Phase I study of Continuous Hyperfractionated Accelerated RadioTherapy - Escalated Dose

ISRCTN ISRCTN45918260
DOI https://doi.org/10.1186/ISRCTN45918260
Protocol serial number CHART-ED Version Final 2.0
Sponsor Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Funder Cancer Research UK (CRUK) (UK) (ref: C9759/A9766)
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 of protocol

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

matthew.hatton@sth.nhs.uk

Study information

Primary study designInterventional
Study designMulticentre phase I feasibility study
Secondary study designNon randomised study
Study type Participant information sheet
Scientific titleA dose escalation phase I study of continuous, hyperfractionated, accelerated radiotherapy (CHART) in patients with inoperable non-small cell lung cancer
Study acronymCHART-ED
Study objectivesThe 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)
Health condition(s) or problem(s) studiedNon-small cell lung cancer (NSCLC)
InterventionPre-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 typeOther
Primary outcome measure(s)

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

Key secondary outcome measure(s)

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.

Completion date01/09/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration36
Total final enrolment18
Key inclusion criteriaQueries 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
Key exclusion criteriaPatients 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)
Date of first enrolment01/01/2009
Date of final enrolment01/09/2011

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summary
IPD sharing planNot 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
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
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.

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