CARMENA: Clinical Trial to Assess the Importance of Nephrectomy

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00930033

Collaborator

Pfizer (Industry)

452

Enrollment

Location

Arms

109.4

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Procedure: Nephrectomy Other: Sunitinib alone	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

452 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 9, 2009

Actual Primary Completion Date :

Oct 22, 2018

Actual Study Completion Date :

Oct 22, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The primary endpoint is overall survival. [starting at 4 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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