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Trial registered on ANZCTR


Registration number
ACTRN12621000586819p
Ethics application status
Submitted, not yet approved
Date submitted
11/02/2021
Date registered
18/05/2021
Date last updated
18/05/2021
Date data sharing statement initially provided
18/05/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
TROG 20.01 CHEST RT: Chemotherapy and Immunotherapy in extensive stage small cell lung cancer with thoracic radiotherapy
Scientific title
A phase II study of platinum and etoposide chemotherapy, durvalumab with thoracic radiotherapy in the first line treatment of patients with extensive-stage small-cell lung cancer
Secondary ID [1] 303170 0
TROG 20.01 CHEST RT
Universal Trial Number (UTN)
U1111-1257-9038
Trial acronym
TROG 20.01 CHEST RT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 320298 0
Extensive Stage Small Cell Lung Cancer 320299 0
Lung Cancer 320300 0
Condition category
Condition code
Cancer 318222 318222 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Durvalumab:
Dose - 1500mg | To be administered by intravenous infusion with chemotherapy every 3 weeks for 4 cycles. Once the chemotherapy cycles complete, 1500mg of Durvalumab will be given every 4 weeks until disease progression (also known as maintenance therapy).

Etoposide:
Dose – as standard practice | Treatment with chemotherapy will be limited to 4 cycles on a 3 weekly schedule. It is to be prescribed and administered by intravenous infusion according to local prescribing information.

Platinum based chemotherapy (Cisplatin or Carboplatin):
Dose – as standard practice | Treatment with chemotherapy will be limited to 4 cycles on a 3 weekly schedule. It is to be prescribed and administered by intravenous infusion according to local prescribing information.

Radiation Therapy:
Dose - 30Gy in 10 fractions | Radiation therapy (RT) to be given either concurrently with cycle 3 or 4 of chemotherapy (called concurrent radiotherapy*) or within 6 weeks of finishing chemotherapy (called consolidation radiotherapy*). Fractions are expected to be delivered daily. All RT treatment should be completed within 15 days
*Note: When RT is to start depends on the location and size of the area to be treated.
Intervention code [1] 319473 0
Treatment: Drugs
Intervention code [2] 319589 0
Treatment: Other
Comparator / control treatment
Single arm open label prospective multicentre Phase II trial
No control group


Control group
Uncontrolled

Outcomes
Primary outcome [1] 326203 0
Safety assessed according to the Common Terminology Criteria for Adverse Events (CTCAE5) for oesophageal or pneumonitis toxicity
Timepoint [1] 326203 0
Adverse events will be recorded via CTCAE v5 at each study visit (i.e chemo-immunotherapy cycle 1, 2 ,3 and 4, then assessments post chemo-immunotherapy at 4 weeks, 8 weeks, 24 weeks, 36 weeks, 52week, 68 weeks, 88 weeks, 104 weeks, 124 weeks, 140weeks and 156 weeks)
Primary outcome [2] 326893 0
Feasibility assessed by the continuation of systematic therapy secondary to radiation toxicities (as assessed by a clinical assessment by a clinician) and the ability of the disease to be encompassed within a reasonable radiation portal and completing the full course of radiation therapy.
Timepoint [2] 326893 0
Clinical assessments of physical examinations, vital signs and adverse event reporting (as power CTCAE5) at 4 weeks, 8 weeks, 24 weeks, 36 weeks, 52week, 68 weeks, 88 weeks, 104 weeks, 124 weeks, 140weeks and 156 weeks post completion of chemo-immunotherapy.
Secondary outcome [1] 390504 0
Overall survival assessed at follow up visits or via medical records of death
Timepoint [1] 390504 0
Death due to any cause as time to event and proportion at one year and 2 years post intervention commencement
Secondary outcome [2] 390505 0
Progression free survival assessed at follow up visits or via medical records
Timepoint [2] 390505 0
Death or disease progression as time to event and proportion at 6 months and 1 year post-intervention commencement
Secondary outcome [3] 390506 0
Patterns of failure assessed by the proportion of patients with first site of failure in: Thoracic, Extra-thoracic or cranial sites, seen on imaging (CT/MRI) and assessed by iRECIST and/or RANO-BM criteria.
(The first site of treatment relapse will be collected and categorised as thoracic, extra-thoracic or cranial).
Timepoint [3] 390506 0
Patterns of failure detected at imaging at cycle 2 / Day 11 of chemo-immunotherapy then at 4 weeks, 8 weeks, 24 weeks, 36 weeks, 52week, 68 weeks, 88 weeks, 104 weeks, 124 weeks, 140weeks and 156 weeks post completion of chemo-immunotherapy.

Eligibility
Key inclusion criteria
- Age greater than or equal to 18,
- Untreated ES-SCLC patients
- Provided written informed consent
- Histologically or cytologically documented ES-SCLC - ES-SCLC defined as; American Joint Committee on Cancer [8th edition] SCLC stage IV
• T any, N any, M1 a/b/c,
or
• T3?4 due to multiple lung nodules that are too extensive or have tumour/nodal volume that is too large to be encompassed in a feasible radiation plan
- ECOG performance-status score of 0 or 1 at registration. Patients with worse performance status (PS) prior to cycle 1 may be included if PS improves to 0-1 prior to cycle 2; these patients would be registered prior to cycle 2
- Life expectancy greater than or equal to 12 weeks at registration
- Brain metastases must be controlled or asymptomatic
- Thoracic disease deemed suitable for radiation therapy following initial systemic therapy
- Bodyweight of at least 30 kg
- Suitability for first-line platinum-based chemotherapy
- Adequate organ and marrow function; and negative pregnancy test for pre-menopausal women
- No prior exposure to immune-mediated therapy including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed cell death-1, anti-programmed cell death ligand-1, and anti-programmed cell death ligand-2 antibodies, excluding therapeutic anticancer vaccines.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Previous high dose radiotherapy to the chest precluding mediastinal radiation
• Significant active or previous autoimmune or inflammatory disorder
• Paraneoplastic syndrome of autoimmune nature requiring systemic treatment
• Interstitial lung disease/pulmonary fibrosis
• History of active primary immunodeficiency
• Uncontrolled, concurrent illness or active infections

