ANZCTR - Registration

Registration number

ACTRN12616000519459

Ethics application status

Approved

Date submitted

14/04/2016

Date registered

21/04/2016

Date last updated

24/03/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Biomarkers in Pancreatic Cancer

Scientific title

Assessing Predictive and Prognostic Biomarkers in Pancreatic Cancer

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1181-4421

Trial acronym

Linked study record

Health condition

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

Histologically or cytologically confirmed pancreatic cancer

Condition category

Condition code

Cancer

Pancreatic

Intervention/exposure

Study type

Observational

Description of intervention(s) / exposure

Potential subjects with pancreatic cancer may be identified at pre-admission or outpatient clinic by a clinician or VCB research coordinator, and if consent is obtained tissue, blood and/or urine sample will be collected. All patients will be treated as per standard of care. The only procedure beyond standard of care is the collection of tissue, blood and/or urine samples.

Blood and/or urine samples will be collected at the time of other standard-care assessments (such as CEA) to minimise/eliminate the need for additional venipunctures.

Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Archival tissue specimens will be requested for each patient after enrolment. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures,

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To explore and validate novel prognostic and predictive biomarkers in pancreatic cancer.

This will be achieved using molecular analyses to identify changes in gene/ protein expression, identify mutations, or amplifications of genes that may be important in pancreatic cancer tumour prognosis and response to therapy.

Some examples of molecular techniques that may be used include:
1. Immunohistochemistry to identify expression of proteins.
2. Western blot analysis for phosphorylation status.
3. Multiplexed microarrays, used to determine relative expression changes
4. Quantitative PCR, used to test for RNA, microRNA expression and measure copy numbers of genes and determine relative expression changes
5. Next generation sequencing, used to determine mutations present in pancreatic cancer

Timepoint [1]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Primary outcome [2]

To explore and validate novel diagnostic and monitoring methods in pancreatic cancer.

This will be achieved using molecular analyses to identify changes in gene/ protein expression, identify mutations, or amplifications of genes that may be important in pancreatic cancer tumour prognosis and response to therapy.

Some examples of molecular techniques that may be used include:
1. Immunohistochemistry to identify expression of proteins.
2. Western blot analysis for phosphorylation status.
3. Multiplexed microarrays, used to determine relative expression changes
4. Quantitative PCR, used to test for RNA, microRNA expression and measure copy numbers of genes and determine relative expression changes
5. Next generation sequencing, used to determine mutations present in pancreatic cancer

Timepoint [2]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Primary outcome [3]

To explore how novel biomarkers can improve development of new drugs and/or combinations of drugs to treat pancreatic cancer.

This will be achieved using molecular analyses to identify changes in gene/ protein expression, identify mutations, or amplifications of genes that may be important in pancreatic cancer tumour prognosis and response to therapy.

Some examples of molecular techniques that may be used include:
1. Immunohistochemistry to identify expression of proteins.
2. Western blot analysis for phosphorylation status.
3. Multiplexed microarrays, used to determine relative expression changes
4. Quantitative PCR, used to test for RNA, microRNA expression and measure copy numbers of genes and determine relative expression changes
5. Next generation sequencing, used to determine mutations present in pancreatic cancer

Timepoint [3]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [1]

To explore the correlation between novel tissue and blood-based biomarker and recurrence and survival outcomes in pancreatic cancer, i.e. the prognostic impact of the biomarker.

Correlation between fresh primary tumour specimen and blood biomarkers with recurrence and survival as assessed by data linkage to clinical data.

Timepoint [1]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [2]

To correlate changes in tissue and blood-based biomarkers with those detected in primary and/or metastatic tissue from the same patient

Timepoint [2]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [3]

To determine if circulating tumour DNA can be used in the diagnosis of pancreatic cancer and in the monitoring of patient response.

This will be achieved by correlation of ctDNA assay results from blood sample analyses with gold standard diagnostic marker (CA 19-9), and with patient response to treatment, as assessed by data linkage to clinical data.

Timepoint [3]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [4]

To explore the correlation between tissue and blood-based biomarker and clinical outcomes (e.g. response rate, progression-free survival and overall survival) according to treatment received, i.e. can certain biomarkers predict for therapy response, as assessed by data linkage to clinical data.

Timepoint [4]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [5]

To assess the dynamic changes in tissue and blood-based biomarkers in response to cytotoxic chemotherapies, and/or molecularly targeted therapies, and/or biologic agents

Timepoint [5]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [6]

To determine if early changes in blood-based biomarkers are a sensitive and specific predictor of response or resistance to systemic chemotherapy and/or biologic agents compared to CT imaging.

Timepoint [6]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Secondary outcome [7]

To identify new drugs and/or combinations of drugs that target multiple cascades within a patient’s pancreatic tumour, in order to design combination treatment strategies that will overcome the complication of numerous genetic mutations. This will be achieved by review of blood and urine biomarker changes over time and in response to different treatment types.

