Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery


Condition: Clear-cell Metastatic Renal Cell Carcinoma

Intervention:

  • Drug: sunitinib or pazopanib
  • Procedure: Cytoreductive nephrectomy

Purpose: Two randomized trials in the cytokine era clearly showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC) increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs) including first-line sunitinib and pazopanib in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy. Therefore it is unknown if similar survival benefit could be achieved without CN with these new targeted agents. At the same time there is a need to better understand mechanisms of primary and secondary resistance to TKIs in mRCC patients and to identify eighter prognostic and predictive biomarkers to better define risk factors and potentially druggable targets.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02535351

Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Primary Outcome Measures:

  • Measure: Overall Survival benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs in subjects with mRCC
  • Time Frame: 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Progression-free survival (PFS) and response rate (RR) benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs
  • Time Frame: Radiological assessment: every 12 weeks (±1 week) until Progressive disease (up to 12 months) or treatment discontinuation (up to 5 years)
  • Safety Issue:
  • Measure: Safety profile (Adverse events)
  • Time Frame: day 1, every cycle (6 weeks for patients treated with Sunitinib and 4 weeks for patients treated with Pazopanib) until treatment discontinuation (up to 5 years).
  • Safety Issue:

Estimated Enrollment: 270

Study Start Date: November 2015

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum 75 Years
  • Gender: All

Inclusion Criteria:

  • Written informed consent
  • ECOG Performance Status 0-1
  • Favorable or intermediate MSKCC or Heng risk score
  • Biopsy (primary tumour or metastases) confirming the diagnosis of predominantly clear cell RCC
  • Resectable asymptomatic in situ primary (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.)
  • Tumour suitable to nephrectomy in the opinion of the urologist. Patients with Inferior vena cava thrombosis can be included
  • Documented metastatic disease (CT scan or MRI)
  • Life expectancy > or = 24 weeks
  • Up to three different metastatic sites
  • ≥ 3 metastatic lesions
  • Platelets > 100,000/ml
  • Haemoglobin > 9.0 g/dl
  • neutrophils >1,500/mm3
  • Bilirubin < or = 2 mg/dl, except for patients affected by Gilbert's syndrome
  • AST and ALT < or = 2.5 times the UNL
  • Serum albumin > the LNL
  • Patients of childbearing age should use contraceptive methods during the study

Exclusion Criteria:

  • Prior surgery or systemic treatment for mRCC
  • Bilateral RCC
  • Brain and liver metastases
  • Non-clear-cell histology
  • Poor prognosis as defined by MSKCC or Heng criteria
  • Documented widespread disease (> or =4 metastatic organ sites)
  • Oligometastatic disease suitable of metastasectomy (<3 lesions confined at one organ site)
  • Symptomatic primary tumour at presentation
  • High surgical risk in the opinion of the urologist
  • Patients with > 3 of the following surgical risk factors are not eligible:
  • Serum albumin CTCAE v 4.0 grade 2 or worse
  • Serum LDH > 1.5 times upper limit of normal
  • Symptoms at presentation due to metastases
  • Clinical stage T4 disease
  • History of malabsorption syndrome
  • Pregnant or breastfeeding women
  • Concomitant cardiac disorders: cardiac failure NYHA> 2; Acute coronary syndrome or myocardial infarction or severe or unstable angina within the last 6 months as well as uncontrolled hypertension (sistolic>160, diastolic>90), arrhytmia requiring treatment (except for beta blockers or digossin)
  • Uncontrolled diabetes
  • Deep phlebitis not treated with LMWH or arterial thrombosis within the last 6 months
  • HIV infection
  • Active infections (> Grade 2 NCI-CTC v.3.0)
  • Other cancer within the previous 5 years (except for in situ skin carcinoma, superficial bladder Ta, Tis, T1 and carcinoma of the cervix or every cancer with curative treatment within 5 years)

Contact:

  • Giuseppe Procopio, MD
  • 00390223904450

Location:

  • Fondazione IRCCS Istituto Nazionale Tumori
  • Milan Mi 20133 Italy

View trial on ClinicalTrials.gov


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