Clinical Trial to Assess the Importance of Nephrectomy (CARMENA)

• ClinicalTrials.gov Identifier: NCT00930033
• Recruitment Status: Completed
• First Posted: June 30, 2009
• Last Update Posted: April 14, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborator: Pfizer
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: June 29, 2009
• First Posted Date: June 30, 2009
• Last Update Posted Date: April 14, 2021
• Actual Study Start Date: September 9, 2009
• Actual Primary Completion Date: October 22, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 29, 2009): The primary endpoint is overall survival. [ Time Frame: starting at 4 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 21, 2011)

• Objective Response (complete or partial) is evaluated according to RECIST 1.1 criteria [ Time Frame: Starting at 4 months ]
• Clinical benefit (complete response, partial or stable for at least 12 weeks). [ Time Frame: Starting at 4 months ]
• Progression-Free Survival [ Time Frame: 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 [ Time Frame: Starting at 4 months ]
• Non-compliance to sunitinib treatment is evaluated in arm B (sunitinib alone) as the percentage of patients needing nephrectomy [ Time Frame: Starting at 4 months ]
• Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy [ Time Frame: Starting at 4 months ]

Original Secondary Outcome Measures (submitted: June 29, 2009)

• Objective Response (complete or partial) is evaluated according to RECIST criteria [ Time Frame: Starting at 4 months ]
• Clinical benefit (complete response, partial or stable for at least 12 weeks). [ Time Frame: Starting at 4 months ]
• Progression-Free Survival [ Time Frame: 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 [ Time Frame: Starting at 4 months ]
• Non-compliance to sunitinib treatment is evaluated in arm B (sunitinib alone) as the percentage of patients needing nephrectomy [ Time Frame: Starting at 4 months ]
• Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy [ Time Frame: Starting at 4 months ]
• Tolerance is evaluated according to NCI-CTC v3. [ Time Frame: Starting at 4 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical Trial to Assess the Importance of Nephrectomy
• Official Title: Randomized Phase III Trial Evaluating the Importance of Nephrectomy in Patients Presenting With Metastatic Renal Cell Carcinoma Treated With Sunitinib
• Brief Summary: 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

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Renal Cell Carcinoma

Intervention

• Procedure: Nephrectomy
  Current surgery
• Other: Sunitinib alone
  Sunitinib alone without nephrectomy
  Other Name: Sunitinib alone without nephrectomy

Study Arms

• Active Comparator: A
  Nephrectomy + sunitinib
  Intervention: Procedure: Nephrectomy
• Experimental: B
  Sunitinib alone
  Intervention: Other: Sunitinib alone

Publications *

• 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. Erratum In: Target Oncol. 2014 Jun;9(2):181. Garcia-Figueras, Roberto [corrected to Garcia-Figueiras, Roberto].

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 6, 2017): 452
• Original Estimated Enrollment (submitted: June 29, 2009): 576
• Actual Study Completion Date: October 22, 2018
• Actual Primary Completion Date: October 22, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00930033
• Other Study ID Numbers: P070144
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Zakia Idir, Department Clinical Research of Developpement
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Pfizer

Investigators

• Principal Investigator: Arnaud Mejean, MD PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: April 2021