Trial registered on ANZCTR


Trial ID
ACTRN12612001211853
Ethics application status
Approved
Date submitted
2/11/2012
Date registered
15/11/2012
Date last updated
17/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 11.03 A Randomised Phase III Trial of High Dose Palliative Radiotherapy (HDPRT) Versus Concurrent Chemotherapy + HDPRT (C-HDPRT) in Patients with Good Performance Status, Locally Advanced/Small Volume Metastatic Non Small Cell Lung Cancer (NSCLC) Not Suitable for Radical Chemo-Radiotherapy (P_LUNG GP)
Scientific title
TROG 11.03 A Randomised Phase III Trial of High Dose Palliative Radiotherapy (HDPRT) Versus Concurrent Chemotherapy + HDPRT (C-HDPRT) in Patients with Good Performance Status, Locally Advanced/Small Volume Metastatic Non Small Cell Lung Cancer (NSCLC) Not Suitable for Radical Chemo-Radiotherapy (P_LUNG GP)
Secondary ID [1] 281485 0
Nil
Universal Trial Number (UTN)
Trial acronym
P_LUNG GP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer (NSCLC) 287748 0
Condition category
Condition code
Cancer 288089 288089 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Chemotherapy + High Dose palliative Radiation Therapy (C-HDPRT)
1. Radiation Therapy; 40Gy/20f (2Gy/f, 4-5f/week)
2. Chemotherapy; IV cisplatin 20mg/m2 (days 1, 8, 15, 22 of RT) plus IV vinorelbine 25mg/m2 (days 1, 8 and 22 of RT).
Intervention code [1] 285992 0
Treatment: Other
Intervention code [2] 285993 0
Treatment: drugs
Comparator / control treatment
High Dose palliative Radiation Therapy (HDPRT) alone

1. Radiation Therapy; 36Gy/12f (3Gy/f, 4-5f/week)
Control group
Active

Outcomes
Primary outcome [1] 288296 0
The primary outcome of this trial is to compare high dose palliative radiotherapy (HDPRT) versus concurrent chemotherapy and HDPRT (C-HDPRT), with respect to the relief of dyspnoea, cough, haemoptysis and chest pain as assessed by change in total symptom burden from baseline to six weeks after the completion of treatment, and the response for each component symptom separately (dyspnoea, cough, haemoptysis, chest pain)
Timepoint [1] 288296 0
Toxicity assesments (NCIC CTCAE v 3.0) and physical exams performed at pre registration, pre treatemnt, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment.
Secondary outcome [1] 299777 0
Comparison of the two regimens in terms of dysphagia during treatment by clinical examination and patient reported outcomes.
Timepoint [1] 299777 0
Pre registration, pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.
Secondary outcome [2] 299869 0
Comparison of the two regimens in terms of thoracic symptom response rate by clinical examination and patient reported outcomes
Timepoint [2] 299869 0
Pre registration, pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.
Secondary outcome [3] 299870 0
Comparison of the two regimens in terms of duration of thoracic symptom response by clinical examination and patient reported outcomes.
Timepoint [3] 299870 0
Pre registration, pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.
Secondary outcome [4] 299871 0
Comparison of the two regimens in terms of Quality of Life (QOL) Questionniares (QLQ-C30, QLQ-LC13) and Physician rated Spitzer index
Timepoint [4] 299871 0
Pre registration, pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.
Secondary outcome [5] 299872 0
Comparison of the two regimens in terms of Toxicity (NCIC CTCAE v 3.0)
Timepoint [5] 299872 0
Toxicity assesments (NCIC CTCAE v 3.0) at Pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.
Secondary outcome [6] 299873 0
Comparison of the two regimens in terms of Progression-free survival by physical exams and imaging.
Timepoint [6] 299873 0
Physical Examinations; pre registration, pre treatment, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.

Medical Imaging (CT scans +/-PET); Pre regisatration, 6 weeks post treatment, 3 months post treatment and then 3 monthly until progression (if clinically indicated).
Secondary outcome [7] 299874 0
Overall survival (clincal assessments)
Timepoint [7] 299874 0
Pre treatemnt, during treatment, end of treatment, 2 wks post treatment, 6 weeks post treatment, 3 months post treatment, 6 months post treatment and then 3 monthly until progression.

