Clinical Trial to Assess the Importance of Nephrectomy (CARMENA)

Randomized Phase III Trial Evaluating the Importance of Nephrectomy in Patients Presenting With Metastatic Renal Cell Carcinoma Treated With Sunitinib

The study compare the standard treatment with nephrectomy + sunitinib to treatment with sunitinib alone without nephrectomy. This study will be the first trial on this competitive context

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Procedure: Nephrectomy; Other: Sunitinib alone

Detailed Description

The 2 previous studies on the impact of nephrectomy (EORTC, SWOG) in metastatic renal cell carcinoma have justified recommendation to initial nephrectomy for patients presenting with metastatic renal cell carcinoma. But these studies were performed at the time of immunotherapy.

The objective is Evaluation of the importance of nephrectomy in patients with metastatic renal cell carcinoma treated with sunitinib (AA) Arm A : Nephrectomy followed by Sunitinib Arm B : Sunitinib alone Sunitinib will be administrated orally daily for 4 weeks followed by a 2 week rest( schedule 4/2), 6 weeks are considered as a cycle The starting dose will be 50 mg daily with provision for dose reduction based on tolerability Patient will be treated until disease progression or unacceptable toxicity occurrence or withdraw.

• Study Type: Interventional
• Enrollment (Actual): 452
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hopital Necker

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age ≥ 18 years
• ECOG Performance Status 0 - 1
• Biopsy (primary tumour or metastases) confirming the diagnosis of clear cell carcinoma
• Documented metastatic disease
• Absence of prior systemic treatment for kidney cancer including AA
• 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.
• 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.
• Platelets > or = 100 x 109/L, haemoglobin >or = 9 g/dl, neutrophils >or = 1.5 x 109/L;
• Bilirubin < or = 2 mg/dL, aspartate transaminase (ASAT) and alanine transaminase (ALAT)< or = 2.5 times the upper normal limit (UNL) or < or = 5 times UNL for patients with liver metastases
• Patients of child bearing age should use contraceptive methods
• Patient able to follow the procedures outlined in the protocol as far as the planning of visits and examinations are concerned.
• Life expectancy ≥ 3 months
• Written informed consent
• Patient without brain metastases or with radiotherapy or surgery treated brain metastases without progression into 6 weeks and non treated by corticoid
• Patient non treated by anticoagulants excepted HBPM

Exclusion Criteria:

• Prior systemic treatment for kidney cancer (including Anti Angiogenic)
• Bilateral kidney cancer
• Pregnant or breast feeding women
• 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 not treated with low molecular weight heparin or arterial thrombosis within the last 3 months
• Patients being treated with antivitamin K with curative intent (please note that patients being treated with low molecular weight heparin can be included)
• Medical, general or psychiatric difficulties which, in the opinion of the Investigator, would make it inappropriate for trial entry
• Symptomatic or untreated brain metastases (patients with brain metastases that have been treated by radiotherapy or surgery and have stable disease within 6 weeks, and are not requiring treatment with corticosteroids can be included)
• Previous history of gastric disease or malabsorption, syndrome compromising the absorption of Sunitinib
• Experimental treatment within the 28 days preceding inclusion
• Other cancer within the previous 5 years (except for insitu skin carcinoma and treated localised prostate cancer with undetectable PSA)
• Patient has received treatment with IV biphosphonate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Nephrectomy + sunitinib	Procedure: Nephrectomy; Current surgery
Experimental: B; Sunitinib alone	Other: Sunitinib alone; Sunitinib alone without nephrectomy; Other Names: Sunitinib alone without nephrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint is overall survival.	starting at 4 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response (complete or partial) is evaluated according to RECIST 1.1 criteria	Starting at 4 months
Clinical benefit (complete response, partial or stable for at least 12 weeks).	Starting at 4 months
Progression-Free Survival	Starting at 4 months
Non-compliance to Sunitinib treatment is evaluated in arm A (nephrectomy + sunitinib) as the percentage of patients not starting sunitinib treatment within 6 weeks after nephrectomy	Starting at 4 months
Non-compliance to sunitinib treatment is evaluated in arm B (sunitinib alone) as the percentage of patients needing nephrectomy	Starting at 4 months
Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy	Starting at 4 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pfizer; Unité de Recherche Clinique Necker Cochin, France
• Investigators: Principal Investigator: Arnaud Mejean, MD PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Mejean A, Ravaud A, Thezenas S, Chevreau C, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Oudard S, Laguerre B, Gross-Goupil M, Bernhard JC, Colas S, Albiges L, Lebret T, Treluyer JM, Timsit MO, Escudier B. Sunitinib Alone or After Nephrectomy for Patients with Metastatic Renal Cell Carcinoma: Is There Still a Role for Cytoreductive Nephrectomy? Eur Urol. 2021 Oct;80(4):417-424. doi: 10.1016/j.eururo.2021.06.009. Epub 2021 Jun 27.
• Mejean A, Ravaud A, Thezenas S, Colas S, Beauval JB, Bensalah K, Geoffrois L, Thiery-Vuillemin A, Cormier L, Lang H, Guy L, Gravis G, Rolland F, Linassier C, Lechevallier E, Beisland C, Aitchison M, Oudard S, Patard JJ, Theodore C, Chevreau C, Laguerre B, Hubert J, Gross-Goupil M, Bernhard JC, Albiges L, Timsit MO, Lebret T, Escudier B. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med. 2018 Aug 2;379(5):417-427. doi: 10.1056/NEJMoa1803675. Epub 2018 Jun 3.
• Leon L, Garcia-Figueiras R, Suarez C, Arjonilla A, Puente J, Vargas B, Mendez Vidal MJ, Sebastia C. Recommendations for the clinical and radiological evaluation of response to treatment in metastatic renal cell cancer. Target Oncol. 2014 Mar;9(1):9-24. doi: 10.1007/s11523-013-0304-7. Epub 2013 Dec 12.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2009
• Primary Completion (Actual): October 22, 2018
• Study Completion (Actual): October 22, 2018

Study Registration Dates

• First Submitted: June 29, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimated): June 30, 2009

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: sunitinib; Nephrectomy,; metastatic renal cell carcinoma,
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Surgical Procedures, Operative; Azoles; Indoles; Pyrroles; Urologic Surgical Procedures; Urogenital Surgical Procedures; Sunitinib; Nephrectomy
• Other Study ID Numbers: P070144