ADSCaN

• Research type

  Research Study

• Full title

  A Randomised Phase II study of Accelerated, Dose escalated, Sequential Chemo-radiotherapy in Non-Small Cell Lung Cancer

• IRAS ID

  190574

• Contact name

  Matthew Hatton

• Contact email

  matthew.hatton@sth.nhs.uk

• Sponsor organisation

  NHS Greater Glasgow and Clyde

• ISRCTN Number

  ISRCTN47674500

• Duration of Study in the UK

  4 years, 7 months, 1 days

• Research summary

  Research Summary

  Lung cancer is the most common cause of cancer mortality in the UK. NSCLC accounts for approximately 85% of all lung cancers and a third of the patients present with stage III disease. Most patients present with inoperable disease and therefore radiotherapy plays a major role in treatment. However, the majority of patients are not suitable for the gold standard treatment (concurrent chemo-radiotherapy) due to performance status and comorbidities. Consequently novel strategies integrating radiotherapy advances and radiobiological knowledge need to be evaluated in patients treated with sequential chemo-radiotherapy. The UK strategy has been to develop separate dose escalation protocols for accelerated radiotherapy schedules (CHART-ED , IDEAL-CRT, I-START and Isotoxic IMRT. This study will compare these schedules with a UK standard sequential chemo-radiotherapy schedule of 55Gy in 20 fractions over 4 weeks. As it would be impossible to test all schedules in phase III study the aim is to use a combined randomized phase II screening / ‘pick the winner’ approach to identify the best schedule to take into a randomised Phase III study against conventionally fractionated radiotherapy.

  Suitable patients will have histologically / cytologically confirmed, stage III NSCLC and are able to undergo chemo-radiotherapy treatment. The study will recruit 360 patients; 120 patients on the standard arm and 60 on each experimental arm. Patients will complete 3 cycles of a platinum based chemotherapy before being randomised on study to one of the radiotherapy schedules.

  Summary of Results

  Background and Study Aims
  Participants with locally advanced lung cancer are often treated with chemotherapy and high dose radiotherapy when surgery is not an option. This study looked at different radiotherapy treatment schedules for patients with non-small cell lung cancer. In order to try to improve the result of treatment a number of UK trial groups had developed higher dose radiotherapy schedules and tested their safety. Four schedules that increase the radiotherapy dose delivered to the tumour had been developed and previous trials provided the right dose for these schedules (CHART-ED. IDEAL-CRT, I-START and Isotoxic IMRT). The aim of the ADSCaN study was to test these different radiotherapy schedules against each other to see which was most promising, and to compare them to the current UK standard treatment schedule. The ultimate aim was to delay progression for patients with inoperable lung cancer.

  Who carried out the research?
  This study was sponsored by NHS Greater Glasgow and Clyde and funded by Cancer Research UK. The study was co-ordinated by the Cancer Research UK Glasgow Clinical Trials Unit on behalf of NHS Greater Glasgow and Clyde.
  The Chief Investigator was Professor Matthew Hatton, Professor of Oncology at Weston Park Hospital, Sheffield.
  The study included a robust quality assurance programme that was led by the NRCI Radiotherapy Trials QA (RTTQA) group.

  What public involvement was there in the study (how many people, what their relevant lived experience was, and what they did)
  The study had public involvement from the very beginning. The research team included members of the public that that had a good understanding of lung cancer. Their opinion was requested particularly when considering the different types of radiotherapy and the burden that attending for treatment and investigations would have on participants. They also reviewed all documentation that was provided to participants.

  Where and when the study took place
  The study took place in 22 cancer centres throughout the UK from August 2017 to February 2022.

  Who participated in the study?
  Suitable participants were aged 16 or over that had been diagnosed with stage III non-small cell lung cancer, and were able to receive chemo-radiotherapy treatment. The participants received chemotherapy before joining the study to receive radiotherapy.

  What treatments or interventions did the participants take/receive?
  Participants had completed between 2-4 cycles of a platinum based chemotherapy before taking part in the study. On the study they were randomised to receive one of five radiotherapy treatment schedules.

  Standard radiotherapy is given over 4 weeks with 20 fractions given on Monday to Friday. The experimental arm radiotherapy courses varied, so the course of radiotherapy treatment in this study was slightly shorter or longer than the standard treatment, lasting between 17 days and 5 weeks in total.

  The difference radiotherapy courses are explained below;

  Standard Arm
  Arm A: Standard: 55Gy in 20 fractions over 26-28 days. (1 session per day over 4 weeks)

  Experimental Arms
  Arm B: CHART-ED: 54Gy, 36 fractions, 12 days then 10.8Gy, 6 fractions (day 15-17)
  (3 sessions per day over 2½ weeks)
  Arm C: IDEAL: Isotoxic radiotherapy 30 fractions, 5 weeks, prescribed dose 63-71Gy (1 session per day over 4 weeks)
  Arm D: I-START: Isotoxic radiotherapy 20 fractions, 4 weeks total dose of 55 – 65 Gy (1 session per day over 4 weeks).
  Arm E: Isotoxic IMRT: Isotoxic regime IMRT, individualised dose escalation 79.2Gy in 1.8Gy over 4 weeks BD (2 sessions per day over 4 weeks).

  What were the results of the study?
  Sadly the study finished early due to funding being stopped by the study funders, meaning it was not possible to complete recruitment and achieve the study targets. The study funders recognised that the study was addressing an important question in comparing 4 different experimental radiotherapy regimens. However they noted there had been some challenges due to a change in practice combined with the impact of the COVID-19 pandemic. They felt study would not be able to achieve its target in a timely manner.

  Details of any further research planned
  At this moment in time there are no plans for further research.

  Where can I learn more about this study?
  A summary of the study results will be written (in English) and published on the Cancer Research UK About Cancer database.
  Information regarding the study is also available on the clinical trial register: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbdFELGNEN9gmUgjOT6gsimibRiULQwKWUOBBMnLTwrfxMDhl_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJuxPskd6R8YiJvOyh-2BKsx8ixlsCcowEIMkQme52YBCGgQtblg2KAIAlFjfgA6GH-2B8Pff4x5pF-2Bi2uf3NuLvcMCRpYqtoa10TOxg6Suo-2FMJplf-2BPYwNr8dxOomnEkg5vA3ESJfxXd5IIs6ZG3mPB5TO-2BIs6hlsnNfUEP2F4RZ-2Br4g-3D-3D&data=05%7C02%7Capprovals%40hra.nhs.uk%7C3f3eff43f2ad4cb3520908dc22740b2b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638423129002329885%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=vfppi1hwdnGZJvjTvZRGZ47hWB8QoIE%2BQu%2BnD2nY8ws%3D&reserved=0

  We would like to thank the participants and their families that took part in this research. And also thank all study investigators and staff from participating hospitals, also the study team and study Sponsor.

• REC name

  West of Scotland REC 1

• REC reference

  16/WS/0165

• Date of REC Opinion

  8 Nov 2016

• REC opinion

  Further Information Favourable Opinion