ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12620000087954

Ethics application status

Approved

Date submitted

12/12/2019

Date registered

3/02/2020

Date last updated

16/06/2023

Date data sharing statement initially provided

3/02/2020

Date results information initially provided

18/06/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

LUMOS: Low & Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS – Pilot Study

Scientific title

To perform a pilot study on patients with progressive G2/3 glioma after treatment with radiotherapy and chemotherapy, who consent to resection of tissue for molecular typing or analysis of tissue resected at surgery within six months prior to enrolment, with a view of treatment with matched targeted agents where available, or else treatment with standard of care therapies.

Secondary ID [1]

COGNO 19/05

Secondary ID [2]

CTC 0267

Universal Trial Number (UTN)

Trial acronym

LUMOS

Linked study record

N/A

Health condition

Health condition(s) or problem(s) studied:

Grade 2 glioma (low grade)

Grade 3 glioma (intermediate grade)

Condition category

Condition code

Cancer

Brain

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Patients will undergo molecular testing using a standardised molecular panel (Illumina TruSight 170 panel) to identify mutations for treatment with matched targeted agents where available or treatment with standard of care therapies. Treatments provided to the patient will be at the discretion of the treating physician and monitored for their efficacy. Patients will be reviewed and assessed 8 weekly until disease progression or 2 years after registration to the study. Blood tests and imaging assessments will be collected during the study.

Intervention code [1]

Early Detection / Screening

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Number of patients enrolled

Timepoint [1]

This is defined as the absolute number of patients successfully enrolled for molecular phenotyping over the lifetime of the study

Primary outcome [2]

Number of patients that successfully complete molecular profiling

Timepoint [2]

This is the absolute number of patients for whom molecular profiling was successfully completed over the lifetime of the study

Secondary outcome [1]

Proportion of screened patients enrolled

Timepoint [1]

This is defined as the proportion of patients enrolled compared to those who were screened

Secondary outcome [2]

Proportion of patients that successfully complete molecular profiling

Timepoint [2]

This is defined as the proportion of patients for whom molecular profiling was successfully completed, as a proportion of those who were enrolled

Secondary outcome [3]

Turn-around time (TAT) of molecular screening

Timepoint [3]

This is defined as the time taken from patient consent to central receipt of a completed Molecular Tumour Board Report. In addition, the time from receipt of tumour tissue to a completed Molecular Tumour Board Report will also be measured

Secondary outcome [4]

Matching of Molecular Tumour Board recommendations with pharmaceutical agents. Results from the Molecular Tumour Board Report will be reviewed by a panel of experts who will make recommendations based on the results of the molecular testing and these will be provided to the treating doctor.

Timepoint [4]

This is the absolute number of patients with actionable mutations detected on molecular profiling with targeted agents, either through a clinical trial, compassionate access, hospital supply, or pharmaceutical access programmes

Secondary outcome [5]

The proportion of patients in whom a Molecular Tumour Board recommended pharmaceutical agent is obtained will be assessed through reporting of treatment and follow-up information to the LUMOS study by the treating physician at each instance that the participant comes in for a treatment visit or assessment. The treating doctor will discuss results from the Molecular Tumour Board Report with the participant and both will jointly decide which of the available treatments the participant wishes to undertake.

Timepoint [5]

This is the proportion of patients in whom a pharmaceutical targeted agent is obtained and used, either through a clinical trial, compassionate access, hospital supply, or pharmaceutical access programmes

Secondary outcome [6]

Response to any Molecular Tumour Board recommended pharmaceutical agent. The response to a recommended pharmaceutical agent will be measured by follow-up visits every two months for 24 months following delivery of the molecular tumour board report or as directed by the treating physician based on the schedule of the treatment received, clinical trial protocol, special access scheme, or standard of care at site. At each follow-up visit, a clinic assessment, blood tests and an MRI will be performed to assess response to pharmaceutical agents. If the patient transfers to another site for treatment, then follow-up information (including MRI results) will be captured remotely.

Timepoint [6]

Key clinical outcomes (response and duration of response, time to progression, overall survival as measured by Progression Free Survival at 12 months) will be measured by follow-up visits every two months for 24 months following delivery of the molecular tumour board report or as directed by the treating physician based on the schedule of the treatment received, clinical trial protocol, special access scheme or standard of care at site. At each follow-up visit, a clinic assessment, blood tests and an MRI will be performed to assess response to pharmaceutical agents.

