Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000643279
Ethics application status
Approved
Date submitted
13/07/2009
Date registered
30/07/2009
Date last updated
3/06/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A phase 2 trial of EVERolimus alternating with SUNitinib as first line therapy for advanced renal cell carcinoma
Scientific title
A phase 2 trial evaluating the effect of Everolimus alternating with Sunitinib on progression-free survival in patients with advanced renal cell carcinoma.
Secondary ID [1] 251767 0
ANZUP 0901
Universal Trial Number (UTN)
Trial acronym
EVERSUN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Renal Cell Carcinoma 237237 0
Condition category
Condition code
Cancer 239557 239557 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two six-weekly cycles comprising four weeks of oral sunitinib 50 mg once daily followed by two weeks rest, followed by five weeks of oral everolimus 10 mg once daily followed by one week rest are administered (12 week treatment intervention in total). Cycles will continue consecutively until disease progression or toxicity.
Intervention code [1] 236928 0
Treatment: Drugs
Comparator / control treatment
N/A - Single arm trial.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 238354 0
To determine proportion of patients alive and progression-free at 6 months (progression or death) as determined by patient visits and assessment of progression based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
Timepoint [1] 238354 0
6 months following commencement of treatment.
Secondary outcome [1] 244789 0
Proportion of patients eligible to start their second cycle of therapy within 14 weeks of their first dose of therapy. Patients completing treatment with non-protocol specified modifications will not be counted as successes. The regimen would be considered feasible if 80% or more of patients were able to complete cycle 1 and proceed to cycle 2 without more than two weeks delay. The regimen would not be feasible if 60% or fewer patients were able to complete cycle 1 and proceed to cycle 2 without more than two weeks delay. Additional factors to be considered in terms of feasibility will include number of treatment cycles received, dose intensity, proportion of patients requiring dose modification, proportion of patients stopping treatment due to toxicity.
Timepoint [1] 244789 0
3.5 months following commencement of treatment.

Eligibility
Key inclusion criteria
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) </= 1.5; Serum creatinine </= 200 µmol/L; Serum Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) </= 2.5 x Upper Limit of Normal (ULN) (</= 5 x ULN if due to underlying malignancy); Serum bilirubin </= 35 µmol/L
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 </= 150mmHg and diastolic blood pressure </= 90mmHg (it is acceptable to initiate antihypertensive treatment prior to registration to achieve these goals).
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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
N/A - Nonrandomised Trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A - Nonrandomised Trial.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase II
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
10/09/2010
Actual
10/09/2010
Date of last participant enrolment
Anticipated
Actual
30/08/2012
Date of last data collection
Anticipated
Actual
Sample size
Target
55
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,TAS
Recruitment postcode(s) [1] 1891 0
2050, 2137, 2031, 3081, 3355, 3690, 3144, 5042, 6160, 3199, 2444, 4102, 7000, 0800, 2065, 3065, 3181

