Metastatic Clear Cell Renal Cancer MedDRA version: 16.1 Level: PT Classification code 10050018 Term: Renal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Afinitor
Product Name: Afinitor
Pharmaceutical Form: Tablet
Product Name: AZD2014
Product Code: AZD2014
Pharmaceutical Form: Tablet
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histopathologically confirmed renal cell carcinoma with measurable metastases on CT/MRI imaging. A component of clear cell must be present. 2. Radiological progressive disease on VEGF targeted therapy (RECIST v1.1). Exposure to more than one line of VEGF targeted therapy is acceptable. Previous treatment with initial interferon,n or IL- 2 prior or another experimental agent is acceptable (with the exception of drugs specifically targeting mTOR). 3. Evidence of measurable disease (i.e., =1 malignant tumour mass that can be accurately measured in at least 1 dimension = 20 mm with conventional computerized tomography ([CT]) scan or Magnetic Resonance Imaging ([MRI]), or =10 mm (except lymph nodes which must have short axis = 15 mm) with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. 4. Adequate organ function as defined by the following criteria: a. Total serum bilirubin =1.5 x ULN (patients with Gilbert’s disease exempt), b. Serum transaminases =3.0 x ULN (x5 in the presence of liver metastasis). c. Serum creatinine = 2 x ULN or estimated GFR e.g. Cockcroft and Gault >30ml/min d. Absolute neutrophil count (ANC) = 1.5 x 109/L without growth factor support, e. Platelets = 100 x 109/L 5. Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrolment. This includes the collection of archived tissue. 6. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures 7. ECOG performance status of 0, 1 or 2. 8. Life expectance >12 weeks 9. At least 14 days since the end of prior systemic treatment (e.g. sunitinib, pazopanib, sorafenib or any other approved therapy for renal cancer), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 4.03 grade =1 or back to baseline except for alopecia or hypothyroidism. 21 days gap between bevacizumab and INF (interferon) treatment should exist. 10. Fasting blood sugar =8mmol/l and HbA1C =7% (equivalent to 53 mmol/mol) 11. Males and Females of age =18 years Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1. Previous exposure to mTOR inhibitors for metastatic renal cancer. 2. Females of child-bearing potential. The definition of child-bearing potential: women between menarche and menopause who have not been permanently or surgically sterilised and are capable of procreation. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. 3. Pregnant and Breast feeding women. 4. Any other severe condition (acute/chronic, medical/psychiatric) or laboratory abnormally which the investigator believes would impart excess risk associated with study participation or study drug administration, or would make the patient inappropriate for entry into this study. Specifically the following indications are contraindicated: Hereditary galacto-intolerance, glucose/galactose malabsorbtion and lactose deficiency. 5. Untreated clinically symptomatic brain or meningeal metastases. Patients with evidence of clinically stable brain metastases are eligible providing that they do not require corticosteroids. 6. Any evidence of severe or uncontrolled diseases e.g., unstable or uncompensated respiratory, hepatic or renal disease. 7. Any evidence of interstitial fibrotic lung disease (bilateral, diffuse, parenchymal lung disease). 8. Unresolved toxicity = CTCAE (v 4.03) grade 2 (except alopecia and hypothyroidism) from previous anti-cancer therapy. 9. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ or localised controlled prostate cancer) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion. 10. Uncontrolled diabetes mellitus or hyperlipideamia (> grade 1) 11. Treatment with an investigational drug (not including TKIs) within 21 days prior to the first dose of therapy. If the investigational drug is a TKI then treatment within 14 days prior to the first dose of therapy. 12. Patients who have experienced any of the following procedures or conditions currently or in the preceding 12 months: a. Coronary artery bypass graft b. Angioplasty c. Vascular stent d. Myocardial infarction e. Angina pectoris f. Congestive heart failure new york heart association grade =2 g. Ventricular arrhythmias requiring continuous therapy h. Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled i. Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or j. Any other central nervous system bleeding 13. Mean resting QTcF = 470 msec as per local reading 14. Abnormal ECHO at baseline (left ventricular ejection fraction [LVEF] <50%. 15. Known inherited or acquired immunodeficiency 16. Known active hepatitis B or C infection or HIV. 17. Other concomitant anti-cancer therapy (including LHRH agonists) 18. Previous bone marrow transplant 19. Male or female aged < 18 years 20. Any haemopoietic growth factors (eg, G-CSF, GM-CSF) within 2 weeks prior to receiving study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to investigate if AZD2014 is associated with a delay in progression free survival(PFS)compared to everolimus.;Secondary Objective: a)To evaluate tumour response rate after at least 8 weeks of treatment with the study drugs. B) To compare overall survival of the two group of patients. c) To determine the safety profile of AZD2014 and to compare with that of everolimus.;Primary end point(s): Following patients to progression free survial.;Timepoint(s) of evaluation of this end point: Patients will be followed up for 12 months after randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determining causality of each adverse event (AE) to AZD2014 or Everolimus and grading severity according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Determination of the time from treatment until death. Response assessment (stable disease (SD), partial response (PR) or complete response (CR)) determined according to Response Evaluation Criteria in Solid Tumours (RECIST v 1.1) in all patients receiving at least one cycle of treatment. ;Timepoint(s) of evaluation of this end point: Patients will be followed up for 12 months after randomisation. | — |
Countries
United Kingdom
Contacts
Public ContactZEBRA Trial Coordinator
Centre for Experimental Cancer Medicine, Queen Mary University of London
Outcome results
None listed