Secondary outcome [7]

Number of patients who undergo further surgical debulking at time of disease progression whilst participating in LUMOS

Timepoint [7]

This is the number of patients participating in LUMOS who are deemed suitable for second debulking surgery at the time of disease progression. This is at the discretion of the Treating Physician. Follow-up visits to assess progression to disease will be performed every two months for 24 months following delivery of the molecular tumour board report or as directed by the treating physician based on the schedule of the treatment received, clinical trial protocol, special access scheme or standard of care at site. At each follow-up visit, a clinic assessment, blood tests, and an MRI will be performed. Follow-up information will be reported for the LUMOS study.

Secondary outcome [8]

The number of patients who were screened for the study

Timepoint [8]

This is the number of patients screened to confirm eligibility for the study

Secondary outcome [9]

Response to clinician recommended pharmaceutical agent

Timepoint [9]

Key clinical outcomes (response and duration of response, time to progression, overall survival as measured by Progression Free Survival at 12 months) will be recorded.

Eligibility

Key inclusion criteria

1. Adults, aged 18 years and older, with histological confirmed grade 2 or 3 glioma at initial diagnosis.
2. Prior to last craniotomy and surgery, evidence of progressive disease as defined as evidence of new contrast-enhancing tumour and/or 25% increase in the size of the T2/FLAIR area compared to prior imaging after prior treatment with radiotherapy and chemotherapy.
3. Has available tissue from resection for progressive disease for molecular profiling either within 6 months of study enrolment or following enrolment.
4. For patients who are undergoing standard of care surgery at the time of study entry:
a. The patient must be suitable for craniotomy as the opinion of the neurosurgical team who will perform the surgery.
b. In the opinion of the neurosurgical team, it will be possible to safely undertake a debulking procedure and that sufficient tissue will be obtained for molecular testing
c. Has substantially recovered from their surgical resection, as evidenced by having no major on-going safety issues (e.g. infection requiring antibiotics)
5. Patients who have already undergone standard of care surgery less than or equal to 6 months prior to study registration, there must be sufficient tissue available for molecular testing and the patient must not have had intervening anti-cancer therapy.
6. Dose at registration must be less than or equal to 20mg prednisolone or less than or equal to 3 mg dexamethasone daily (or equivalent). Patients who are not on steroids are preferred for study participation.
7. ECOG performance status 0-2.
8. Has measurable disease post their last craniotomy that is suitable for repeat assessment by MRI scans.
9. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
10. Signed, written informed consent (main study and tissue banking).

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Glioma tissue for molecular pathology obtained greater than or equal to 6 months prior to study entry
2. Any intervening systemic therapy or radiotherapy between most recent imaging showing progressive disease and study enrolment
3. Patients who have had intra-surgical treatments (e.g. oncolytic virus administration, Gliadel wafers) at their last craniotomy prior to study enrolment
4. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
5. Subjects unable (e.g. due to pacemaker or ICD device) or unwilling to have a contrast-enhanced MRI of the head.
6. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

Study design

Purpose

Screening

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

This is a pilot study and no formal sample size calculation was undertaken. It is expected that the pilot will contain 5 sites and approximately 10 patients in the 12 months period.

The following variables will be presented using standard summary statistics. No formal statistical analysis is planned.
Recruitment:
• The number of eligible grade 2/3 glioma patients will be obtained from site screening logs and described separately at each site and overall.
• The number and percentage of these patients who are enrolled on LUMOS will be described separately at each site and overall.
• Demographic and clinical characteristics of enrolled patients will be summarised.
Molecular screening:
• The number and percentage of enrolled patients for whom tissue was successfully screened using molecular profiling
• Reasons for not undergoing molecular screening and for unsuccessful screening.
• In patients for whom a molecular screening report is received, the median (range) time from time of consent and from time that laboratory received the tissue, to the time of receipt of the report by the Treating Physician.
• In patients for whom a molecular screening report is received, number of targets identified that match molecular targeted agents currently accessible through clinical trials or pharmaceutical access programs.
• In patients for whom a target was identified, whether or not treatment plan was subsequently changed, and reasons for changing/not changing the plan.
• In patients for whom a target was identified, the proportion who received a targeted agents as a result of the MTB recommendation
Clinical outcomes:
• The number and percentage of enrolled patients who experience disease progression while participating on LUMOS, and the number and percentage of these who then undergo further debulking
• The number and percentage of patients who achieve tumour response, and the median (range) duration of response
• Overall and progression-free survival will be described using the Kaplan-Meier method

