Clinical trial to assess the importance of nephrectomy

ISRCTN	ISRCTN19562321
DOI	https://doi.org/10.1186/ISRCTN19562321
ClinicalTrials.gov (NCT)	NCT00930033
Protocol serial number	P_070144
Sponsor	NHS Greater Glagsow and Clyde (UK)
Funders	Cancer Research UK's CTAAC Committee (UK), National Cancer Research Network (NCRN) (UK)

Submission date: 21/09/2011
Registration date: 03/11/2011
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-comparing-combination-surgery-sunitinib-kidney-cancer-carmena

Contact information

Prof Arnaud Mejean
Scientific

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

Study information

Primary study design	Interventional
Study design	International multi-centre non-inferiority randomised phase III trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Randomized phase III trial evaluating the importance of nephrectomy in patients presenting with metastatic renal cell carcinoma treated with sunitinib
Study acronym	CARMENA
Study objectives	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(s)	West of Scotland REC 1, Glasgow, 20/12/2010 (re-issued 18/01/2011), ref: 10/S0703/66
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Sunitinib
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	26/05/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1134
Total final enrolment	450
Key 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
Key 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)]
Date of first enrolment	26/05/2011
Date of final enrolment	25/08/2014

Locations

Countries of recruitment

United Kingdom
France
Greece
Norway
Poland

Study participating centre

Hopital Europeen Georges Pompidou (HEGP)

Paris
75908
France

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	02/08/2018	10/04/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			14/10/2020	No	Yes

Editorial Notes

25/10/2022: Internal review.
14/10/2020: Cancer Research UK lay results summary link added to Results (plain English).
16/01/2020: The following changes have been made:
1. The intention to publish date has been added.
2. The total final enrolment number has been added.
10/04/2019: Publication reference added.
09/08/2017: No publications found in PubMed, verifying study status with principal investigator.