ZEBRA: AZD2014 compared to Everolmus in Renal Cancer
- Conditions
- Metastatic Clear Cell Renal CancerMedDRA version: 16.1Level: PTClassification code 10050018Term: Renal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-002874-30-GB
- Lead Sponsor
- Queen Mary University of London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
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
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method