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Trial registered on ANZCTR


Registration number
ACTRN12618000918224
Ethics application status
Approved
Date submitted
21/05/2018
Date registered
31/05/2018
Date last updated
8/02/2019
Date data sharing statement initially provided
8/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Small Cell Lung Carcinoma Trial With Nivolumab and IpiliMUmab in LImited Disease
Scientific title
A Randomised Open-label Phase II Trial of Consolidation With Nivolumab and Ipilimumab in Limited-stage SCLC After Chemo-radiotherapy
Secondary ID [1] 294614 0
NCT02046733
Universal Trial Number (UTN)
Trial acronym
STIMULI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 307447 0
Limited Stage Small Cell Lung Cancer 307448 0
Condition category
Condition code
Cancer 306534 306534 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
During the induction phase patients will receive nivolumab at a dose of 1 mg/kg intravenously followed (on the same day) by ipilimumab at a dose of 3 mg/kg intravenously once every 3 weeks for 4 cycles. This is followed by the maintenance phase. During this phase patients will receive nivolumab 240 mg intravenously once every 2 weeks for a maximum of 12 months from start of maintenance phase (no minimum time for the maintenance phase).
Intervention code [1] 300921 0
Treatment: Drugs
Comparator / control treatment
No Intervention: Observation - no further treatment
Control group
Active

Outcomes
Primary outcome [1] 305540 0
Overall survival
Timepoint [1] 305540 0
From date of randomisation until death from any cause, assessed up to a maximum of 6,5 years
Primary outcome [2] 305541 0
Progression-free survival determined by RECIST 1.1
Timepoint [2] 305541 0
From date of randomisation until documented progression or death, if progression is not documented, assessed up to a maximum of 6,5 years
Secondary outcome [1] 345669 0
Objective response - Objective response is defined as best overall response (CR or PR) across all assessment time-points during the period from randomisation to termination of trial treatment.

Objective response to trial treatment will be determined using RECIST 1.1 criteria
Timepoint [1] 345669 0
From randomisation to termination of trial treatment, up to a maximum of 2 years
CT scans will happen on the following schedule:
• Up to 18 months: every 9 weeks
• Up to 2 years: every 12 weeks


Secondary outcome [2] 345670 0
Time to treatment failure defined by discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death).
Timepoint [2] 345670 0
From date of randomisation until discontinuation of treatment for any reason, assessed up to a maximum of 6.5 years
Secondary outcome [3] 345671 0
Toxicity - toxicity reported by patients and by clinical assessment as assessed through adverse events classified according to NCI CTCAE version 4.
Timepoint [3] 345671 0
During Chemo-radiotherapy AEs will be assessed at baseline and at the end of each cycle of chemo-radiotherapy.
If patient is randomised, AEs will be assessed at randomisation,
Those in the experimental arm: end of each cycle of treatment;
Those in the Observation arm: weeks 9 and 18 and every 18 weeks thereafter;
End of treatment: within 7 days after end-of-treatment visit
100 days period after last treatment / last visit in observation arm.
If patient is not randomised AEs will be assessed at an end-of-treatment visit.
Up to a maximum of 6.5 years
Secondary outcome [4] 347522 0
Objective response to chemo-radiotherapy will be determined by tumour assessment around week 15.
Objective response to trial treatment will be determined using RECIST 1.1 criteria
Timepoint [4] 347522 0
Objective response to chemoradiotherapy this occur around Week 15 (post start of chemoradiotherapy)

Eligibility
Key inclusion criteria
At enrolment:
-Histologically or cytologically confirmed small cell lung carcinoma
-Untreated (with the exception of 1 cycle of chemotherapy given prior to enrolment) limited stage disease (LD) as defined by stage I-IIIB based on 7th TNM classifica-tion (IASLC classification for SCLC proposal). M0 proven by
-Whole body FDG-PET CT including a contrast-enhanced CT of thorax and upper abdomen (incl. liver, kidney, adrenals);
OR contrast-enhanced CT of thorax and upper abdomen (incl. liver, kidney, adrenals) and bone scan; AND
-Brain MRI (or contrast enhanced CT of the brain). Within 28 days before start of chemotherapy
-Age greater than or equal to 18 years
-ECOG performance status 0-1
-Adequate haematological, renal, hepatic and lung function
-Pulmonary function FEV1 of 1.0L or greater than 40% predicted value and DLCO greater than 40% predicted value

