ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12622001037796

Ethics application status

Approved

Date submitted

18/07/2022

Date registered

25/07/2022

Date last updated

30/10/2024

Date data sharing statement initially provided

25/07/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

TIPTOE - Investigating Peripheral T cell Tolerance in Colorectal Cancer

Scientific title

TIPTOE - Investigating Peripheral T cell Tolerance in Colorectal Cancer

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1280-4151

Trial acronym

TIPTOE

Linked study record

Health condition

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

Colorectal Cancer

Condition category

Condition code

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Individuals with stage IV colorectal cancer who are planned to undergo surgery to remove their primary tumour +/- metastatic disease as part of their routine cancer care will be recruited to this study. At the time of surgery, once the specimen has been surgically resected, a number of fresh tissue samples will be obtained from the specimen for the research study. These samples will include lymph nodes, a small sample of the primary tumour, a sample of normal tissue, and a sample of a metastasis. These samples will be obtained by a senior colorectal surgeon under the supervision of pathology staff. In addition, a blood sample (up to 40ml) will be taken from the participant via their routinely inserted peripheral vein cannula once the participant is under general anaesthesia or at the appropriate time prior to surgery co-ordinated with diagnostic sampling by the anaesthetist.

Samples obtained will be processed for single cell RNA sequencing analysis. Remaining tissue, cells and plasma that have been isolated from tissue and blood will be cryopreserved and stored in a secure manner.

Participants will not be required to attend any follow up study visits for this study. The Peter MacCallum Cancer Centre hospital electronic medical record will be reviewed from time of initial diagnosis up to 3 years post-surgery for all participants who choose to enrol. Only relevant clinical data regarding the participant will be obtained and stored in a secure and de-identified manner. This will include basic demographics, diagnosis, stage and site of primary tumour, site(s) of metastatic disease, prior anti-cancer treatment, relapse date, death date and follow up dates, past and concurrent medical history, and concurrent medications at time of surgery.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Identification of a lymph node restricted CD8+ T cell population with a gene expression profile consistent with peripheral tolerance using single cell RNA sequence (scRNAseq) analysis of all obtained samples.

Timepoint [1]

At completion of scRNAseq analysis of all obtained samples

Secondary outcome [1]

Frequency of tolerant CD8+ T cells in the tumour draining lymph node assessed by scRNAseq analysis of all obtained samples

Timepoint [1]

At completion of scRNAseq analysis of all obtained samples

Secondary outcome [2]

Relapse-free survival defined by time (months) from surgery to colorectal cancer recurrence stratified by the frequency of tolerant CD8+ T cells in the tumour draining lymph node assessed by scRNAseq analysis of all obtained samples.

Timepoint [2]

Relapse-free survival will be censored for all enrolled participants at the time of completion of scRNAseq analysis of all obtained samples.

Secondary outcome [3]

Overall survival defined by time (months) from colorectal cancer diagnosis to death from any cause stratified by the frequency of tolerant CD8+ T cells in the tumour draining lymph node assessed by scRNAseq analysis of all obtained samples.

Timepoint [3]

Overall survival will be censored for all enrolled participants at the time of completion of scRNAseq analysis of all obtained samples

Secondary outcome [4]

Frequency of tolerant CD8+ T cells in the tumour draining lymph node assessed by scRNAseq analsysis stratified by tumour microsatellite status determined by routine immunohistochemistry.

Timepoint [4]

At completion of scRNAseq analysis of all obtained samples

Secondary outcome [5]

Frequency of tolerant CD8+ T cells in the tumour draining lymph node, assessed by scRNAseq, stratified by the frequency of tumour immune-cell infiltration, assessed by scRNAseq and immunohistochemistry analysis of all obtained samples.

Timepoint [5]

At completion of scRNAseq analysis of all obtained samples.

Secondary outcome [6]

Identification of a lymph node restricted tolerant CD8+ T cell population using snPATHOseq, Visium HD or Opal immunohistochemistry analysis of formalin-fixed paraffin embedded samples of all obtained tissue samples.

Timepoint [6]

At completion of snPATHOseq, Visium HD or Opal immunohistochemistry analysis of formalin-fixed paraffin embedded samples of all obtained tissue samples.

