TOTEM: Trial of Temsirolimus for Advanced Urothelial Cancer v1.0

• Research type

  Research Study

• Full title

  A Phase I/II single-arm trial to evaluate the combination of cisplatin and gemcitabine with the mTOR inhibitor temsirolimus for first-line treatment of patients with advanced transitional cell carcinoma of the urothelium

• IRAS ID

  1697

• Sponsor organisation

  Cardiff University, Research and Commercial Division

• Eudract number

  2007-007615-82

• ISRCTN Number

  31546330

• Research summary

  The prognosis for patients with advanced urothelial cancer is poor and approximately 4,700 patients in the UK die each year from the disease. Approximately 50% of patients who are fit enough to undergo cisplatin based chemotherapy will respond to treatment. Median progression-free survival for such patients is approximately 8 months, and median overall survival 14 months. Despite a recent increase in our understanding of the molecular basis of bladder cancer, there have been few clinical studies using molecularly-targeted compounds in advanced urothelial cancer.The drug temsirolimus (Torisel©) limits the growth of tumours and has recently been demonstrated to improve survival in advanced renal cancer. Further studies suggest that temsirolimus may have activity against urothelial cancer. This trial aims to assess whether adding temsirolimus to the standard cisplatin/gemcitabine based chemotherapy in the treatment of advanced urothelial cancer is safe and effective for patients with advanced urothelial disease.Up to 99 participants will be administered a maximum of six 21-day cycles of the 3-drug chemotherapy by drip into the arm. The optimum dose for temsirolimus will be determined in the Phase I stage of the trial (up to 42 participants) by dose-escalation in successive cohorts of 3-6 participants, until the maximum tolerated dose (MTD) is met. Once this recommended Phase II dose has been identified, it will be given to an expanded group of participants in Phase II; 63 evaluable participants in total comprising 3-6 from Phase I and 57-60 from Phase II.If results confirm that administration of the 3-drug chemotherapy combination is safe, feasible and sufficiently active, the combination treatment will be taken forward into a randomised trial.

• REC name

  Wales REC 3

• REC reference

  09/MRE09/30

• Date of REC Opinion

  16 Sep 2009

• REC opinion

  Further Information Favourable Opinion