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Associacio Per la Recerca Oncológica (APRO)


Spain: Spanish Agency of Medicines

Study ID:




Start Date:

October 2012

Completion Date:

February 2015

Related Keywords:

  • Metastatic Renal Cell Carcinoma
  • cancer
  • renal
  • metastatic
  • clear
  • cell
  • Sunitinib
  • Everolimus
  • Alternating
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms