Trial registered on ANZCTR


Trial ID
ACTRN12610000479000
Ethics application status
Approved
Date submitted
3/12/2009
Date registered
10/06/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
Hypofractionated image guided radiotherapy ("stereotactic") versus conventional radiotherapy for inoperable early stage I non small cell lung cancer (NSCLC).
Scientific title
Trans Tasman Radiation Oncology Group (TROG) 09.02 - A randomised phase III trial comparing time to local failure between highly conformal hypofractionated image guided ("stereotactic") radiotherapy (HypoRT) versus conventionally fractionated radiotherapy for inoperable early stage I non small cell lung cancer
Secondary ID [1] 1169 0
Clinical Trials.gov Registry ID NCT01014130
Universal Trial Number (UTN)
Trial acronym
CHISEL

Health condition
Health condition(s) or problem(s) studied:
Stage I non small cell lung cancer 252337 0
Condition category
Condition code
Cancer 252526 252526 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Investigational. Treatment: Other - Hypofractionated radiotherapy (HypoRT). Highly conformal hypofractionated radiotherapy to a total dose of 54Gy in 3 fractions, 18 Gy each, delivered weekly on days 0, 7 and 14 with a maximum deviation of +/- 2 days from the specified time allowed.
Intervention code [1] 255647 0
Treatment: Other
Intervention code [2] 255648 0
Treatment: drugs
Comparator / control treatment
Arm 2: Standard of Care. Treatment: other - Conventionally fractionated radiotherapy (ConRT). Standard radiotherapy to a total dose of 60-66Gy delivered in daily 2Gy in 30-33 fractions over 6-6.5 weeks.

Treatment: drugs - Carboplatin. If chemotherapy is the institutional practice for this group of patients, concurrent carboplatin (Area Under the Curve (AUC)=2/wk) will be given weekly with paclitaxel for 6 weeks.

Treatment: drugs - Paclitaxel. If chemotherapy is the institutional practice for this group of patients, concurrent paclitaxel (45mg/m2/wk) will be given intravenously, weekly with carboplatin for 6 weeks..
Control group
Active

Outcomes
Primary outcome [1] 253408 0
Time to Local Failure. Measured from date of randomisation to time of local failure. Local failure will be measured via clinical assessment (physical examination and imaging where indicated) and measurement of local disease using the Response Evaluation Criteria in Solid Tumours (RECIST) criteria
Timepoint [1] 253408 0
At baseline, weekly during radiotherapy treatment, 3 monthly (post radiotherapy) for 2 years, then 6 monthly until 2 years following the end of treatment.
Secondary outcome [1] 262511 0
Overall Survival. Measured from date of randomisation to death from any cause. Clinical assesments and ongoing follow-up.
Timepoint [1] 262511 0
Completion of two year follow-up period for all patients. Patients will be assesed within two weeks of starting radiotherapy, weekly during radiotherapy (or in the case of the experimental arm, on each day of treatment), then at 1 month post radiotherapy, then every 3 months for 2 years and then 6 monthly until two years following the end of treatment of the last patient to be accrued.
Secondary outcome [2] 262512 0
Cancer Specific Survival. Measured from date of randomisation to cancer related death. Any clinical assessment, imaging or other clinically significant assessment used to diagnose cancer related death.
Timepoint [2] 262512 0
Completion of two year follow-up period for all patients. Patients will be assesed within two weeks of starting radiotherapy, weekly during radiotherapy (or in the case of the experimental arm, on each day of treatment), then at 1 month post radiotherapy, then every 3 months for 2 years and then 6 monthly until two years following the end of treatment of the last patient to be accrued.
Secondary outcome [3] 262513 0
Toxicity. Measured using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTC AE) v 4.0.
Timepoint [3] 262513 0
Completion of two year follow-up period for all patients. Patients will be assesed within two weeks of starting radiotherapy, weekly during radiotherapy (or in the case of the experimental arm, on each day of treatment), then at 1 month post radiotherapy, then every 3 months for 2 years and then 6 monthly until two years following the end of treatment of the last patient to be accrued.
Secondary outcome [4] 262514 0
Quality of Life. Measured using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Cancer 30 (EORTC QLQ-C30) and Lung Cancer (LC13).
Timepoint [4] 262514 0
At baseline, last day of radiotherapy, then 3 monthly (post radiotherapy) for 2 years, then 6 monthly until 2 years following the end of treatment.

