A phase 2 trial of EVERolimus alternating with SUNitinib as first line therapy for advanced renal cell carcinoma
- Conditions
- Renal Cell CarcinomaCancer - Kidney
- Registration Number
- ACTRN12609000643279
- Lead Sponsor
- The University of Sydney
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 55
Patients will be eligible for enrollment if they fulfill all of the following criteria:
1. Renal cell carcinoma with a clear cell component confirmed by histology or cytology
2. Advanced disease: metastatic OR locally advanced OR locally recurrent; AND, not suitable for resection
3. Male or female, aged 18 years or older
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. Low or intermediate Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk score (8, 9), i.e. no more than 2 of the following: Karnofsky performance status 1.5 times institutional upper limit of normal; Anaemia (haemoglobin less than institutional lower limit of normal); Hypercalcemia (corrected serum calcium >2.5 mmol/L); Interval since diagnosis less than 1 year.
6. Target and/or non-target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (15). Patients participating in Positron Emission Tomography (PET) studies must have a lesion assessable by PET (at least 2cm in diameter in an organ not subject to undue PET artefact, as determined by the site Principal Investigator in conjunction with nuclear medicine physicians).
7. Expected survival of at least 3 months.
8. Within 3 weeks prior to registration, vital laboratory parameters should be within the normal range, except for the following parameters, which should be within the ranges specified: Neutrophils >/= 1.5 x 109/L; Platelets >/= 90 x 109/L; International Normalised Ratio (INR) 9. 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).
10. Systolic blood pressure 11. Able to commence treatment within 7 days of registration.
12. Willing and able to comply with follow-up and all other protocol requirements.
13. Written informed consent
Patients will be excluded from the study for any of the following reasons:
1. Prior treatment with Vascular Endothelial Growth Factor (VEGF)-targeting agents (e.g. bevacizumab) or multi-kinase inhibitors (e.g. sorafenib or sunitinib), or mammalian Target of Rapamycin (mTOR)-targeting agents (e.g. everolimus or temsirolimus).
2. Active central nervous system metastases. Patients may be eligible if they have central nervous system metastases that have been adequately treated (surgery or radiotherapy), do not require ongoing corticosteroids for control of symptoms, and have had no evidence of progression for at least three months.
3. Other malignancy diagnosed within the last 5 years, except the following if adequately treated: superficial Squamous Cell Carcinoma (SCC) or Basal Cell Carcinoma (BCC) of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer.
4. Treatment with an investigational agent in the last 4 weeks.
5. Known to be Human Immunodeficiency Virus (HIV) positive (testing not mandatory unless clinically indicated).
6. Evidence of chronic hepatitis due to Hepatitis B Virus (HBV) (HBV surface antigen positive) or Hepatitis C Virus (HCV) (HCV ribonucleic acid (RNA) positive). All potential participants will be tested for HBV surface antigen, HBV core antibody, HCV antibody, and HCV RNA if the HCV Ab is positive.
7. Clinically significant heart disease (New York Heart Association (NYHA) Class III or IV).
8. History of hypertension requiring hospitalisation.
9. Other serious illnesses, e.g. active infection requiring antibiotics, bleeding disorders.
10. Immunotherapy or chemotherapy in the last 4 weeks (6 weeks for nitrosoureas).
11. Major surgery in the last 4 weeks, or planned in the next 6 weeks.
12. Radiation therapy in the last 2 weeks, or planned in the next 6 weeks. Any acute adverse effects of recent radiation must have resolved prior to registration. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one lesion that has not been irradiated or which has progressed following radiotherapy.
13. National Cancer Institute of the USA Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 grade 3 or worse haemorrhage in last 4 weeks.
14. 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.
15. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication.
16. 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.
17. Uncontrolled diabetes as defined by fasting serum glucose >1.5 X Upper Limit of Normal (ULN).
18. Pregnancy (negative pregnancy test required for women of child-bearing potential), lactation
19. Inadequate contraception. Women must be post-menopausal, surgically sterile, or use 2 reliable forms of contraception. Men must be surgically sterile or use a barrier method of contraception.
20. Known allergy or hypersensitivity to everolimus, sunitinib or iodine.
21. Medical or psychiatric condition that compromises the patient's ability to give informed consent.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method