ANZCTR - Registration

Registration number

ACTRN12612000345886

Ethics application status

Approved

Date submitted

21/03/2012

Date registered

26/03/2012

Date last updated

26/03/2012

Type of registration

Retrospectively registered

Titles & IDs

Public title

Circulating Tumour DNA as a Sensitive and Specific Marker of Response to Therapy and of Occult Disease in Colorectal Cancer

Scientific title

Circulating Tumour DNA as a Sensitive and Specific Marker of Response to Therapy and of Occult Disease in Colorectal Cancer

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1129-2961

Trial acronym

Liver Metastasis study

Linked study record

Health condition

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

Patients with resectable colorectal cancer liver metastases

Condition category

Condition code

Cancer

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

Intervention/exposure

Study type

Observational

Description of intervention(s) / exposure

This is a prospective study involving the collection of blood samples for the purposes of measuring circulating DNA from patients with resectable colorectal cancer liver metastases. Two distinct cohorts of patients, those undergoing initial liver resection followed by 12 cycles of FOLFOX and those given pre and postoperative chemotherapy will be treated and followed according to standard protocols.
60 mls of blood will be collected at specified timpoints. - 60 mls will be collected at each timepoint.
COHORT 1 - Initial Surgery the timepoints are:
Timepoint 1 - Screening
Timepoint 2 - 4 weeks post surgery
Timepoint 3 Post cycle 6 adjuvant chemotherapy (Day 1 Cycle 7)
Timepoint 4 - Post cycle 12 (Days 3 at CADD disconnect)
Timepoint 5 - 10 every 3 months (3 mth follow up; 6mth follow up; 12 mth follow up; 18 mth follow up and 24 mth follow up)
COHORT 2 - Pre-op Chemo timpoints are:
Timepoint 1 - Screening
Timepoint 2 - Post cycle 1 (day 1 cycle 2)
Timepoint 3 - Post cycle 2 (day 1 cycle 3)
Timepoint 4 - post cycle 4 (day 1 cycle 5)
Timepoint 5 - 4 weeks post surgery
Timepoint 6 - Post cycle 12 (day 3 at CADD disconnect)
Timepoint 7 -10 - 3 monthly follow - ups ( 3 mths; 6 mths; 9 mths; 12 mnths)
Timepoint 11 & 12 - 6 monthly follow - ups (18 mths and 24 mths)

Intervention code [1]

Not applicable

Comparator / control treatment

This is an exploratory, prospective study enrolling patients diagnosed with colorectal cancer liver metastases to investigate the potential use of a novel blood-based biomarker (circulating tumour DNA) as a sensitive and specific marker of disease response or resistance to chemotherapy and as a marker of residual disease that predicts later recurrence.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To demonstrate that the persistence of tumour DNA in peripheral blood immediately following clinically and radiologically complete resection of liver metastases is a sensitive and specific predictor of subsequent disease recurrence.

Timepoint [1]

Final analysis of blood, plasma and tissue specimens.
COHORT 1 - Initial Surgery the timepoints are:
Timepoint 1 - Screening
Timepoint 2 - 4 weeks post surgery
Timepoint 3 Post cycle 6 adjuvant chemotherapy (Day 1 Cycle 7)
Timepoint 4 - Post cycle 12 (Days 3 at CADD disconnect)
Timepoint 5 - 10 every 3 months (3 mth follow up; 6mth follow up; 12 mth follow up; 18 mth follow up and 24 mth follow up)
COHORT 2 - Pre-op Chemo timpoints are:
Timepoint 1 - Screening
Timepoint 2 - Post cycle 1 (day 1 cycle 2)
Timepoint 3 - Post cycle 2 (day 1 cycle 3)
Timepoint 4 - post cycle 4 (day 1 cycle 5)
Timepoint 5 - 4 weeks post surgery
Timepoint 6 - Post cycle 12 (day 3 at CADD disconnect)
Timepoint 7 -10 - 3 monthly follow - ups ( 3 mths; 6 mths; 9 mths; 12 mnths)
Timepoint 11 & 12 - 6 monthly follow - ups (18 mths and 24 mths)

Secondary outcome [1]

To demonstrate that early changes in circulating tumour DNA levels in patients with measurable disease are a sensitive and specific predictor of response or resistance to systemic chemotherapy compared to CT imaging (cohort 2 only).