Eligibility
Key inclusion criteria
Patients may be included in the trial only if they meet all of the following criteria:
· Histologically or cytologically confirmed non-small cell lung cancer diagnosed within 6 weeks prior to randomisation. The following primary cancer types are eligible:
squamous cell carcinoma, adenocarcinoma, large cell carcinoma, bronchioloalveolar
cell carcinoma, large cell neuroendocrine, and non-small cell carcinoma not otherwise
specified.
· Aged 18 years or older
· Disease stage T1N0 or T2aN0 (International Union against Cancer (UICC Tumour, Nodes, Metastases (TNM) stage, 7th Ed, 2009), based on Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) performed within 4 weeks prior to randomisation. T stage should be based on tumour size alone (i.e. no atelectasis).
· An Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
· The tumour has a peripheral location, defined as at least 1 cm beyond the
mediastinum and 2 cm beyond the bifurcation of the lobar bronchi.
Tumour is assessed as inoperable either i) because of unfitness for surgery as
determined by the lung multidisciplinary team including thoracic surgeons and
respiratory physicians or ii) because the patient refuses surgery.
· Female patients of childbearing potential and male patients must agree to use
adequate contraception throughout the treatment phase of the study.
· If female and of childbearing potential, a negative pregnancy test was performed within 7 days prior to randomisation.
· Patient is expected to survive and be available for follow up for two years.
· Patient has provided written informed consent for participation in this trial prior to any protocol-specified procedures.
· Patient undergoing chemoradiation has satisfactory haematological and biochemical
parameters as described below:
Absolute Neutrophil count (ANC) greater than or equal to 1.5 x 109, Platelets greater than or equal to 100 x 109/L, Hemoglobin (Hb) greater than or equal to 100g/L, creatinine clearance greater than or equal to
40mls/min (patients with calculated creatinine clearance greater than or equal to 40mls/min and < 60mls/min must have this confirmed by nuclear medicine Glomerular Filtartion Rate (GFR) scan), bilirubin <1.5 x Upper Limit of Normal (ULN) and Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)< 2x ULN
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who fulfil any of the following criteria are not eligible for admission to the trial:
· Centrally located tumours (< 1.0 cm from mediastinum or < 2.0 cm from bifurcation of
lobar bronchus).
· Tumours within 1.0 cm of the chest wall.
· Prior chemotherapy.
· Previous radiotherapy to the area to be treated.
· Women who are pregnant or lactating.
· Patient with multiple synchronous primary tumours requiring radiotherapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Prior to patient enrolment, the investigator should ensure that all of the following
requirements are met:
· The patient meets all inclusion criteria and none of the exclusion criteria should apply.
· The patient has signed and dated the consent form.
· All pre-randomisation baseline assessments and investigations have been performed.
· The eligibility checklist has been completed, signed and dated.
The following documents should be faxed to the TROG Trial Centre:
· Eligibility checklist
· De-identified consent form
· Histological/cytological report confirming NSCLC
The Trial Coordinator will verify the completeness of the eligibility checklist upon receipt of the document and follow up with the participating centre in the event of a discrepancy.
Participants will be randomised in the ratio of 1:1 using the minimisation technique.
This is not a blinded study, treatment allocation is known.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be stratified by T stage (T1 or T2a) and whether medically operable or inoperable. Randomisation will be by the minimisation technique.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy

Recruitment
Anticipated date of first participant enrolment
31/12/2009
Actual date of first participant enrolment
31/12/2009
Anticipated date last participant enrolled
30/06/2015
Actual date last participant enrolled
22/06/2015
Target sample size
100
Actual sample size
101
Recruitment status
Closed: follow-up continuing
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 1685 0
The Canberra Hospital - Garran
Recruitment hospital [2] 1686 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 1687 0
Prince of Wales Hospital - Randwick
Recruitment hospital [4] 1688 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [5] 1689 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 1690 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 1693 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [8] 1694 0
The Alfred - Prahran
Recruitment hospital [9] 1695 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [10] 1697 0
Peter MacCallum Cancer Centre, Moorabbin
Recruitment hospital [11] 3856 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [12] 3857 0
Royal Hobart Hospital - Hobart
Recruitment hospital [13] 4180 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [14] 4181 0
Bendigo Health Care Group - Bendigo Hospital - Bendigo
Recruitment hospital [15] 4182 0
Epworth Eastern Hospital - Box Hill
Recruitment outside Australia
Country [1] 6923 0
New Zealand
State/province [1] 6923 0
Auckland
Country [2] 6924 0
New Zealand
State/province [2] 6924 0
Christchurch
Country [3] 6925 0
New Zealand
State/province [3] 6925 0
Palmerston North

Funding & Sponsors
Funding source category [1] 256126 0
Government body
Name [1] 256126 0
Cancer Australia
Address [1] 256126 0
PO BOX 1201
Dickson ACT 2602
Country [1] 256126 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group (TROG)
Address
TROG Central Office
PO Box 88
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 251468 0
Individual
Name [1] 251468 0
Professor David Ball
Address [1] 251468 0
Peter MacCallum Cancer Centre
1 St Andrews Place
East Melbourne, Victoria, 3002
Country [1] 251468 0
Australia
Other collaborator category [1] 277701 0
Other Collaborative groups
Name [1] 277701 0
Australasian Lung cancer Trials Group (ALTG)
Address [1] 277701 0
44 Brookes Street
Bowen Hills, QLD 4006
Australia
Country [1] 277701 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258217 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [1] 258217 0
Ethics Committee Secretariat
Peter MacCallum Cancer Centre
Locked Bag 1, A Beckett St
East Melbourne
Victoria 8006
Ethics committee country [1] 258217 0
Australia
Date submitted for ethics approval [1] 258217 0
Approval date [1] 258217 0
14/09/2009
Ethics approval number [1] 258217 0
09/42

Summary
Brief summary
The purpose of this study is to investigate whether radiotherapy given as three large doses over a period of two weeks (hypofractionated radiotherapy) is more effective than standard radiotherapy for patients with non-small cell lung cancer that has not spread beyond the lung. Who is it for? You may be eligible to join this study if you aged 18 years or above and have a confirmed diagnosis of non-small cell lung cancer within 6 weeks of study enrolment. Study details Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will receive the current standard of care treatment, which consists of chemotherapy and radiotherapy given in a number of small doses over a period of about 6 weeks. Participants in the other group will instead receive hypofractionated radiotherapy (HypoRT) in three large doses over a period of 2 weeks. All participants will be regularly monitored for up to 2 years in order to evaluate treatment response, survival, toxicity and quality of life. This will help us to determine whether hypofractionated radiotherapy is more effective, results in longer life expectancy and if it is just as safe as standard fractionated radiotherapy.
Trial website
www.trog.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30577 0
Dr David Ball
Address 30577 0
Peter MacCallum Cancer Centre
Locked Bag 1, A’Beckett Street
East Melbourne VIC 8006
Country 30577 0
Australia
Phone 30577 0
+61 3 9656 1648
Fax 30577 0
Email 30577 0
david.ball@petermac.org
Contact person for public queries
Name 13824 0
Ms Marijana Vanevski
Address 13824 0
BaCT Peter MacCallum Cancer Centre 1 St Andrews Place East Melbourne, Victoria, 3002
Country 13824 0
Australia
Phone 13824 0
+61 3 9656 1266
Fax 13824 0
+61 3 9656 1420
Email 13824 0
Marijana.Vanevski@petermac.org
Contact person for scientific queries
Name 4752 0
Ms Marijana Vanevski
Address 4752 0
BaCT
Peter MacCallum Cancer Centre
1 St Andrews Place
East Melbourne, Victoria, 3002
Country 4752 0
Australia
Phone 4752 0
+61 3 9656 1266
Fax 4752 0
+61 3 9656 1420
Email 4752 0
Marijana.Vanevski@petermac.org