At randomisation:
-Chemo-radiotherapy completed per protocol: 4 cycles of chemotherapy, 85% of PTV of thoracic radiotherapy, as well as completed, mandatory PCI
-Non-PD after chemo-radiotherapy and PCI
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria at enrolment:
-Patients with mixed small-cell and non-small-cell histologic features
-Patients with pleural or pericardial effusions proven to be malignant
-Documented history of severe autoimmune or immune mediated symptomatic dis-ease that required prolonged (more than 2 months) systemic immunosuppressive treatment (e.g steroids) such as ulcerative colitis and Crohn´s disease, rheumathoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythemato-sus, or autoimmune vasculitis (eg, Wegener’s granulomatosis)
-Patients with an autoimmune paraneoplastic syndrome requiring concurrent immu-nosuppressive treatment are excluded.
-Interstitial lung disease or pulmonary fibrosis
-Women who are pregnant or in the period of lactation
-Patients with any concurrent anticancer systemic therapy (except for chemotherapy cycle 1)
-HIV, Hepatitis B or Hepatitis C infection
-Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ ductal carcinoma of the breast.
-Previous radiotherapy to the thorax (prior to inclusion)
-Planned mean lung dose greater than 20 Gy or V20 greater than 35%

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)
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 10929 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 10930 0
Westmead Hospital - Westmead
Recruitment hospital [3] 10931 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 10932 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [5] 10933 0
Coffs Harbour Base Hospital - Coffs Harbour
Recruitment hospital [6] 10934 0
Gosford Hospital - Gosford
Recruitment hospital [7] 10936 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [8] 10937 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [9] 10938 0
Riverina Cancer Care Centre - Wagga Wagga
Recruitment hospital [10] 10939 0
Epworth Richmond - Richmond
Recruitment hospital [11] 10940 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [12] 10941 0
Border Medical Oncology - Albury
Recruitment hospital [13] 10942 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [14] 10943 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [15] 10944 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [16] 10945 0
The Townsville Hospital - Douglas
Recruitment hospital [17] 10946 0
Gold Coast University Hospital - Southport
Recruitment hospital [18] 10947 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [19] 10948 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 22704 0
2065 - St Leonards
Recruitment postcode(s) [2] 22705 0
2145 - Westmead
Recruitment postcode(s) [3] 22706 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 22707 0
2050 - Camperdown
Recruitment postcode(s) [5] 22708 0
2450 - Coffs Harbour
Recruitment postcode(s) [6] 22709 0
2250 - Gosford
Recruitment postcode(s) [7] 22711 0
2485 - Tweed Heads
Recruitment postcode(s) [8] 22712 0
2444 - Port Macquarie
Recruitment postcode(s) [9] 22713 0
2650 - Wagga Wagga
Recruitment postcode(s) [10] 22714 0
3121 - Richmond
Recruitment postcode(s) [11] 22715 0
3084 - Heidelberg
Recruitment postcode(s) [12] 22716 0
2640 - Albury
Recruitment postcode(s) [13] 22717 0
3199 - Frankston
Recruitment postcode(s) [14] 22718 0
4029 - Herston
Recruitment postcode(s) [15] 22719 0
4102 - Woolloongabba
Recruitment postcode(s) [16] 22720 0
4814 - Douglas
Recruitment postcode(s) [17] 22721 0
4215 - Southport
Recruitment postcode(s) [18] 22722 0
5042 - Bedford Park
Recruitment postcode(s) [19] 22723 0
7000 - Hobart
Recruitment outside Australia
Country [1] 10295 0
New Zealand
State/province [1] 10295 0

