Randomized Phase III trial comparing immediate versus deferred nephrectomy in patients with synchronous metastatic renal cell carcinoma. EORTC 30073 SURTIME
- Conditions
- kidney cancerrenal cell carinoma1003836410038365
- Registration Number
- NL-OMON34814
- Lead Sponsor
- European Organisation for Research in Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 147
- 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 < 10.0 mg/dL.
- Adequate renal function: calculated or measured clearance creatinine >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
- 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 < 0.5 ng/ml).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The duration of progression free survival: the time interval between the date<br /><br>of randomization and the first date of progression (local or distant) or death<br /><br>due to any cause. Progression will be defined according to the RECIST 1.1. In<br /><br>case the patient is still alive without progression, the date of<br /><br>progression/death will be censored at the date of last follow up.<br /><br>In case of early progression within 4 weeks after surgery, the actual date of<br /><br>progression (if confirmed) will be at week 16 in the immediate arm and week 28<br /><br>in the deferred arm (see Protocol sections 7.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Overall survival<br /><br>* Morbidity<br /><br>* Overall response to treatment in the deferred nephrectomy arm including the<br /><br>proportion of patients who become unresectable<br /><br>* Effect of nephrectomy on early progression in both arms</p><br>