A phase I/II trial of isotoxic accelerated radiotherapy in the treatment of patients with non-small cell lung cancer

ISRCTN	ISRCTN74841904
DOI	https://doi.org/10.1186/ISRCTN74841904
EudraCT/CTIS number	2010-020075-23
ClinicalTrials.gov number	NCT01537991
Secondary identifying numbers	9703

Submission date: 10/06/2011
Registration date: 10/06/2011
Last edited: 04/09/2019

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-trial-looking-at-higher-dose-radiotherapy-for-non-small-cell-lung-cancer-i-start

Study website

Contact information

Dr Lisette Nixon
Scientific

6th Floor
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom

Phone	+44 (0)29 20687458, ext. 87458
Email	nixonls@cardiff.ac.uk

Study information

Study design	Non-randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
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 phase I/II trial of isotoxic accelerated radiotherapy in the treatment of patients with non-small cell lung cancer
Study acronym	I-START
Study hypothesis	The I-START trial is designed to determine the highest doses of radiotherapy that can safely be used in locally advanced non-small cell lung cancer (NSCLC). Patients with NSCLC who are expected to live longer than three months and are fit to receive radical radiotherapy (radiotherapy given with curative intent) will be eligible to participate. All trial participants will receive 20 doses (called fractions) of radiotherapy. Phase I will establish the maximum tolerated dose (MTD) that may be safely delivered to the oesophagus in patients where the oesophagus lies within the radiotherapy high dose region. This will establish the maximum dose to the oesophagus for phase II. Phase II will establish whether this novel radiotherapy regimen is tolerable, safe and sufficiently active in eligible patients to justify its inclusion as an experimental arm in future randomised phase III trials.
Ethics approval(s)	First MREC, 15/09/2010, ref: 10/MRE09/n29
Condition	Topic: National Cancer Research Network; Subtopic: Lung Cancer; Disease: Lung (non-small cell)
Intervention	Phase I will have two groups, each with 6 to 12 particpantss who will be treated at each of up to 4 dose levels until the MTD recommended Phase II dose is identified. 49 patients need to be recruited into Phase II, or which 39 should be toxicity-free at three months for evidence to proceed (base on a Flemming 1 stage design) Radiotherapy, between 58Gy and 65Gy delivered in 20 fractions; Follow Up Length: 24 month(s); Study Entry : Registration only
Intervention type	Other
Primary outcome measure	Grade 3 or 4 toxicities; Timepoint(s): occuring up to three months after radiotherapy
Secondary outcome measures	1. Dose Limiting Toxicity; Timepoint(s): occuring up to six months after radiotherapy (RT) 2. Estabilsh Maximum Tolerated Dose to the oesophagus; Timepoint(s): acute grade 3 or 4 toxicity occuring up to two months after radiotherapy 3. Local control; Timepoint(s): to the date of first clinical evidence of progressive disease at the primary site, or death 4. Overall Survival; Timepoint(s): date of entry to date of death 5. Tumour response; Timepoint(s): assessed using Response Evaluation Criteria In Solid Tumors (RECIST) at 2 months post RT
Overall study start date	01/03/2011
Overall study end date	30/04/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned Sample Size: 121; UK Sample Size: 121. Final: 81.
Participant inclusion criteria	1. Histologically or cytologically confirmed stage II IIIb NSCLC (Appendix II) 2. Inoperable disease (as assessed by a lung cancer MDT with thoracic surgical input) or operable but the patient refuses surgery 3. Disease which can be encompassed within a radical radiotherapy treatment plan in keeping with standard practice at the participating centre 4. World Health Organisation (WHO) Performance Status 0 or 1 (Appendix III) 5. Adequate respiratory function: Forced expiratory volume in the first second (FEV1) = 1.0 litre, diffusing capacity of the lung for carbon monoxide (DLCO) (transfer factor) = 40% of predicted and carbon monoxide transfer coefficient (Kco) (Dlco/VA) > 40% predicted on baseline lung function tests 6. Blood haemoglobin should be = 10g/dL 7. No prior thoracic radiotherapy 8. Age more than or equal to 16 years 9. Considered fit to receive trial treatment 10. Estimated life expectancy of more than 3 months 11. Written informed consent obtained 12. Patient consents for electronic CT scan and planning data to be used for future research 13. Patient is available for follow up; Target Gender: Male & Female ; Lower Age Limit 16 years
Participant exclusion criteria	1. Medically unstable (e.g. unstable diabetes, uncontrolled hypertension, infection, hypercalcaemia or very symptomatic ischaemic heart disease) 2. Previous or current malignant disease likely to interfere with protocol treatment 3. Pancoast tumours 4. Connective tissue disorders (e.scleroderma, systemic lupus erythematosus) 5. Interstitial lung disease 6. Women who are pregnant or lactating 7. Women of childbearing potential who are not using adequate contraceptive precautions
Recruitment start date	12/03/2012
Recruitment end date	10/04/2014

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Cardiff University Centre for Trials Research

College of Biomedical & Life Sciences
Cardiff University
6th Floor, Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom

Sponsor information

Velindre NHS Trust (UK)
Hospital/treatment centre

Velindre Hospital
Velindre Road
Cardiff
CF14 2TL
Wales
United Kingdom

"ROR"	https://ror.org/05ntqkc30

Funders

Funder type

Charity

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): 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

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results	results presented at ASCO	20/05/2018	11/01/2019	No	No

Editorial Notes

04/09/2019: ClinicalTrials.gov number added.
11/01/2019: The following changes have been made:
1. Publication reference added.
2. The trial website has been added.
3. The Cancer Research UK plain English summary link has been updated.
4. The recruitment start date has been changed from 01/03/2011 to 12/03/2012.
5. The recruitment end date has been changed from 01/09/2012 to 10/04/2014.
6. The overall trial end date has been changed from 01/09/2012 to 30/04/2016.
7. The final enrolment number has been added.
12/12/2017: No publications found in PubMed, verifying study status with principal investigator.