Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

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

Methods and analysis

Suitable patients will have histologically/cytologically confirmed, stage III NSCLC and are able to undergo chemoradiotherapy treatment. The study will recruit 360 patients; 120 on the standard arm and 60 on each experimental arm. Patients will complete 2–4 cycles of platinum-based chemotherapy before being randomised to one of the radiotherapy schedules. The primary endpoint is progression-free survival, with overall survival, time to local–regional failure, toxicity and cost-effectiveness as secondary objectives.

Ethics and dissemination

The study has received ethical approval (research ethics committee (REC) reference: 16/WS/0165) from the West of Scotland REC 1. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial results will be published in a peer-reviewed journal and presented internationally.

Trial registration number

ISRCTN47674500.

Related collections

Most cited references 13

Record: found
Abstract: found
Article: not found

Guidelines on the radical management of patients with lung cancer.

Eric Lim, David Raymond Baldwin, Michael A. Beckles … (2010)

A joint initiative by the British Thoracic Society and the Society for Cardiothoracic Surgery in Great Britain and Ireland was undertaken to update the 2001 guidelines for the selection and assessment of patients with lung cancer who can potentially be managed by radical treatment.

0 comments Cited 100 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Design issues of randomized phase II trials and a proposal for phase II screening trials.

B Freidlin, S. Percy Ivy, Lawrence Rubinstein … (2005)

Future progress in improving cancer therapy can be expedited by better prioritization of new treatments for phase III evaluation. Historically, phase II trials have been key components in the prioritization process. There has been a long-standing interest in using phase II trials with randomization against a standard-treatment control arm or an additional experimental arm to provide greater assurance than afforded by comparison to historic controls that the new agent or regimen is promising and warrants further evaluation. Relevant trial designs that have been developed and utilized include phase II selection designs, randomized phase II designs that include a reference standard-treatment control arm, and phase II/III designs. We present our own explorations into the possibilities of developing "phase II screening trials," in which preliminary and nondefinitive randomized comparisons of experimental regimens to standard treatments are made (preferably using an intermediate end point) by carefully adjusting the false-positive error rates (alpha or type I error) and false-negative error rates (beta or type II error), so that the targeted treatment benefit may be appropriate while the sample size remains restricted. If the ability to conduct a definitive phase III trial can be protected, and if investigators feel that by judicious choice of false-positive probability and false-negative probability and magnitude of targeted treatment effect they can appropriately balance the conflicting demands of screening out useless regimens versus reliably detecting useful ones, the phase II screening trial design may be appropriate to apply.

0 comments Cited 100 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

Audrey Mauguen, Cecile Le Pechoux, Michele I Saunders … (2012)

Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.

0 comments Cited 62 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2019

Publication date (Electronic): 29 January 2019

Volume: 9

Issue: 1

Electronic Location Identifier: e019903

Affiliations

[1 ] departmentDepartment of Clinical Oncology , Weston Park Hospital , Sheffield, UK

[2 ] departmentCancer Research UK Clinical Trials Unit, Institute of Cancer Sciences , University of Glasgow , Glasgow, UK

[3 ] departmentDivision of Cancer Sciences , University of Manchester , Manchester, UK

[4 ] Guy’s & St. Thomas’ NHS Trust, Guy’s Hospital , London, UK

[5 ] Velindre Cancer Centre , Cardiff, UK

[6 ] departmentDepartment of Physics , Clatterbridge Cancer Centre , Bebington, UK

[7 ] National Radiotherapy Trials Quality Assurance (RTTQA) Group, Mount Vernon Hospital , Middlesex, UK

[8 ] departmentHealth Economics and Health Technology Assessment , Institute of Health and Wellbeing, University of Glasgow , Glasgow, UK

[9 ] National Cancer Research Institute Consumer Liaison Group , London, UK

Author notes

[Correspondence to ] Dr Matthew Q F Hatton; matthew.hatton@ 123456sth.nhs.uk

Author information

Corinne Faivre-Finn http://orcid.org/0000-0001-5617-9781

Article

Publisher ID: bmjopen-2017-019903

DOI: 10.1136/bmjopen-2017-019903

PMC ID: 6352760

PubMed ID: 30700475

SO-VID: 99d0fc7a-b374-4ba0-96f1-43d90d8d7f26

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

History

Date received : 24 October 2017

Date revision received : 23 July 2018

Date accepted : 05 November 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000289, Cancer Research UK;

Custom metadata

special-feature unlocked

ScienceOpen disciplines: Medicine

Keywords: non-small cell lung cancer,sequential,chemo-radiotherapy,radiotherapy

Data availability:

ScienceOpen disciplines: Medicine

Keywords: non-small cell lung cancer, sequential, chemo-radiotherapy, radiotherapy

Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study

Read this article at

Abstract

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Related collections

Inflamed lung in vitro co-culture models

Most cited references 13

Guidelines on the radical management of patients with lung cancer.

Design issues of randomized phase II trials and a proposal for phase II screening trials.

Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 569

Cited by 5

Most referenced authors 279