Condition category
Cancer
Date applied
21/09/2011
Date assigned
03/11/2011
Last edited
11/05/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Arnaud Mejean

ORCID ID

Contact details

Department of Urology Necker
Hopital Europeen Georges Pompidou (HEGP)
20 Rue Leblanc
Paris
75908
France

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 measures

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

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 patient’s 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

http://www.nhsggc.org.uk/content/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes