Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00930033
Protocol/serial number
P_070144
Study information
Scientific title
Randomized phase III trial evaluating the importance of nephrectomy in patients presenting with metastatic renal cell carcinoma treated with sunitinib
Acronym
CARMENA
Study hypothesis
We are investigating whether removal of the kidney tumour (known as nephrectomy) is of benefit in patients whose tumour has already spread to other organs (known as metastasis). In the past the standard treatment for many patients with kidney cancer that had spread to other organs was a drug called Interferon. In some patients who were treated with Interferon removing the kidney containing the tumour was shown to improve the length of time patients survived. New drugs (like Sunitnib) are now available for the treatment of kidney cancer which have been shown to be much more effective than Interferon and we do not know if removing the kidney is still of benefit to patients. If nephrectomy is no longer needed this would avoid a major operation. The purpose of this study is to see if nephrectomy is of benefit in patients receiving Sunitinib who have a tumour in their kidney with metastasis at the time of diagnosis.
Ethics approval
West of Scotland REC 1, Glasgow, 20/12/2010 (re-issued 18/01/2011), ref: 10/S0703/66
Study design
International multi-centre non-inferiority randomised phase III trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Metastatic renal cell carcinoma, clear cell carcinoma (the most common type of renal cell carcinoma).
Intervention
Treatment Arms:
Arm A: Nephrectomy followed by Sunitinib
Arm B: Sunitinib alone
Sunitinib will be administered orally daily for 4 weeks followed by a 2 week rest (4/2 schedule). A cycle is considered 6 weeks. Sunitinib starting dose is 50 mg daily with provision for dose reduction based on tolerability. Patients will be treated until disease progression, occurrence of unacceptable toxicity or withdrawal.
For patients randomised to Arm A (nephrectomy plus Sunitinib):
1. The time between randomisation and nephrectomy should not exceed 28 days.
2. Treatment with Sunitinib will be started, as far as possible, between the 3rd week and the end of the 6th week following nephrectomy.
For patients randomised to Arm B (Sunitinib alone):
1. Sunitinib will be started within the 21 days following randomisation.
2. Sunitinib will be administered in 28 day cycles separated by 2 weeks off (4/2 schedule)
Intervention type
Drug
Phase
Phase III
Drug names
Sunitinib
Primary outcome measure
To evaluate the importance of initial nephrectomy for the subsequent survival of patients with metastatic renal cell carcinoma treated with sunitinib. This is calculated by the time between the date of randomisation and the date of death, irrespective of cause of death.
Secondary outcome measures
1. Tumour response
2. Progression free survival- Progression-free survival is calculated by the time between the date of randomisation and the date of progression or the date of initiating second-line treatment. Patients who have died from other causes are recorded on the date of death. Patients who are alive and progression-free when last heard of are recorded on the date of the last visit.
3. The percentage of patients who cannot start Sunitinib treatment within 6 weeks postoperatively on Arm A (nephrectomy + Sunitinib)
4. The need to perform nephrectomy in Arm B (Sunitinib alone)
5. Postoperative morbidity is evaluated using the Clavien scales
6. Postoperative mortality is evaluated by the percentage of deaths within the 30 days following nephrectomy.
7. Tolerability, particularly changes in renal function over time is evaluated by the NCI-CTC v3 scales
Overall trial start date
01/08/2009
Overall trial end date
26/05/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age ≥ 18 years
2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
3. Biopsy (primary tumour or metastases) confirming the diagnosis of clear cell carcinoma alone or preponderant
4. Documented metastatic disease
5. Absence of prior systemic treatment for kidney cancer including anti angiogenic (AA)
6. Tumour amenable to nephrectomy (partial or total) in the opinion of the patients urologist. Patients presenting with an inferior vena cava thrombosis can be included.
7. Patients for which the indication of Sunitinib is considered according to the recommendations rules given by national health authorities of participating countries. The prescription of Sunitinib in the circumstances of the study is considered as a standard treatment
8. Platelets 100 x 109/L, haemoglobin > 9 g/dl, neutrophils >1.5 x 109/L
9. Bilirubin < 2 mg/dL, aspartate transaminase (ASAT) and alanine transaminase (ALAT), 2.5 times the upper normal limit (UNL) or 5 times UNL for patients with liver metastases
10. Patients of child bearing age should use contraceptive methods
11. Patient able to follow the procedures outlined in the protocol as far as the planning of visits and examinations are concerned
12. Life expectancy ≥ 3 months
13. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1134
Participant exclusion criteria
1. Prior systemic treatment for kidney cancer (including anti angiogenic)
2. Bilateral kidney cancer
3. Pregnant or breast feeding women
4. Acute coronary syndrome or episode of myocardial infarction or severe or unstable angina within the last 6 months as well as severe diabetes with severe peripheral arteriopathy or deep phlebitis or arterial thrombosis within the last 3 months
5. Anticoagulant therapy in treatment dose
6. Medical, general or psychiatric difficulties which, in the opinion of the Investigator, would make it inappropriate for trial entry
7. Brain metastases
8. Previous history of gastric disease or of malabsorption compromising the absorption of Sunitinib
9. Experimental treatment within the 28 days preceding inclusion
10. Other cancer within the previous 5 years [except for insitu skin carcinoma and treated localised prostate cancer with undetectable Prostate-specific antigen (PSA)]
Recruitment start date
26/05/2011
Recruitment end date
25/08/2014
Locations
Countries of recruitment
France, Greece, Norway, Poland, United Kingdom
Trial participating centre
Hopital Europeen Georges Pompidou (HEGP)
Paris
75908
France
Sponsor information
Organisation
NHS Greater Glagsow and Clyde (UK)
Sponsor details
c/o Dr Nathaniel Brittain
Research and Development Central Office
The Tennent Institute
1st Floor
Western Infirmary
38 Church Street
Glasgow
G11 6NT
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK's CTAAC Committee (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
National Cancer Research Network (NCRN) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list