Eligibility
Key inclusion criteria
1. Aged 18 years or older
2. ECOG PS 0-1,
3. Histological or cytological proven stage III or IV NSCLC of any subtype: Adenocarcinoma, Squamous Cell Carcinoma (SCC), NSCLC Not Otherwise Specified (NOS) or Other (including Large Cell Undifferentiated).
4. Symptoms due to intrathoracic disease (at least one of cough, dyspnoea, haemoptysis, chest pain),
5. Patients with Stage III NSCLC not suitable for radical chemo-radiotherapy (due to concurrent medical illness, weight loss > 10% or tumour volume too large for radical radiation fields (e.g. dose constraints for organs at risk cannot be met using radical radiation fields or at the discretion of the investigator) or patients with locally advanced thoracic disease and a FDG-PET detected solitary metastasis (small volume Stage IV disease), Not cerebral metastasis
6. Planned for HDPRT to achieve local control
7. Adequate organ function;
a) Bone marrow: Haemoglobin (Hb) >/= 100g/l, Absolute neutrophil count (ANC) >/= 1.5 , Platelet count >/= 100
b) Hepatic: Serum bilirubin </= 1.0 x upper limit of normal (ULN), AST/ALT </= 2.0 x ULN, ALP </= 2.5 x ULN.

c) Renal: Creatinine Clearance >/= 55 ml/min
8. No prior therapy for NSCLC
9. Able to commence Radiotherapy no later than 6 weeks, but preferably within 4 weeks from the time of participant randomisation. It is preferred that RT be commenced on a Monday or Tuesday.
10. Has provided written informed consent to participate in this trial
11. Participants capable of childbearing are using adequate contraception
12. Available for follow-up for a minimum of 3 months.
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Receiving treatment with another investigational agent
2. History of any other cancer (except non-melanomatous skin cancer or carcinoma in situ of the cervix) unless in complete remission and off all therapy for that cancer for at least 3 years.
3. Women who are pregnant or lactating
4. Previous radiotherapy to the area to be treated, at any time.
5. Significant medical conditions which in the opinion of the investigator would compromise the planned delivery of the chemotherapy and radiotherapy or which may be potentially exacerbated by these modalities

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)
Patients will be randomised in the ratio of 1:1 between the two arms, HDPRT and C-HDPRT. Allocation is determined by central randomisation by computer and allocation concealment is used.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Allocation to treatment arms will be stratified by tumour stage (III, IV), tumour histology (adenocarcinoma, SCC, other), major chest symptoms (presence or absence of each of dyspnoea, cough, haemoptysis and chest pain) and treating Institution, using the minimisation technique (with a random component).
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
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Actual
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,VIC
Recruitment hospital [1] 2776 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 2777 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 2778 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [4] 2779 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 2780 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 2781 0
The Townsville Hospital - Douglas
Recruitment hospital [7] 2782 0
Peter MacCallum Cancer Institute - East Melbourne
Recruitment hospital [8] 3474 0
Gosford Hospital - Gosford
Recruitment hospital [9] 3477 0
St Andrew's Toowoomba Hospital - Toowoomba
Recruitment hospital [10] 3478 0
Cairns Base Hospital - Cairns
Recruitment hospital [11] 3479 0
Gold Coast Hospital - Southport
Recruitment hospital [12] 4109 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [13] 4187 0
Epworth Eastern Hospital - Box Hill

Funding & Sponsors
Funding source category [1] 286258 0
Government body
Name [1] 286258 0
Cancer Australia
Address [1] 286258 0
Locked Bag 3
Strawberry Hills
NSW, 2012
Country [1] 286258 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group
Address
TROG Central Office
PO Box 88
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 285058 0
None
Name [1] 285058 0
Address [1] 285058 0
Country [1] 285058 0
Other collaborator category [1] 277151 0
Other Collaborative groups
Name [1] 277151 0
Australasian Lung Trials Group
Address [1] 277151 0
ALTG Group Manager
The Australian Lung Foundation
44 Brookes Street
Bowen Hills, QLD 4006
Country [1] 277151 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288335 0
Metro South Hospital and Health Service Human Research Ethics Committee (EC00167)
Ethics committee address [1] 288335 0
Ipswich Road
Woolloongabba
Qld 4102
Ethics committee country [1] 288335 0
Australia
Date submitted for ethics approval [1] 288335 0
01/05/2012
Approval date [1] 288335 0
28/06/2012
Ethics approval number [1] 288335 0
HREC/12/QPAH/172

Summary
Brief summary
Lung cancer is the fifth most common cancer in Australia and the leading cause of cancer deaths. The majority of lung cancers are of the Non Small Cell Lung Cancer (NSCLC) histological type and most patients present with inoperable Stage III or IV disease.

The population to be studied in this trial are patients with inoperable NSCLC who have a good PS but locally advanced or limited metastatic disease for whom radical CT-RT (=60Gy) is not feasible either due to tumour extent or patient factors. In these patients, the aim of therapy is to achieve symptom control and maintain Quality of Life (QOL). However, the optimal treatment regimen for this group is uncertain.