Funding & Sponsors
Funding source category [1] 299233 0
Other Collaborative groups
Name [1] 299233 0
European Thoracic Oncology Platform
Address [1] 299233 0
c/o IBCSG Coordinating Centre,
Effingerstrasse 40,
CH- 3008 Bern
Country [1] 299233 0
Switzerland
Primary sponsor type
University
Name
NHMRC Clinical Trials Centre
Address
The University of Sydney
119-143 Missenden Road,
Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 298503 0
Other Collaborative groups
Name [1] 298503 0
European Thoracic Oncology Platform
Address [1] 298503 0
c/o IBCSG Coordinating Centre,
Effingerstrasse 40,
CH- 3008 Bern
Country [1] 298503 0
Switzerland
Other collaborator category [1] 280066 0
Other Collaborative groups
Name [1] 280066 0
Australasian Lung Cancer Trials Group
Address [1] 280066 0
Australasian Lung Cancer Trials Group
Lung Foundation Australia
Level 2, 11 Finchley Street
Milton, QLD 4064
Country [1] 280066 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300155 0
Royal Prince Alfred Human Research Ethics Committee
Ethics committee address [1] 300155 0
Research Development Office
Royal Prince Alfred Hospital
Camperdown NSW 2050
Ethics committee country [1] 300155 0
Australia
Date submitted for ethics approval [1] 300155 0
22/01/2018
Approval date [1] 300155 0
10/04/2018
Ethics approval number [1] 300155 0
HREC/18/RPAH/5

Summary
Brief summary
The aim of the current study is to investigate whether adding nivolumab and ipilimumab after chemoradiotherapy helps to stop small cell lung cancer coming back.

You may be eligible for this study if you are an adult with confirmed small cell lung carcinoma.

If the study is suitable for you, you will commence treatment with chemotherapy and thoracic (chest) radiotherapy and prophylactic cranial irradiation (PCI/ brain) radiotherapy which are the standard of care treatment for SCLC. Following completion of the chemotherapy and radiotherapy part of your treatment you will have a CT scan to see if your cancer is shrinking or growing. If your cancer has grown your consulting doctor will discuss the most suitable treatment for you at that time.
If your cancer has not grown, you will go on to the next part of the study, and you will be randomised into one of two study groups:

Group 1: Nivolumab plus ipilimumab (experimental treatment)
Group 2: Observation (no further treatment)

If you take part in STIMULI, you will have a number of tests at the first study visit to confirm that the study is suitable for you. At each study visit, you will have various assessments, such as blood testing, urine testing. Computerised Tomography (CT) scans to assess your cancer will be performed every 2-3 months for the first 2 years and then less frequently.

This study will help researchers understand how well this treatment works and how severe the side effects are of the standard treatment (chemotherapy and radiotherapy) alone, compared with the standard treatment (chemotherapy and radiotherapy) followed by immunotherapy (nivolumab and ipilimumab) in patients with limited SCLC.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82722 0
A/Prof Paul Mitchell
Address 82722 0
Austin Hospital
145 Studley Road
Heidelberg, Vic, 3084
Country 82722 0
Australia
Phone 82722 0
+61 2 9562 5000
Fax 82722 0
Email 82722 0
stimuli@ctc.usyd.edu.au
Contact person for public queries
Name 82723 0
Ms Hannora Jurkovic
Address 82723 0
NHMRC Clinical Trials Centre, University of Sydney
119-143 Missenden Road, Camperdown NSW 2050
Country 82723 0
Australia
Phone 82723 0
+61 2 9562 5000
Fax 82723 0
Email 82723 0
stimuli@ctc.usyd.edu.au
Contact person for scientific queries
Name 82724 0
Ms Hannora Jurkovic
Address 82724 0
NHMRC Clinical Trials Centre, University of Sydney
119-143 Missenden Road, Camperdown NSW 2050
Country 82724 0
Australia
Phone 82724 0
+61 2 9562 5000
Fax 82724 0
Email 82724 0
stimuli@ctc.usyd.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will not be made publicly available. It will only be available to selected researchers at the discretion of ETOP. The researcher must make a formal request, which is reviewed by ETOP. The scientific merit and feasibility of each request will be evaluated and the decisions will be taken by ETOP on a case-by-case basis.
What supporting documents are/will be available?
No other documents available
Summary results
No Results