Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000586819
Ethics application status
Approved
Date submitted
11/02/2021
Date registered
18/05/2021
Date last updated
9/08/2024
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
Radiation: Thoracic Radiotherapy
Participants will receive thoracic radiotherapy to a dose of 30 Gray (Gy) in 10 fractions (3 Gy per day) concurrently with cycle 3 or 4 of chemo-immunotherapy (Group 1).
Participants who are unsuitable for concurrent radiotherapy may receive consolidation radiotherapy. Consolidation thoracic radiotherapy will be administered to a dose of 30 Gy in 10 fractions, following 4 cycles of chemo-immunotherapy (Group 2).
Treatment fractions will be delivered daily, where treatment should be completed within 15 days (9-10 fractions a fortnight).

Drug: Etoposide with Carboplatin or Cisplatin (Chemotherapy)
The chemotherapy in this study is a standard treatment for extensive-stage small-cell lung cancer (EC-SCLC). The combination of chemotherapy (etoposide + carboplatin or etoposide + cisplatin) which the participant will receive is dependent on what is standard at the treatment centre.
Chemotherapy will be administered via an intravenous infusion every 3 weeks (21 days) for 4 cycles.

Drug: Durvalumab (Immunotherapy)
The immunotherapy in this study is a standard treatment for ES-SCLC.
Participants will receive a dose of 1500 mg of Durvalumab via an intravenous infusion every 3 weeks (21 days) for 4 cycles, concurrently with chemotherapy.
A 1500 mg maintenance dose of Durvalumab will be administered every 4 weeks after completion of chemotherapy (monotherapy).
Intervention code [1] 319473 0
Treatment: Drugs
Intervention code [2] 319589 0
Treatment: Devices
Comparator / control treatment
There is no control for this study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326203 0
Safety of chemo-immunotherapy with concurrent thoracic radiotherapy:
Group 1 and Group 2 will be compared for the presence of toxicity, whereby the proportion of grade 3 or higher pneumonitis and grade 3 or higher oesophagitis will be monitored using the NCI Common Terminology Criteria for Adverse Events v5.
Timepoint [1] 326203 0
From date of consent to 90 days after trial treatment is discontinued
Primary outcome [2] 326893 0
Feasibility of chemo-immunotherapy with concurrent thoracic radiotherapy:
Group 1 and Group 2 will be compared for the proportion of participants which received concurrent radiotherapy vs the proportion of participants which did not receive concurrent radiotherapy. This will be assessed by the audit of medical records.
The two groups will also be assessed by the proportion of participants in which discontinued thoracic radiotherapy.
Timepoint [2] 326893 0
From date of consent to 90 days after trial treatment is discontinued
Secondary outcome [1] 390504 0
Overall survival:
Overall survival will be defined as the time from Cycle 1 day 1 of chemotherapy until the date of death by any cause. Participants who are alive by the analysis timepoint will be censored at the trial close out date.
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:
Progression free survival will be defined as the time from Cycle 1 Day 1 of chemotherapy until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. Participants who are alive or have not progressed by the analysis time point will be censored at the latest of the dates contributing to a particular overall visit assessment.
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:
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
From date of consent until the date of first documented progression, withdrawal, end of trial, or date of death from any cause, whichever came first
Secondary outcome [4] 423531 0
Time to local failure and local control:
Time to thoracic local failure and proportion of participants with thoracic local control. This will be assessed as a composite secondary outcome where data will be sourced from audit radiology reports.
Timepoint [4] 423531 0
6 and 12 months post intervention commencement

