Improving sunitinib efficacy and tolerability in patients with metastatic clear cell carcinoma of the kidney by using a 14/7 day schedule and toxicity-adjusted dosing

Exclusion Criteria20

• Prior systemic treatment of metastatic renal cell cancer;
• Patients treated with any neoadjuvant or adjuvant systemic therapy;
• Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated;
• Gastrointestinal abnormalities including:
• (a) inability to take oral medication;
• (b) requirement for intravenous alimentation;
• (c) prior surgical procedures affecting absorption including total gastric resection;
• (d) treatment for active peptic ulcer disease in the past 6 months; active gastrointestinal bleeding, unrelated to cancer, as evidenced by haematemesis, haematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
• (e) malabsorption syndromes;
• (f) history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment;
• CYP3A4 inhibitors or inducers: Use with drugs that are known potent CYP3A4 inhibitors or inducers should be avoided if possible. Patients may receive these agents if they are on a stable dose and are planned to continue throughout the study period
• Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of randomization.
• A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
• Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• History of a malignancy (other than renal cell cancer) except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not able to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for 6 months after discontinuing study treatment The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate.
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.