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

31/03/2020

Actual

1/05/2020

Date of last participant enrolment

Anticipated

31/03/2021

Actual

21/01/2021

Date of last data collection

Anticipated

31/03/2023

Actual

31/05/2021

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,WA,VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [2]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [3]

St Vincent's Hospital (Darlinghurst) - Darlinghurst

Recruitment hospital [4]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [5]

Sir Charles Gairdner Hospital - Nedlands

Recruitment postcode(s) [1]

3084 - Heidelberg

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment postcode(s) [3]

2010 - Darlinghurst

Recruitment postcode(s) [4]

4029 - Herston

Recruitment postcode(s) [5]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Medical Research Future Fund

Address [1]

Sirius Building, 23 Furzer Street, Woden Town Centre, ACT 2606

Country [1]

Australia

Primary sponsor type

University

Name

NHMRC Clinical Trials Centre (CTC), University of Sydney

Address

The University of Sydney (USYD), City Rd, Darlington New South Wales 2008

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Other Collaborative groups

Name [1]

Cooperative Trials Group for Neuro-Oncology

Address [1]

NHMRC Clinical Trials Centre
Level 6, Lifehouse
119-143 Missenden Road
Camperdown, NSW 2050

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Prince Alfred Hospital Ethics committee

Ethics committee address [1]

Suite 210A
RPA Medical Centre
Cnr Missenden Road and Carillon Avenue
NEWTOWN NSW 2042

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

16/09/2019

Approval date [1]

27/11/2019

Ethics approval number [1]

X19-0383 and 2019/ETH12848

Summary

Brief summary

This study aims to evaluate a new approach to provide a ‘personalised’ treatment management plan for patients with glioma that has started to grow again following treatment with radiotherapy and chemotherapy.

Who is it for?
You may be eligible to join this study if you are aged 18 years or older, with histological confirmed grade 2 or 3 glioma at initial diagnosis. In addition, evidence of progressive disease as defined as evidence of new contrast-enhancing tumour and/or 25% increase in the size of the T2/FLAIR area compared to prior imaging after prior treatment with radiotherapy and chemotherapy.

Study details
For each participant, the study will involve a taking a sample of tumour tissue during surgery and then screened for a range of biomarkers. If a suitable biomarker is found, the study team will try and match the identified biomarker with specific treatment. Blood samples and imaging assessments will also be obtained during this study.

It is hoped that screening tumour tissue for specific biomarkers can inform a personalised treatment plan for patients with brain cancer and provide valuable insight to the feasibility of conducting such trials.

Trial website

https://www.cogno.org.au/content.aspx?page=currenttrials

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Hui Gan

Address

NHMRC Clinical Trials Centre
The Lifehouse Building, Level 6,
119-143 Missenden Road
Camperdown, NSW, 2050

Country

Australia

Phone

+61 2 9562 5000

Fax

[email protected]

Contact person for public queries

Name

Dr LUMOS Trial Operations Coordinator

Address

NHMRC Clinical Trials Centre
The Lifehouse Building, Level 6,
119-143 Missenden Road
Camperdown, NSW, 2050

Country

Australia

Phone

+61 2 9562 5000

Fax

[email protected]

Contact person for scientific queries

Name

Dr LUMOS Trial Operations Coordinator

Address

NHMRC Clinical Trials Centre
The Lifehouse Building, Level 6,
119-143 Missenden Road
Camperdown, NSW, 2050

Country

Australia

Phone

+61 2 9562 5000

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

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Conference poster	No		Poster titled "Low and Intermediate Grade Glioma U... [More Details]

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	LUMOS - Low and Intermediate Grade Glioma Umbrella Study of Molecular Guided TherapieS at relapse: Protocol for a pilot study.	2021	https://dx.doi.org/10.1136/bmjopen-2021-054075

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

Trial Review

Documents added manually

Documents added automatically