Eligibility
Key inclusion criteria
- Provided written informed consent
- Histologically or cytologically documented ES-ECLC
- Thoracic disease deemed suitable for radiation therapy following initial systemic therapy
- If brain metastases present, then they are to be;
a. asymptomatic without steroid therapy may be included or
b. have required treatment (radiotherapy and/or surgery) and are clinically stable and patient is on a stable or reducing steroid dose of no more than dexamethasone 4mg/day (or equivalent)
- Patients must be considered suitable to receive platinum-based chemotherapy regimen as first-line treatment for ES-SCLC
- ECOG performance-status score of 0 or 1 at registration
- Life expectancy greater than or equal to 12 weeks at registration
- Body weight > 30 kg
- 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
- Adequate organ and marrow function as defined in the Protocol
- Female patients who;
a. are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment
b. are not breast feeding
c. have a negative pregnancy test prior at registration if of child bearing potential or have evidence of non-child bearing potential by fulfilling the criteria as stated in the Protocol at screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Treatment with any of the following:
a. Concurrent chemotherapy (not relevant to patients registered prior to cycle 2who will have received a cycle of platinum/etoposide chemotherapy),investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
b. An investigational product during the last 4 weeks
c. High dose radiotherapy to the chest prior to systemic therapy precluding further thoracic radiation therapy. Radiation therapy outside of the chest for palliative care (i.e., bone metastasis) is allowed but must be completed before first dose of the trial medication
d. Immunosuppressive medication within 14 days before the first dose of Durvalumab. Some exceptions apply
e. Live, attenuated vaccine within 30 days prior to the first dose of Durvalumab
f. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Durvalumab. Surgical procedures to obtain a lung cancer diagnosis or for palliation are allowed
- Medical contraindication to, known allergy or hypersensitivity to Durvalumab, etoposide, carboplatin (patients with allergy/hypersensitivity to carboplatin may receive cisplatin), cisplatin, or any of their excipients
- History of allogeneic organ transplantation
- Has a para-neoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS. Patients with hyponatraemia considered due to SIADH syndrome are eligible
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis. Some exceptions apply
- Interstitial lung disease/pulmonary fibrosis. Patients with emphysema and associated limited areas of pulmonary fibrosis are eligible
- Uncontrolled intercurrent illness
- History of another primary malignancy. Some exceptions apply
- History of leptomeningeal carcinomatosis
- History of active primary immunodeficiency
- Patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Durvalumab

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
Recruiting
Date of first participant enrolment
Anticipated
4/01/2022
Actual
1/02/2022
Date of last participant enrolment
Anticipated
31/08/2024
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
35
Accrual to date
34
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,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 hospital [5] 22966 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [6] 22967 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 24997 0
GenesisCare - St. Vincent's Melbourne - Fitzroy
Recruitment postcode(s) [1] 32800 0
2145 - Westmead
Recruitment postcode(s) [2] 32801 0
3084 - Heidelberg
Recruitment postcode(s) [3] 32802 0
2170 - Liverpool
Recruitment postcode(s) [4] 32854 0
2148 - Blacktown
Recruitment postcode(s) [5] 38271 0
4029 - Herston
Recruitment postcode(s) [6] 38272 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 40654 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 307577 0
Commercial sector/Industry
Name [1] 307577 0
Astra Zeneca
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
Approved
Ethics committee name [1] 307636 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 307636 0
Ethics committee country [1] 307636 0
Australia
Date submitted for ethics approval [1] 307636 0
08/02/2021
Approval date [1] 307636 0
23/06/2021
Ethics approval number [1] 307636 0

Summary
Brief summary
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
[email protected]
Contact person for public queries
Name 107951 0
Courtney Wheeler
Address 107951 0
Trans-Tasman Radiation Oncology Group, Calvary Mater Hospital, Newcastle, MHA Level 5, Edith Street, Waratah, NSW, 2298
Country 107951 0
Australia
Phone 107951 0
+61 2 40143911
Fax 107951 0
Email 107951 0
[email protected]
Contact person for scientific queries
Name 107952 0
Courtney Wheeler
Address 107952 0
Trans-Tasman Radiation Oncology Group, Calvary Mater Hospital, Newcastle, MHA Level 5, Edith Street, Waratah, NSW, 2298
Country 107952 0
Australia
Phone 107952 0
+61 2 40143911
Fax 107952 0
Email 107952 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.