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
A single arm of up to 30 evaluable participants given thoracic radiotherapy concurrent with chemo-immunotherapy will be enrolled. Participants not suitable for concurrent thoracic radiotherapy due to field size after cycle 2 may receive sequential radiotherapy. Accounting for a 15% non-evaluable rate, up to 35 participants will be enrolled. An independent data and safety monitoring committee will review the data and assess safety and feasibility following initial 10 participants. As a guide, a toxicity of greater than or equal to Grade 3 oesophageal toxicity in less than or equal to 20% of participants and greater than or equal to grade 3 pneumonitis in less than or equal to 10% would be considered reasonable for progression to a Phase III study. Less than or equal to 20% treatment discontinuation of systematic therapy secondary to radiation toxicities and over 75% participants having disease which can be encompassed within a reasonable radiation portal and complete full dose of radiation therapy is considered feasible.

A second interim analysis will occur after accrual of 20 participants to determine if the trial can be stopped early for meeting the safety requirements. The primary outcome of the study is safety and feasibility and OS will be assessed as secondary endpoints.
A pre-defined subgroup analysis of toxicity will be performed on Group 1 (concurrent thoracic RT) vs Group 2 patients (consolidation thoracic RT).

Recruitment
Recruitment status
Not yet 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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 18482 0
Westmead Hospital - Westmead
Recruitment hospital [2] 18483 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 18484 0
Liverpool Hospital - Liverpool
Recruitment hospital [4] 18515 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 32800 0
2145 - Westmead
Recruitment postcode(s) [2] 32854 0
2148 - Blacktown
Recruitment postcode(s) [3] 32802 0
2170 - Liverpool
Recruitment postcode(s) [4] 32801 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 307577 0
Commercial sector/Industry
Name [1] 307577 0
Astra Zeneca
Address [1] 307577 0
66 Talavera Road, Macquarie Park, NSW 2113
Country [1] 307577 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Trans Tasman Radiation Oncology Group
Address
Calvary Mater Newcastle, MHU Level 5, Edith Street, Waratah, NSW, 2298
Country
Australia
Secondary sponsor category [1] 308404 0
None
Name [1] 308404 0
Address [1] 308404 0
Country [1] 308404 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 307636 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 307636 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Australia

Ethics committee country [1] 307636 0
Australia
Date submitted for ethics approval [1] 307636 0
08/02/2021
Approval date [1] 307636 0
Ethics approval number [1] 307636 0

Summary
Brief summary
This trial aims to determine the safety, feasibility, and efficacy of a combination of chemotherapy, immunotherapy, and chest radiation therapy in extensive stage small cell lung cancer.

Who is it for?
You may be eligible for this study if you are 18 or above and have untreated extensive stage small cell lung cancer.

Study details
Participants will be given durvalumab (an immunotherapy drug) concurrently with 4 cycles of cisplatin/carboplatin and etoposide chemotherapy, which is given as in injection every three weeks over approx. 12 weeks.
Maintenance treatment with durvalumab alone will continue every 4 weeks after the completion of the chemotherapy cycles until there is evidence of disease progression.

Participants will also receive 10 chest radiotherapy sessions, which will take approx. 2 weeks to complete (given either concurrently with cycle 3 or 4 of chemotherapy (called concurrent radiotherapy) or within 6 weeks of finishing chemotherapy (called consolidation radiotherapy). Fractions are expected to be delivered daily. When RT is to start depends on the location and size of the area to be treated).
Throughout the study, participants will be monitored regularly for any adverse effects, and for progression of disease using a number of imaging techniques.

It is hoped that this study may demonstrate that chest radiation is safe and beneficial when given in combination with chemotherapy and immunotherapy for the treatment of extensive stage small cell lung cancer.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107950 0
Dr Eric Hau
Address 107950 0
Blacktown Cancer and Haematology Centre
18 Blacktown Road
Blacktown NSW 2148
Country 107950 0
Australia
Phone 107950 0
+61 2 9881 8421
Fax 107950 0
Email 107950 0
eric.hau@health.nsw.gov.au
Contact person for public queries
Name 107951 0
Ms Rebecca Montgomery
Address 107951 0
Trans Tasman Radiation Oncology Group, of Calvary Mater Newcastle, MHU Level 5, Edith Street, Waratah, NSW, 2298
Country 107951 0
Australia
Phone 107951 0
+61 2 40143911
Fax 107951 0
Email 107951 0
CHESTRT@trog.com.au
Contact person for scientific queries
Name 107952 0
Ms Rebecca Montgomery
Address 107952 0
Trans Tasman Radiation Oncology Group, of Calvary Mater Newcastle, MHU Level 5, Edith Street, Waratah, NSW, 2298
Country 107952 0
Australia
Phone 107952 0
+61 2 40143911
Fax 107952 0
Email 107952 0
CHESTRT@trog.com.au

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 other documents available
Summary results
No Results