Hypothesis-
The hypothesis is that the addition of chemotherapy to high dose palliative radiotherapy in these patients will maximises intrathoracic symptom palliation (both the extent of improvement and its duration), which will lead to an improvement in QOL, and is associated with acceptable toxicity, compared with high dose palliative radiotherapy alone.

Objectives-
The Primary objective is to compare, in this group of patients, high dose palliative radiotherapy (HDPRT) versus concurrent chemotherapy and HDPRT (C-HDPRT), with respect to
- The relief of dyspnoea, cough, haemoptysis and chest pain as assessed by change in total symptom burden from baseline to six weeks after the completion of treatment.
- Response for each component symptom separately (dyspnoea, cough, haemoptysis, chest pain)

The secondary objectives are to compare the two regimens in terms of; Dysphagia during treatment, Thoracic symptom response rate, Duration of thoracic symptom response , QOL, Toxicity, Progression-free survival and Overall survival.

The exploratory/tertiary objectives are;
- to determine how much improvement in QoL and symptom palliation would be necessary to make the inconvenience due to the longer duration of radiotherapy of C-HDPRT worthwhile, relative to HDPRT. This objective will be addressed in the Patient Preferences Substudy.
- Analyse serum protein glycosylation changes and exosomes to identify potential biomarkers of disease response and progression
- Prospectively collect and bank tumour tissue and blood samples from this cohort of patients for future evaluation of potential biological markers

End Points-
Primary -
- Change from baseline at 6 weeks after treatment in the Intrathoracic Symptom Burden Index
- Change from baseline at 6 weeks after treatment in each of the component symptoms, dyspnoea, cough, haemoptysis and chest pain.
Secondary -
- Profile of change from baseline of Intrathoracic Symptom Burden Index, and of component symptoms, by time (6 weeks, 3, 6, 12, 24 months)
- Thoracic symptom response rate and response duration
- Physician’s rating of cough, dyspnoea, haemoptysis and chest pain, summed into a symptom index and performance status (Karnofsky) and QOL (Spitzer)
- Toxicity measured by NCIC CAE v 3.0
- Tumour response, Progression-free survival and Overall survival

Trial Design-
This is a multi-centre, two-arm, randomised (1:1) Phase III trial to compare high dose palliative radiotherapy (HDPRT) versus concurrent chemotherapy and HDPRT (C-HDPRT) in patients with inoperable NSCLC.

1) ARM A (control arm): High dose palliative RT (HDPRT) alone (36Gy/12 fractions, 4-5 fractions/week) or

2) ARM B (investigational arm): Chemotherapy + HDPRT (40Gy/20fractions, 4-5 fractions/week + IV cisplatin 20mg/m2 days 1, 8, 15, 22 + IV vinorelbine 25mg/m2 days1, 8, 22). (C + HDPRT)

All eligible patients will be stratified according to tumour stage, histology, major chest symptoms and treating institution.

The total participant accrual for this trial will be 130. The accrual period is expected to be 41 months and total study duration 55 months.
Trial website
www.trog.com.au (http://www.trog.com.au/Default.aspx?tabid=71)
Trial related presentations / publications
Oral presentation - P-LUNG trial update TROG 2016 ASM by A/Prof margot Lehman
Public notes

Contacts
Principal investigator
Name 34907 0
Dr Margot Lehman
Address 34907 0
Princess Alexandra Hospital Ipswich Road Woolloongabba Qld 4102
Country 34907 0
Australia
Phone 34907 0
+61 (0)7 31762111
Fax 34907 0
Email 34907 0
Margot.Lehman@health.qld.gov.au
Contact person for public queries
Name 18154 0
Ms Cassie Freriechs
Address 18154 0
Delivery Point 10, Ground Floor
Princess Alexandra Hospital
Ipswich Road
Woolloongabba Qld 4102
Country 18154 0
Australia
Phone 18154 0
+61 7 3176 8292
Fax 18154 0
+61 (0)7 31761929
Email 18154 0
Cassie.Freriechs@health.qld.gov.au
Contact person for scientific queries
Name 9082 0
Dr Margot Lehman
Address 9082 0
Radiation Oncology
Princess Alexandra Hospital
Ipswich Road
Woolloongabba Qld 4102
Country 9082 0
Australia
Phone 9082 0
+61 (0)7 31762111
Fax 9082 0
+61 (0)7 31761929
Email 9082 0
Margot.Lehman@health.qld.gov.au