ANZCTR - Registration

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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

7/04/2024

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]

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

Extensive Stage Small Cell Lung Cancer

Lung Cancer

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Intervention code [2]

Treatment: Devices

Comparator / control treatment

There is no control for this study.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

From date of consent to 90 days after trial treatment is discontinued

Primary outcome [2]

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]

From date of consent to 90 days after trial treatment is discontinued

Secondary outcome [1]

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]

Death due to any cause as time to event and proportion at one year and 2 years post intervention commencement

Secondary outcome [2]

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]

Death or disease progression as time to event and proportion at 6 months and 1 year post intervention commencement

Secondary outcome [3]

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]

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]

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]

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?

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

30/09/2027

Actual

Date of last data collection

Anticipated

28/02/2028

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,VIC

Recruitment hospital [1]

Westmead Hospital - Westmead

Recruitment hospital [2]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [3]

Liverpool Hospital - Liverpool

Recruitment hospital [4]

Blacktown Hospital - Blacktown

Recruitment hospital [5]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [6]

Princess Alexandra Hospital - Woolloongabba

Recruitment hospital [7]

GenesisCare - St. Vincent's Melbourne - Fitzroy

Recruitment postcode(s) [1]

2145 - Westmead

Recruitment postcode(s) [2]

3084 - Heidelberg

Recruitment postcode(s) [3]

2170 - Liverpool

Recruitment postcode(s) [4]

2148 - Blacktown

Recruitment postcode(s) [5]

4029 - Herston

Recruitment postcode(s) [6]

4102 - Woolloongabba

Recruitment postcode(s) [7]

3065 - Fitzroy

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Astra Zeneca

Address [1]

66 Talavera Road, Macquarie Park, NSW 2113

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Peter MacCallum Cancer Centre

Ethics committee address [1]

Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

08/02/2021

Approval date [1]

23/06/2021

Ethics approval number [1]

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

https://trog.com.au/trials/trog-20-01-chest-rt/

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Eric Hau

Address

Blacktown Cancer and Haematology Centre
18 Blacktown Road
Blacktown NSW 2148

Country

Australia

Phone

+61 2 9881 8421

Fax

[email protected]

Contact person for public queries

Name

Ryan Davey

Address

Trans-Tasman Radiation Oncology Group, Calvary Mater Hospital, Newcastle, MHA Level 5, Edith Street, Waratah, NSW, 2298

Country

Australia

Phone

+61 2 40143911

Fax

[email protected]

Contact person for scientific queries

Name

Ryan Davey

Address

Trans-Tasman Radiation Oncology Group, Calvary Mater Hospital, Newcastle, MHA Level 5, Edith Street, Waratah, NSW, 2298

Country

Australia

Phone

+61 2 40143911

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

Source	Title	Year of Publication	DOI
Embase	An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer - A Mainstay of Treatment or a Modality in Decline?.	2022	https://dx.doi.org/10.1016/j.clon.2022.08.024
Embase	First-line atezolizumab/durvalumab plus platinum-etoposide combined with radiotherapy in extensive-stage small-cell lung cancer.	2023	https://dx.doi.org/10.1186/s12885-023-10784-8

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically