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”

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

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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

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

Primary Measures

• The primary endpoint is overall survival.
  • Time Frame: starting at 4 months
    Safety Issue?: Yes

Secondary Measures

• Objective Response (complete or partial) is evaluated according to RECIST 1.1 criteria
  • Time Frame: Starting at 4 months
    Safety Issue?: Yes
• Clinical benefit (complete response, partial or stable for at least 12 weeks).
  • Time Frame: Starting at 4 months
    Safety Issue?: Yes
• Progression-Free Survival
  • Time Frame: Starting at 4 months
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• 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
    Safety Issue?: Yes
• Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy
  • Time Frame: Starting at 4 months
    Safety Issue?: Yes

Inclusion Criteria:

• Age ≥ 18 year
• 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 accessible to nephrectomy (partial or total), according to the patient's surgical urologist. Patients presenting with an inferior vena cava thrombosis can be included.
• Patients for which the indication of Sutent is considered according to the recommendations rules given by national health authorities of participating countries. The prescription of Sutent in the circumstances of the study is considered as a standard treatment.
• Platelets > or = 100 x 109/L, hemoglobin > 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 exams are concerned.
• Life expectancy ≥ 3 months
• Affiliated with social security health insurance
• Written informed consent

Exclusion Criteria:

• Prior systemic treatment for kidney cancer (including Anti angiogenic)
• Bilateral kidney cancer
• Pregnant or breast feeding women
• Non stabilised coronaropathy or episode of myocardial infarction or severe or unstable angora 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
• Anticoagulants with curative intent
• Medical, general or psychiatrics difficulties non compatibles with the study
• Brain metastases
• Prior radiotherapy for kidney cancer
• Previous history of gastric disease or of the small intestine, syndrome of insufficient absorption 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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Assistance Publique - Hôpitaux de Paris Other

Overall Clinical Trial Officials and Contacts

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

Overall Contact: Arnaud Mejean, MD, PhD +33(0)1 44 49 53 36 arnaud.mejean@nck.aphp.fr

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00930033

Study ID Number: P070144

ClinicalTrials.gov Identifier: NCT00930033

Health Authority: France: Ministry of Health