Condition category
Cancer
Date applied
10/12/2008
Date assigned
03/12/2009
Last edited
16/05/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Matthew Hatton

ORCID ID

Contact details

Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
matthew.hatton@sth.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CHART-ED Version Final 2.0

Study information

Scientific title

A dose escalation phase I study of continuous, hyperfractionated, accelerated radiotherapy (CHART) in patients with inoperable non-small cell lung cancer

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

Oxfordshire Research Ethics Committee (REC) A on 21/10/2008 (ref: 08/H0604/147)

Study design

Multicentre phase I feasibility study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

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

Phase

Phase I

Drug names

Primary outcome measures

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 trial start date

01/01/2009

Overall trial end date

01/09/2011

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

10 - 36

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

United Kingdom

Trial participating centre

Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom

Sponsor information

Organisation

Sheffield Teaching Hospitals NHS Foundation Trust (UK)

Sponsor details

Research Department
3rd Floor
Pegasus House
463a Glossop Road
Sheffield
S10 2QD
United Kingdom
lance.burn@sth.nhs.uk

Sponsor type

Government

Website

http://www.sth.nhs.uk/

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (ref: C9759/A9766)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in:
Continuous Hyperfractionated Accelerated RadioTherapy – Escalated Dose (CHART-ED): A Phase I study.
Hatton M, Hill R, Wilson P, Atherton P, Morgan S, Dickson J, Murray K, Paul J.
Radiotherapy and Oncology 111 suppl 1 S231; 2014

Publication citations

Additional files

Editorial Notes