Clinical trial NCT00930033: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Keywords: Nephrectomy,
metastatic renal cell carcinoma,
sunitinib
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2009-06-30
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The primary endpoint is overall survival.
timeFrame: starting at 4 months
Secondary outcomes:
measure: Objective Response (complete or partial) is evaluated according to RECIST 1.1 criteria
timeFrame: Starting at 4 months
measure: Clinical benefit (complete response, partial or stable for at least 12 weeks).
timeFrame: Starting at 4 months
measure: Progression-Free Survival
timeFrame: Starting at 4 months
measure: 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
timeFrame: Starting at 4 months
measure: Non-compliance to sunitinib treatment is evaluated in arm B (sunitinib alone) as the percentage of patients needing nephrectomy
timeFrame: Starting at 4 months
measure: Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy
timeFrame: Starting at 4 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Necker
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Arnaud Mejean, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.