Eligibility

Key inclusion criteria

1. Subjects must have voluntarily provided written informed consent for the study.
2. Subjects must be at least 18 years of age at the time of consent.
3. Subject must have histologically confirmed or suspected colorectal adenocarcinoma.
4. Subjects must have stage IV disease based on the AJCC Cancer Staging Manual 8th edition.
5. Subjects must be undergoing surgical resection of their primary tumour at the Peter
MacCallum Cancer Centre as part of their routine oncological care.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Subjects unable to voluntarily provide written informed consent.
2. Subjects with stage I-III colorectal cancer.
3. Any medical or psychosocial reason that in the opinion of the investigator would make
the subject inappropriate for the study.

Study design

Purpose

Duration

Selection

Timing

Prospective

Statistical methods / analysis

This is an exploratory study and no formal sample size calculation has been performed. The sample size of 25 subjects is a product of projected recruitment numbers within 2 years and available funding.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/08/2022

Actual

21/09/2022

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)

VIC

Recruitment hospital [1]

Peter MacCallum Cancer Centre - Melbourne

Recruitment postcode(s) [1]

3000 - Melbourne

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

AstraZeneca Research Grant

Address [1]

AstraZeneca Pty Ltd
P.O. Box 131
North Ryde NSW 1670

Country [1]

Australia

Primary sponsor type

Hospital

Name

Peter MacCallum Cancer Centre

Address

305 Grattan St
Melbourne
VIC 3000

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 Human Research Ethics Committee

Ethics committee address [1]

305 Grattan St
Melbourne
VIC 3000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/06/2022

Approval date [1]

27/06/2022

Ethics approval number [1]

HREC/85604/PMCC

Summary

Brief summary

Colorectal cancer can develop in the colon (large bowel) and/or rectum. If left undetected, it can spread to lymph nodes and other organs in the body in a process called metastasis. It is thought that the immune system plays a role in preventing some cancers from growing or spreading. However, we do not fully understand why the immune system fails to prevent all cancers. New therapies called ‘immunotherapy’ have been developed that target the immune system in order to treat cancer once it is detected. Unfortunately, this type of treatment does not work well for most individuals with colorectal cancer.
This project aims to investigate whether an immune system process called ‘tolerance’ may explain why the immune system fails to prevent colorectal cancer from growing and spreading. The project also aims to investigate whether ‘tolerance’ may explain why immunotherapy is not effective for most individuals with colorectal cancer.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with a stage 4 colorectal cancer and you have been scheduled to undergo surgery to remove your primary tumour, lymph nodes and other affected sites as part of your cancer treatment.

Study details
If you choose to enrol in this study, you agree that the study investigators may take samples from the tumour, lymph nodes, blood and other affected tissues for this study. Participants will also be asked to grant permission for the investigators to review and collect details of their medical history from their records. The investigators will then complete a series of analyses on the samples to determine whether 'tolerant' cells are present and may explain why immunotherapy does or does not work against these cancers.

It is hoped that knowledge gained from this project may contribute to the development of new and better treatments for individuals with colorectal cancer in the future.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Ian Parish

Address

Cancer Immunology Program
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne
VIC 3000

Country

Australia

Phone

+61 3 85595815

Fax

Ian.Parish@petermac.org

Contact person for public queries

Name

Avraham Travers

Address

Peter MacCallum Cancer Centre
305 Grattan St
Melbourne
VIC 3000

Country

Australia

Phone

+61 3 85595816

Fax

Avraham.Travers@petermac.org

Contact person for scientific queries

Name

Ian Parish

Address

Cancer Immunology Program
Peter MacCallum Cancer Centre
305 Grattan St
Melbourne
VIC 3000

Country

Australia

Phone

+61 3 85595815

Fax

Ian.Parish@petermac.org

Data sharing statement

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

Yes

What data in particular will be shared?

All clinical and biological data, after de-identification

When will data be available (start and end dates)?

Following publication, no end date.

Available to whom?

Researchers who provide a methodologically sound proposal, case-by-case basis at the discretion of the Primary Sponsor

Available for what types of analyses?

Any purpose

How or where can data be obtained?

Access subject to approvals by Principal Investigator and Primary Sponsor.
Contact via email: Ian.Parish@petermac.org

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.

Trial Review

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