kidney cancer renal cell carinoma
Conditions
Interventions
Arm A will undergo immediate nephrectomy followed by standard medical treatment
for metastatic renal cell carcinoma and compared to arm B in which nephrectomy
is deferred until after 3 courses of st
Sponsors
European Organisation for Research in Treatment of Cancer (EORTC)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histologically confirmed metastatic Renal Cell Cancer of clear-cell subtype with a resectable asymptomatic in situ primary. - Metastatic RCC (mRCC): metastases are not completely resectable at the time of surgery or during an additional intervention. Multiple lesions at one site will make the patient not eligible for complete resection. - Histology *clear-cell* subtype: If the diagnosis is not established patients need to undergo a transcutaneous tru-cut needle biopsy of the primary tumor. - Resectable tumor: primary tumor must be resectable and resectability should not be doubtful at entry. Patients with distant metastases and bulky locoregional lymph node metastases larger than the primary tumor can be included if resectability of the lymph nodes is surgically feasible. - Asymptomatic primary: is defined as the absence of symptoms which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion. As para-neoplastic symptoms cannot be assigned to the primary tumor alone in metastatic disease, they are not included in this definition. - Patients who will receive Sunitinib (Sutent®) as background therapy. - Measurable disease according to RECIST 1.1 criteria. - Prior therapies: - Prior systemic therapy for metastatic RCC is not allowed - Prior local radiotherapy for bone lesions is allowed - Concomitant medications: - Investigational or systemic therapy for metastatic RCC must not be used during the period of protocol treatment. - No systemic corticosteroid and/ or other immunosuppressive systemic therapies - Age * 18 years. - Life expectancy > 3 months. - WHO performance status 0 or 1. - Adequate bone marrow function (Leucocytes > 3.0 x 109/l, platelets >100 x 109/l, hemoglobin > 6.0 mmol/l or > 10.0 g/dL.) - Prothrombin time (PT) or international normalized ratio (INR) * 1.2 x upper limit of normal (ULN). - Partial thromboplastin time (PTT) * 1.2 x ULN. - Adequate hepatic function (bilirubin * 1.5 x ULN, SGPT/ALT * 2.5 x ULN or * 5 x ULN if liver lesions). - Serum calcium 30 ml/min. - Clinically normal cardiac function based on the institutional lower limit of normal LVEF assessed by MUGA or ECHO and normal 12 lead ECG. - Patients with any history of malignancies who are disease-free for more than 5 years are eligible. - Women must be post-menopausal with a total cessation of menses of >1 year, or if of childbearing potential must not be pregnant (negative serum pregnancy test at entry) or lactating; and must agree to use effective contraceptive methods (with a documented failure rate < 1% e.g.; vasectomized partner sterile prior to trial entry and sole sexual partner or double-barrier contraception) from 2 weeks before to enrollment. The duration of the contraception will depend on the treatment that patient will receive. - Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial. - Before patient randomization, written informed consent must be given according
Exclusion criteria
Exclusion criteria: - Patients for whom complete surgical remission can be achieved by removing metastatic sites at nephrectomy or during an additional intervention. - Patients with symptomatic primary necessitating nephrectomy. - Patients with previous partial or total nephrectomy. - Patients with unresectable bulky locoregional lymph node metastases larger than the primary tumor. - Patients with only bone metastases. - Patients having more than 3 of the following surgical risk factors will not be eligible: - serum albumin CTCAE v4.0 grade 2 or worse - serum LDH > 1.5 x UNL - liver metastases - symptoms at presentation due to mestastases - retroperitoneal lymph node involvement - supra-diaphragmatic lymph node involvement - clinical stage T3 or T4 - Patients with serious cardiac illness (myocardial infarction and/or (un)treatable angina pectoris not responding to treatment) within the past 12 months. - Uncontrolled high blood pressure (BP) defined as BP * 150/100 mm Hg despite optimal medical therapy. - Clinical signs of CNS involvement. - Current pulmonary disease. - Patients with active or uncontrolled infections or with serious illnesses, malabsorption syndrome or medical conditions, including patients with a history of chronic alcohol abuse, hepatitis, HIV and/or cirrhosis. - History, within the past five years, of malignancies other than renal cell carcinoma (except: basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score * 6 and postoperative PSA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The duration of progression free survival: the time interval between the date of randomization and the first date of progression (local or distant) or death due to any cause. Progression will be defined according to the RECIST 1.1. In case the patient is still alive without progression, the date of progression/death will be censored at the date of last follow up. In case of early progression within 4 weeks after surgery, the actual date of progression (if confirmed) will be at week 16 in the immediate arm and week 28 in the deferred arm (see Protocol sections 7.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| * Overall survival * Morbidity * Overall response to treatment in the deferred nephrectomy arm including the proportion of patients who become unresectable * Effect of nephrectomy on early progression in both arms | — |
Countries
Netherlands
Outcome results
None listed