Timepoint [1]

Final analysis of blood, plasma and tissue specimens. Central review of CT scan by a radioligist post cycle 1 and cycle 4 completion of chemotherapy.

Secondary outcome [2]

To demonstrate that the persistence of circulating tumour DNA levels (where present after complete surgical resection of all known disease) despite peri-operative or adjuvant therapy predicts subsequent radiologic recurrence.

Timepoint [2]

Final analysis of blood, plasma and tissue specimens. Central review of CT scan by a radioligist post cycle 1 and cycle 4 completion of chemotherapy.

Secondary outcome [3]

To demonstrate that the persistence of circulating tumour DNA levels (where present after complete surgical resection of all known disease) despite peri-operative or adjuvant therapy predicts for worse overall survival.

Timepoint [3]

Final analysis of blood, plasma and tissue specimens. Central review of CT scan by a radioligist post cycle 1 and cycle 4 completion of chemotherapy.

Secondary outcome [4]

To demonstrate that the appearance of circulating tumour DNA when patients are undergoing routine follow-up, where DNA has previously been eradicated by surgery +/- chemotherapy, predicts disease recurrence.

Timepoint [4]

Final analysis of blood, plasma and tissue specimens.
COHORT 1 - Initial Surgery the timepoints are:
Timepoint 1 - Screening
Timepoint 2 - 4 weeks post surgery
Timepoint 3 Post cycle 6 adjuvant chemotherapy (Day 1 Cycle 7)
Timepoint 4 - Post cycle 12 (Days 3 at CADD disconnect)
Timepoint 5 - 10 every 3 months (3 mth follow up; 6mth follow up; 12 mth follow up; 18 mth follow up and 24 mth follow up)
COHORT 2 - Pre-op Chemo timpoints are:
Timepoint 1 - Screening
Timepoint 2 - Post cycle 1 (day 1 cycle 2)
Timepoint 3 - Post cycle 2 (day 1 cycle 3)
Timepoint 4 - post cycle 4 (day 1 cycle 5)
Timepoint 5 - 4 weeks post surgery
Timepoint 6 - Post cycle 12 (day 3 at CADD disconnect)
Timepoint 7 -10 - 3 monthly follow - ups ( 3 mths; 6 mths; 9 mths; 12 mnths)
Timepoint 11 & 12 - 6 monthly follow - ups (18 mths and 24 mths)

Secondary outcome [5]

To demonstrate that the appearance of circulating tumour DNA in patients undergoing routine follow-up in patients where DNA has previously been eradicated by surgery +/- chemotherapy is a more specific and sensitive marker of early recurrence than CEA or imaging.

Timepoint [5]

Final analysis of blood, plasma and tissue specimens. Central review of CT scan by a radioligist post cycle 1 and cycle 4 completion of chemotherapy.

Secondary outcome [6]

To demonstrate that mutations detected in circulating tumour DNA are consistent with those detected in primary and/or metastatic deposits from these patients.

Timepoint [6]

Final analysis of blood, plasma and tissue specimens.
COHORT 1 - Initial Surgery the timepoints are:
Timepoint 1 - Screening
Timepoint 2 - 4 weeks post surgery
Timepoint 3 Post cycle 6 adjuvant chemotherapy (Day 1 Cycle 7)
Timepoint 4 - Post cycle 12 (Days 3 at CADD disconnect)
Timepoint 5 - 10 every 3 months (3 mth follow up; 6mth follow up; 12 mth follow up; 18 mth follow up and 24 mth follow up)
COHORT 2 - Pre-op Chemo timpoints are:
Timepoint 1 - Screening
Timepoint 2 - Post cycle 1 (day 1 cycle 2)
Timepoint 3 - Post cycle 2 (day 1 cycle 3)
Timepoint 4 - post cycle 4 (day 1 cycle 5)
Timepoint 5 - 4 weeks post surgery
Timepoint 6 - Post cycle 12 (day 3 at CADD disconnect)
Timepoint 7 -10 - 3 monthly follow - ups ( 3 mths; 6 mths; 9 mths; 12 mnths)
Timepoint 11 & 12 - 6 monthly follow - ups (18 mths and 24 mths)