Funding & Sponsors
Funding source category [1] 237320 0
Other Collaborative groups
Name [1] 237320 0
Australian & New Zealand Urogenital and Prostate Cancer Trials Group Limited (ANZUP)
Country [1] 237320 0
Australia
Funding source category [2] 269997 0
Commercial sector/Industry
Name [2] 269997 0
Novartis Pharmaceuticals Australia Pty Limited
Country [2] 269997 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
NHMRC Clinical Trials Centre
Level 4, Medical Foundation Building
92-94 Parramatta Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 236803 0
None
Name [1] 236803 0
Address [1] 236803 0
Country [1] 236803 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239419 0
Cancer Institute NSW Clinical Research Ethics Committee
Ethics committee address [1] 239419 0
Ethics committee country [1] 239419 0
Australia
Date submitted for ethics approval [1] 239419 0
Approval date [1] 239419 0
10/03/2010
Ethics approval number [1] 239419 0
HREC/09/CIC/31
Ethics committee name [2] 239542 0
SLHD Ethics Review Committee (RPAH Zone)
Ethics committee address [2] 239542 0
Ethics committee country [2] 239542 0
Australia
Date submitted for ethics approval [2] 239542 0
08/07/2013
Approval date [2] 239542 0
03/09/2013
Ethics approval number [2] 239542 0
X13-0179
Ethics committee name [3] 288022 0
Austin Health Human Research Ethics Committee
Victoria Central Ethics
Ethics committee address [3] 288022 0
Ethics committee country [3] 288022 0
Australia
Date submitted for ethics approval [3] 288022 0
Approval date [3] 288022 0
28/04/2010
Ethics approval number [3] 288022 0
HREC Ref: HREC/10/Austin/9
Project No: H2010/03897
Protocol No: ANZUP 0901
Ethics committee name [4] 288023 0
Bellberry Human Research Ethics Committee
Ethics committee address [4] 288023 0
Ethics committee country [4] 288023 0
Australia
Date submitted for ethics approval [4] 288023 0
Approval date [4] 288023 0
25/11/2010
Ethics approval number [4] 288023 0
Application No: 2010-08-168
Ethics committee name [5] 288024 0
Cabrini Human Research Ethics Committees
Ethics committee address [5] 288024 0
Ethics committee country [5] 288024 0
Australia
Date submitted for ethics approval [5] 288024 0
Approval date [5] 288024 0
28/10/2010
Ethics approval number [5] 288024 0
02-20-09-10
Ethics committee name [6] 288025 0
Flinders Medical Centre Human Research Ethics Committee
Ethics committee address [6] 288025 0
Ethics committee country [6] 288025 0
Australia
Date submitted for ethics approval [6] 288025 0
Approval date [6] 288025 0
20/10/2010
Ethics approval number [6] 288025 0
Application No: 155/10
Ethics committee name [7] 288026 0
Fremantle Hospital Human Research Ethics Committee
Ethics committee address [7] 288026 0
Ethics committee country [7] 288026 0
Australia
Date submitted for ethics approval [7] 288026 0
Approval date [7] 288026 0
10/05/2010
Ethics approval number [7] 288026 0
Ref: 10/102
Ethics committee name [8] 288027 0
Metro South Human Research Ethics Committee
Ethics committee address [8] 288027 0
Ethics committee country [8] 288027 0
Australia
Date submitted for ethics approval [8] 288027 0
Approval date [8] 288027 0
03/09/2010
Ethics approval number [8] 288027 0
HREC Reference No: HREC/10/QPAH/060
Ethics committee name [9] 288028 0
Human Research Ethics Committee of NT Department of Health and Menzies School of Health Research
Ethics committee address [9] 288028 0
Ethics committee country [9] 288028 0
Australia
Date submitted for ethics approval [9] 288028 0
Approval date [9] 288028 0
24/03/2011
Ethics approval number [9] 288028 0
Ref: 11-1505
Ethics committee name [10] 288029 0
Human Research Ethics Committee (Tasmania) Network
Ethics committee address [10] 288029 0
Ethics committee country [10] 288029 0
Australia
Date submitted for ethics approval [10] 288029 0
Approval date [10] 288029 0
05/05/2010
Ethics approval number [10] 288029 0
Ref No: H11083

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29890 0
Prof Ian Davis
Address 29890 0
c/o NHMRC Clinical Trials Centre
Locked Bag 77
Camperdown NSW 1450
Country 29890 0
Australia
Phone 29890 0
+61 2 9562 5000
Fax 29890 0
Email 29890 0
eversun@ctc.usyd.edu.au
Contact person for public queries
Name 13137 0
EVERSUN Trial Coordinator
Address 13137 0
NHMRC Clinical Trials Centre Level 2 8-10 Mallett Street Camperdown NSW 2050
Country 13137 0
Australia
Phone 13137 0
+61 2 9562 5000
Fax 13137 0
+61 2 9562 5094
Email 13137 0
eversun@ctc.usyd.edu.au
Contact person for scientific queries
Name 4065 0
EVERSUN Trial Coordinator
Address 4065 0
NHMRC Clinical Trials Centre Level 2 8-10 Mallett Street Camperdown NSW 2050
Country 4065 0
Australia
Phone 4065 0
+61 2 9562 5000
Fax 4065 0
+61 2 9562 5094
Email 4065 0
eversun@ctc.usyd.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma.2015https://dx.doi.org/10.1093/annonc/mdv078
N.B. These documents automatically identified may not have been verified by the study sponsor.