A Phase II Study Of Prenephrectomy Everolimus In Metastatic RCC

• Research type

  Research Study

• Full title

  A Phase I Study Of Everolimus Therapy Before Nephrectomy In Metastatic Renal Cell Cancer

• IRAS ID

  21544

• Contact name

  james larkin

• Eudract number

  2009-013381-54

• ISRCTN Number

  N/A

• Clinicaltrials.gov Identifier

  N/A

• Research summary

  Summary of Research
  Nephrectomy is standard practice in fit patients with metastatic renal cell carcinoma (RCC). Inhibitors of the mammalian target of rapamycin (mTOR) such as everolimus and temsirolimus are active in metastatic renal cell carcinoma but mechanisms of response and resistance to therapy are poorly understood. This is a 'window of opportunity' study in which patients with metastatic RCC due to undergo nephrectomy are treated with everolimus for 6 weeks before surgery and after surgery until they are no longer gaining clinical benefit. The main purpose of the study is to investigate the safety of this approach. Analysis of biomarkers before treatment and on treatment is a further major aim in order to investigate mechanisms of response and resistance.

  Summary of Results
  This study explored the safety of 6 weeks of treatment with Everolimus, a treatment already licensed for metastatic kidney cancer, to patients before nephrectomy surgery (kidney removal) for clear cell renal cell carcinoma.
  The secondary objectives were to assess toxicity, response to treatment, progression free and overall survival.
  In addition, it aimed to explore changes in biomarkers in the blood with toxicity, response to treatment and survival. It also aimed to explore changes in the tumour on functional magnetic resonance imaging (MRI) before and after 6 weeks of Everolimus, and at disease progression. Due to changes in the treatment landscape, it was deemed unethical to continue recruitment and the trial was ended early. The study did not meet its recruitment target, only recruiting 7 patients out of the planned 40. Statistical analysis of the results was therefore not performed.
  All 7 patients discontinued treatment due to disease progression. Eight serious adverse events (SAE) were observed across the 7 patients, with five felt to be unrelated to the study drug. Two were grade 2, five were grade 3 and two were grade 4. Only one SAE was related to the study drug – grade 3 pneumonitis (lung inflammation).
  This study did not collect enough evidence to support the safety and/or efficacy of Everolimus pre-operatively in metastatic clear cell renal cell carcinoma. It is therefore not recommended in this setting.

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  09/H0801/96

• Date of REC Opinion

  1 Dec 2009

• REC opinion

  Favourable Opinion