Efficacy Study of Sunitinib and Everolimus (Rotational vs Sequential Arm) in Pats. With m Clear Cell Renal Cancer

• Status: Terminated
• Trial end date: 2017-05-08
• Target enrollment: 0
• Participant gender: All

Summary

The objective of this study is to assess the progression-free survival, of patients who receive rotations of sunitinib and everolimus versus patients who receive sunitinib as a first line treatment followed by everolimus when progression occurs.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Associació per a la Recerca Oncologica, Spain
• Collaborators: Novartis; Pivotal S.L.
• Treatments: Everolimus; Sirolimus; Sunitinib

Criteria

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 normal)

• 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 (HCV)

• 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.