Phase I study of Continuous Hyperfractionated Accelerated RadioTherapy - Escalated Dose

ISRCTN	ISRCTN45918260
DOI	https://doi.org/10.1186/ISRCTN45918260
Secondary identifying numbers	CHART-ED Version Final 2.0

Submission date: 10/12/2008
Registration date: 03/12/2009
Last edited: 02/09/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-adding-increased-dose-radiation-to-chart-radiotherapy-to-treat-non-small-cell-lung-cancer-chart-ed

Contact information

Dr Matthew Hatton
Scientific

Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom

Email	matthew.hatton@sth.nhs.uk

Study information

Study design	Multicentre phase I feasibility study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A dose escalation phase I study of continuous, hyperfractionated, accelerated radiotherapy (CHART) in patients with inoperable non-small cell lung cancer
Study acronym	CHART-ED
Study hypothesis	The CHART-ED study aims to assess the feasibility of radiotherapy dose-escalation for treating patients with inoperable stage III non-small cell lung cancer (NSCLC). This study is a multicentre phase I feasibility study. Once completed, a randomised phase II comparison of the dose escalated chemo-radiotherapy CHART-ED schedule with a concurrent chemo-radiotherapy protocol is planned. As of 01/03/2011 the anticipated end date for this trial has been updated from 31/12/2009 to 01/09/2011
Ethics approval(s)	Oxfordshire Research Ethics Committee (REC) A on 21/10/2008 (ref: 08/H0604/147)
Condition	Non-small cell lung cancer (NSCLC)
Intervention	Pre-study evaluation: The following baseline assessments need to be performed within the 42 days prior to the radiotherapy planning scan: 1. History (including severity of chronic obstructive airways disease) and examination 2. Respiratory related medication current and previous history 3. All concurrent medication (e.g., statins, angiotensin converting enzyme inhibitor [ACEI], non-steroidal anti-inflammatory drugs [NSAIDs]) 4. Assessment of performance status 5. Assessment of MRC dyspnoea score 7. Chest X-ray (CXR) 8. Positron emission tomography (PET) or co-registered PET-computed tomography (PET-CT) scan 9. CT scan of the thorax and upper abdomen. Either the CT scan and PET scan (or co-registered PET-CT scan) must be performed within 42 days of the radiotherapy (RT) planning scan. 10. Pulmonary function tests (PFTS) - performed within 14 days of the RT planning CT scan: 10.1. Forced expiratory volume in one second (FEV1) 10.2. Forced vital capacity (FVC) 10.3. Carbon monoxide transfer factor (DLCO) corrected for haemoglobin (Hb) level 11. Baseline blood tests: 11.1. Haematology: full blood count 11.2. Biochemistry: renal function, liver function, bone profile 12. Electrocardiogram (ECG) 13. Pregnancy test (if applicable) Interventions: Radiotherapy dose-escalation. Dose escalation schedule: Group 1: 57.6 Gy in 38 fractions, treating 8 hours apart on day 15 Group 2: 61.2 Gy in 40 fractions, treating 8 hours apart on days 15 - 16 Group 3: 64.8 Gy in 42 fractions, treating 8 hours apart on days 15 - 17
Intervention type	Other
Primary outcome measure	The degree of dose escalation achievable. This will be determined by the incidence and grade of potential dose limiting toxicities: 1. Pulmonary toxicity: 1.1. Early radiation pneumonitis (ERTP): occurring within 6 months of finishing RT 1.2. Late radiation pneumonitis (LRTP)/fibrosis: occurring after the six months period following RT 1.3. Changes in pulmonary function tests (PFTs) 2. Oesophageal toxicity: 2.1. Acute oesophagitis: occurring during RT or up to three months post RT 2.2. Chronic oesophagitis/stricture: occurring/persisting beyond three months post-completion of RT 3. Spinal cord toxicity 4. Cardiac toxicity Toxicity will be assessed at the following post-treatment assessments: 1. Weekly until 1 month post-treatment 2. Monthly until 6 months post-treatment 3. Three-monthly until 2 years post-treatment 4. Six-monthly until 3 years post-treatment 5. Annually until 5 years post-treatment
Secondary outcome measures	1. Tumour response 2. Two year survival 3. Overall survival 4. Progression free survival 5. Local control Follow-up visits measuring weight (performance status) and adverse events (dyspnoea score) will occur at the following timepoints: 1. Weekly until 1 month post-treatment 2. Monthly until 6 months post-treatment 3. Three-monthly until 2 years post-treatment 4. Six-monthly until 3 years post-treatment 5. Annually until 5 years post-treatment In addition, the following investigations will be requested: 1. CXR: at months 1, 2, 5, 12, 18, 24 post-treatment 2. CT chest/abdomen: at months 3 and 6 post-treatment 3. PFTs: at months 3, 6 and 12 post-treatment 4. ECG: at months 6 and 12 post-treatment Appropriate investigations and assessments will be performed if the patient becomes symptomatic in between trial follow-up appointments.
Overall study start date	01/01/2009
Overall study end date	01/09/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	10 - 36
Total final enrolment	18
Participant inclusion criteria	Queries about inclusion criteria should be addressed prior to entry into the study. Patients are eligible for the study if all of the following criteria are met: 1. Histologically or cytologically confirmed stage III NSCLC 2. World Health Organization (WHO) performance status 0 or 1 3. Life expectancy greater than 6 months 4. Inoperable disease as assessed by a Lung Cancer Multi-Disciplinary Team (MDT) with input from Thoracic Surgeon; or operable but the patient refuses surgery 5. Aged 18 or over (no upper age limit), either sex 6. No prior thoracic radiotherapy 7. No prior lobectomy/pneumonectomy 8. No prior systemic chemotherapy 9. Willing and able to give informed consent 10. Adequate pulmonary function test (PFT) results: forced expiratory volume in one second (FEV1) and/or carbon monoxide transfer factor (DCLO) greater than or equal to 40% of predicted 11. For women with childbearing potential: 11.1. Negative pregnancy test 11.2. Adequate contraceptive precautions
Participant exclusion criteria	Patients are ineligible for the trial if any of the following criteria are met: 1. Previous or current malignant disease likely to interfere with the protocol treatment or comparisons 2. Medically unstable (e.g. unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcaemia, cardiovascular disease such as congestive cardiac failure) 3. Previous diagnosis of interstitial lung disease 4. Previous diagnosis of spinal cord disease 5. Women of childbearing potential who are not practicing adequate contraceptive precautions 6. Women who are pregnant or lactating 7. Connective tissue disorders (e.g. scleroderma, systemic lupus erythematosus)
Recruitment start date	01/01/2009
Recruitment end date	01/09/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Weston Park Hospital

Sheffield
S10 2SJ
United Kingdom

Sponsor information

Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

Research Department
3rd Floor, Pegasus House
463a Glossop Road
Sheffield
S10 2QD
England
United Kingdom

Email	lance.burn@sth.nhs.uk
Website	http://www.sth.nhs.uk/
"ROR"	https://ror.org/018hjpz25

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK) (ref: C9759/A9766)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/03/2016		Yes	No
Plain English results			02/09/2022	No	Yes

Editorial Notes

02/09/2022: Cancer Research UK plain English results link and total final enrolment added.