Secondary outcome [7]

To demonstrate that where mutations are detected in circulating tumour DNA and recurrent disease is not found that alternative explanations for this finding will include the development of new adenomas or primary colorectal cancers or malignancy at another site.

Timepoint [7]

Final analysis of blood, plasma and tissue specimens.
COHORT 1 - Initial Surgery the timepoints are:
Timepoint 1 - Screening
Timepoint 2 - 4 weeks post surgery
Timepoint 3 Post cycle 6 adjuvant chemotherapy (Day 1 Cycle 7)
Timepoint 4 - Post cycle 12 (Days 3 at CADD disconnect)
Timepoint 5 - 10 every 3 months (3 mth follow up; 6mth follow up; 12 mth follow up; 18 mth follow up and 24 mth follow up)
COHORT 2 - Pre-op Chemo timpoints are:
Timepoint 1 - Screening
Timepoint 2 - Post cycle 1 (day 1 cycle 2)
Timepoint 3 - Post cycle 2 (day 1 cycle 3)
Timepoint 4 - post cycle 4 (day 1 cycle 5)
Timepoint 5 - 4 weeks post surgery
Timepoint 6 - Post cycle 12 (day 3 at CADD disconnect)
Timepoint 7 -10 - 3 monthly follow - ups ( 3 mths; 6 mths; 9 mths; 12 mnths)
Timepoint 11 & 12 - 6 monthly follow - ups (18 mths and 24 mths)

Eligibility

Key inclusion criteria

1. Patients with histologically confirmed primary colorectal cancer
2. Patients with resected primary tumours or planned for curative primary tumour resection.
3. Patients with resectable liver metastases following workup including CT scans of chest, abdomen and pelvis (or MRI if unable to undertake CT scan) and whole body PET scan.
4. Patients fit for surgery
5. Patients fit for combination chemotherapy (5-FU and oxaliplatin)
6. Patients willing to provide written informed consent

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. History of another primary cancer within the last 5 years, with the exception of non-melanomatous skin cancer and carcinoma in situ of the cervix.
2. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the protocol
3. Patients that are not accessible for follow-up

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

18/07/2011

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Ludwig Institute for Cancer Research

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

Ludwig Institute for Cancer Research

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne Health HREC

Ethics committee address [1]

PO 
Royal Melbourne Hospital
Parkville Victoria 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

20/04/2011

Ethics approval number [1]

2011.032

Summary

Brief summary

The purpose of this study is to measure cancer specific gene changes in the blood as a biomarker in monitoring
disease status in colorectal cancer. Biomarkers are substances that can be found in blood and/or tumour tissue
and may be used to measure the effects or progress of a disease or condition.
Genes are substances in the body which contain information about characteristics us as individuals. Previous
studies have found that the majority of colorectal cancers contain mutations in several genes (the gene is changed
or different from the common form) and that these cancerrelated
mutations can be detected in the blood.
Identifying biomarkers are important because they may be linked with disease progression, they may help to identify people who are most likely to benefit from a certain treatment such as chemotherapy, or they may be used to track the status of cancer without the need for invasive procedures, such as biopsies.

Trial website

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Email

Contact person for public queries

Name

Philippa Robertson

Address

PO Box 2008
RMH Post Office
Parkville VIC 3050

Country

Australia

Phone

+61(3)9342 4584

Email

[email protected]

Contact person for scientific queries

Name

Dr Jeanne Tie

Address

PO Box 2008
RMH Post Office
Parkville VIC 3050

Country

Australia

Phone

+61(3) 9342 3037

Email

[email protected]

Trial Review

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