111 trial

• Research type

  Research Study

• Full title

  A single group trial evaluating one cycle of adjuvant BEP chemotherapy in high risk, stage 1 non-seminomatous germ cell tumours of the testis (NSGCTT).

• IRAS ID

  1866

• Contact name

  Mike Cullen

• Sponsor organisation

  The Institute of Cancer Research

• Eudract number

  2008-006295-29

• ISRCTN Number

  37875250

• Research summary

  The 111 study is a single group multi-centre study evaluating a single cycle of BEP (bleomycin, etoposide and cisplatin) as adjuvant chemotherapy in high risk, stage 1 non-seminomatous germ cell tumours of the testis (NSGCTT). Data from a previous single group UK trial (reference no. 1) of two cycles of BEP chemotherapy suggest two year recurrence-free survival of 98% in high-risk stage 1 NSGCTT. This study was able to exclude a true recurrence rate of more than 5%. BEPx2 is now standard practice in many parts of the world. Some data suggest that a single chemotherapy cycle might be as effective but the evidence is not strong enough to change practice. The proposed study would add significantly to this data. The aim is to show that one cycle of adjuvant BEP chemotherapy results in a two year recurrence rate of less than 5% in patients with high-risk (vascular invasion positive) stage 1 NSGCTT. Halving the number of chemotherapy cycles given is also expected to reduce short- and long-term toxicity allowing young men to return to normal life more quickly. It would also reduce the overall burden of chemotherapy and healthcare resource usage. The minimum sample size is 236 patients. Events will be closely monitored and the trial terminated should the predicted recurrence risk equal or exceed 5%. Reference 1: Cullen MH, Stenning SP, Parkinson MC, et al. Short course adjuvant chemotherapy in high-risk stage 1 non-seminomatous germ cell tumours of the testis: a Medical Research Council report. J Clin Oncol 1996, vol. 14; 4: 1106-1113

  Summary of study results:

  236 men joined the 111 trial between February 2010 and March 2014 and received one cycle of BEP chemotherapy. These participants came from 33 NHS hospitals across the UK.

  How well did one cycle of BEP work?
  We found that within two years after treatment three participants’ cancer returned. This meant the risk of the cancer coming back within two years after treatment is just over 1 out of 100, which is very similar to the risk after two cycles. So our results show that one cycle of BEP chemotherapy worked as well as two in preventing the cancer from returning. In comparison, cancer returns in about half of all men with this type of cancer who have no chemotherapy following surgery.

  Did the treatments have side effects?
  Many participants had side effects but most often they were mild and/or did not last long. Four out of 10 participants had at least one side effect that was classed as more severe, even though in most cases the patient was unaware there was a problem. These included a drop in white blood cells and blood clotting cells (platelets) or a high temperature typically lasting
  just a few days. A small number of people had longer term side effects but severe effects were relatively rare (reported by 3 out of 100 participants).

  What do these results mean?
  The trial team concluded that one cycle of BEP had similar outcomes as two cycles despite using a much lower total dose of BEP chemotherapy. The results confirm that one cycle of BEP should become a standard treatment for people with early stage testicular cancer when there is a high risk of the cancer returning after the testicle containing the cancer has been removed.

  The full results publication is available at the following web address:
  https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fdoi.org%252F10.1016%252Fj.eururo.2019.11.022%2FNBTI%2FIPK3AQ%2FAQ%2F4a30837e-f408-473b-807d-1c096ce57db8%2F1%2Fk_BG45UBb1&data=05%7C02%7Clondonsoutheast.rec%40hra.nhs.uk%7Ce0eb53f5185443b83af708dcd2499a5a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638616460768509434%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=HmOKFIjYn2feG130e%2FNSkeEcvICUiBCXglCjhegaV34%3D&reserved=0

• REC name

  London - South East Research Ethics Committee

• REC reference

  09/H1102/86

• Date of REC Opinion

  20 Aug 2009

• REC opinion

  Favourable Opinion