Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001198910
Ethics application status
Approved
Date submitted
14/09/2020
Date registered
10/11/2020
Date last updated
2/11/2021
Date data sharing statement initially provided
10/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Moderately Hypofractionated Chemoradiation and Immunotherapy for Unresectable Locally Advanced Non-Small Cell Lung Cancer (MODERN-LUNG)
Scientific title
Phase 2 Study of a Moderately Hypofractionated Schedule of Chemoradiation followed by Immunotherapy for Unresectable Locally Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 302299 0
CMNDRO-2005
Universal Trial Number (UTN)
Trial acronym
MODERN-LUNG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
lung cancer 319050 0
Condition category
Condition code
Cancer 317004 317004 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive radiotherapy with chemotherapy followed by maintenance immunotherapy.
Radiotherapy will be delivered to a total dose of 55 Gray (Gy) in 20 fractions at 2.75 Gy per fraction daily, 5 days per week over 4 weeks.
Chemotherapy will be delivered intravenously weekly for 4 weeks consisting of Paclitaxel (45mg/m2) and carboplatin (2AUC). Other platinum doublets allowable at the discretion of medical oncologists after discussion with Principal Investigator.
Maintenance immunotherapy consists of Durvalumab (10mg/kg) given in 14 day cycles to a maximum of 26 cycles or until disease progression or unacceptable toxicity.
Treatment details will be captured within the electronic case record forms.
Intervention code [1] 318587 0
Treatment: Other
Intervention code [2] 318588 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325113 0
Safety as assessed by CTCAE grading v5.0, specifically pneumonitis and oesophagitis
Timepoint [1] 325113 0
Weekly during chemoradiotherapy (CRT), 6 weeks post CRT, 3 monthly until 2 years post CRT and then 6 monthly until study closure. All participants will be followed to a minimum of 12 months after CRT ceasing when the final participant reaches 12 months post CRT.
Secondary outcome [1] 386890 0
Feasibility as assessed by rate of treatment completion and compliance.
Treatment details including drugs administered, dates given and doses will be collected by direct entry into the study database at Calvary Mater Newcastle. Any changes to planned treatment including omissions, dose reductions or delays will also be captured.
Timepoint [1] 386890 0
End of treatment
Secondary outcome [2] 386891 0
Efficacy of treatment as assessed by rates of progression free survival, overall survival and recurrence pattern.
Disease status data will be collected via routine participant check-ups with their clinician.
Timepoint [2] 386891 0
3 monthly until 2 years post CRT then 6 monthly thereafter until the final participant reaches the 12 month post CRT timepoint..
Secondary outcome [3] 386892 0
Late toxicities as assessed by CTCAE grading v5.0
Timepoint [3] 386892 0
3 monthly until 2 years post CRT then 6 monthly thereafter until the final participant reaches the 12 month post CRT timepoint..

Eligibility
Key inclusion criteria
Unresectable locally advanced Non-small cell lung carcinoma
Considered suitable to receive chemoradiation and immunotherapy
ECOG performance status 0-2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to meet radiotherapy planning constraints
Previous thoracic radiotherapy
Life expectancy less than 3 years
Received induction chemotherapy prior to chemoradiotherapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
The stopping rules for this study are developed using a Bayesian approach. There are two parameters corresponding to the two primary endpoints that are being estimated:
The proportion of patients experiencing:
• Grade >/= 3 pneumonitis
• Grade >/= 3 oesophagitis

The number of events for each of these outcomes is assumed to follow a Binomial distribution, and the prior distribution for these parameters is assumed to follow a conjugate Beta distribution, with shape parameters = 1, and 5. This corresponds to a prior mean of 1/ (1+5) = 16.67% for both parameters. A uniform prior was considered however this was deemed overly aggressive at stopping the study early, we have adopted for a less aggressive prior considering the risk of adverse events is reasonably low (this treatment protocol is used clinically). The corresponding posterior distributions follow Beta distribution, from which the posterior probability that the risk exceeds the following thresholds is obtained on each adverse event occurrence:
• = 10% Grade >/= 3 pneumonitis
• = 20% Grade >/= 3 oesophagitis

The study will be stopped if either of these posterior probabilities exceeds 99%. Then the 4 week schedule would not be pursued further in a phase 3 trial. The trial committee will be reviewing every Grade >/= 3 toxicities in real time and will be monitoring outcomes every three months or sooner if required.

A sample size of 50 patients was chosen since the probability that at least one adverse event for either outcome occurring was greater than 95%. The operating characteristics of the decision rule where investigated through simulation (n=10000 simulated trials). When the true risk parameters were set to 0.1 and 0.2 respectively, the proportion of trials that were incorrectly stopped early was 7.5%. When the true risk parameters were set to 0.2 and 0.3 respectively, the proportion of `trials that were correctly stopped early was 80%.

• Progression-free survival will be measured from D1 CRT to the time of first progression.
• Overall survival will be calculated as the difference between D1 CRT and the date of death or the date of last follow-up.
• Survival will be estimated using the Kaplan-Meier method. For all other data, descriptive statistics will be used.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
16/11/2020
Actual
15/04/2021
Date of last participant enrolment
Anticipated
2/11/2022
Actual
Date of last data collection
Anticipated
2/11/2023
Actual
Sample size
Target
50
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 17522 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 17523 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 21006 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [4] 21007 0
Blacktown Hospital - Blacktown
Recruitment hospital [5] 21008 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 31252 0
2298 - Waratah
Recruitment postcode(s) [2] 31253 0
2170 - Liverpool
Recruitment postcode(s) [3] 35839 0
2560 - Campbelltown
Recruitment postcode(s) [4] 35840 0
2148 - Blacktown
Recruitment postcode(s) [5] 35841 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 306725 0
Hospital
Name [1] 306725 0
Calvary Mater Newcastle
Country [1] 306725 0
Australia
Primary sponsor type
Hospital
Name
Calvary Mater Newcastle
Address
Corner Edith & Platt Streets
Waratah, Newcastle
New South Wales 2298
Country
Australia
Secondary sponsor category [1] 307273 0
None
Name [1] 307273 0
Address [1] 307273 0
Country [1] 307273 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306894 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 306894 0
Ethics committee country [1] 306894 0
Australia
Date submitted for ethics approval [1] 306894 0
05/08/2020
Approval date [1] 306894 0
02/09/2020
Ethics approval number [1] 306894 0
2020/ETH02030

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105378 0
Dr Joanna JANE Ludbrook
Address 105378 0
Radiation Oncology, Calvary Mater Newcastle, Locked Bag 7 HRMC NSW 2310
Country 105378 0
Australia
Phone 105378 0
+61 2 4014 3633
Fax 105378 0
Email 105378 0
[email protected]
Contact person for public queries
Name 105379 0
Sarah Gallagher
Address 105379 0
Radiation Oncology, Calvary Mater Newcastle, Locked Bag 7 HRMC NSW 2310
Country 105379 0
Australia
Phone 105379 0
+61 2 4014 3949
Fax 105379 0
Email 105379 0
[email protected]
Contact person for scientific queries
Name 105380 0
Joanna JANE Ludbrook
Address 105380 0
Radiation Oncology, Calvary Mater Newcastle, Locked Bag 7 HRMC NSW 2310
Country 105380 0
Australia
Phone 105380 0
+61 2 4014 3633
Fax 105380 0
Email 105380 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.