Timepoint [7]

Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Eligibility

Key inclusion criteria

1. Male and female
2. At least 18 years of age
3. Patients with histologically or cytologically confirmed pancreatic cancer.
4. Able to provide archival tumour specimen for molecular analysis
5. Accessible for follow up and data collection
6. Able and willing to provide informed consent for any blood and urine collection above standard of care. Able to provide written, voluntary and informed consent for blood and/or urine collection

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. No archival tissue specimen available for molecular analysis
2. Medical or psychiatric condition or occupational responsibilities that may preclude compliance with the tissue collection protocol
3. Females who are pregnant

Study design

Statistical methods / analysis

This protocol aims to identify prognostic and predictive biomarkers. The proposed study size includes 500 patients. Assuming alpha of 0.05, the number of patients enrolled into this protocol is sufficient to identify a biomarker that predicts for recurrence in greater than 40% of patients, with power of 0.8.

Descriptive statistics will be used to analyse data arising directly from this protocol study. The Kaplan-Meier method and the Mantel-Cox log-rank test will be used for survival analyses. Proportions will be compared using the Chi square method or Fisher’s exact test. For all analyses, two-sided p values of < 0.05 were considered significant. Multivariate survival analyses will use the Cox Proportional Hazards method.

Using multivariate analyses will allow for detection of prognostic biomarkers while minimising impact of selection and information biases. Selection bias for predictive biomarkers are minimised by the fact that only patients who have received each particular treatment will be included in the analysis, and in Australia, each treatment is only available at certain points during a patient’s disease course.

Further statistical methodology and calculations will be provided for each specific project that wishes to analyse aspects of this data and tissue set. The results of the various assays will be collated and analysed. The results of the biomarker studies will be examined statistically to determine the specificity and sensitivity of single or any combination of markers in detecting the presence of Pancreatic ductal adenocarcinoma (PDAC), predicting recurrence risk and response/resistance to treatment. As these studies are exploratory and observational with no treatment intervention, no formal statistical hypothesis will be tested.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/06/2017

Actual

Date of last participant enrolment

Anticipated

1/05/2026

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

500

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [2]

Western Hospital - Footscray

Recruitment hospital [3]

Sunshine Hospital - St Albans

Recruitment hospital [4]

Box Hill Hospital - Box Hill

Recruitment postcode(s) [1]

3050 - Royal Melbourne Hospital

Recruitment postcode(s) [2]

3011 - Footscray

Recruitment postcode(s) [3]

3021 - St Albans

Recruitment postcode(s) [4]

3128 - Box Hill

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

The Walter and Eliza Hall Institute of Medical Research

Country [1]

Australia

Primary sponsor type

Other Collaborative groups

Name

The Walter and Eliza Hall Institute of Medical 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]

Date submitted for ethics approval [1]

09/03/2016

Approval date [1]

23/03/2016

Ethics approval number [1]

HREC/16/MH/30

Summary

Brief summary

Pancreatic cancer is a devastating disease that is set to become the 2nd leading cause of cancer-related deaths worldwide by 2020. Over 80% of pancreatic cancer patients are diagnosed with unresectable locally advanced or metastatic disease.

Through data collection and correlation with analyses of archival tumour specimens and blood collections, this trial aims to identify and validate novel diagnostic and monitoring methods; novel predictive and prognostic biomarkers and to use these to inform studies of novel therapeutic opportunities that will improve the management of pancreatic cancer.

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, and have been diagnosed with pancreatic ductal adenocarcinoma (PDAC).

Study details
This protocol aims to enrol at least 500 consecutive eligible patients over 10 years. Enrolled patients will undergo collection of clinical data and archival tumour specimens. Where applicable, patients will also undergo collection of blood and/ or urine at several time points. Once a sufficient cohort has been enrolled, selected molecular analyses will be conducted on each specimen, thus, allowing for batching of specimens.
Enrolled patients will undergo collection of clinical data and archival or fresh tumour specimens as part of routine clinical management, with all patients will be treated as per standard of care.

When applicable, archival tissue samples from the primary pancreatic cancer, matched normal pancreas tissue and/or resected metastases will be obtained, upon enrolment. to study. Where possible, current biopsy specimens (fresh tissue) will be collected by either Victorian Cancer Biobank or local pathology laboratories at the time of standard of care procedures.

Patients that consent to the “liquid biopsy” (blood and urine collection) sub-study will undergo collection of blood/plasma and urine at the beginning and during each systemic therapy. Blood (upto 60 ml) and urine (upto 60 ml) will be collected for research purposes on the following occasions:

1. Before and after surgical removal of pancreatic cancer (if applicable)
2. Before and after any chemotherapy regimen (if applicable)
3. Every 6 months while you are on active surveillance (if applicable)

Follow up will occur until the end of active surveillance, death or 5 years post enrolment, whichever occurs first.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Belinda Lee

Address

Gibbs Lab
Systems Biology and Personalised Medicine Division
The Walter and Eliza Hall Institute of Medical Research
1G Royal Pde
Parkville
VIC
3052

Country

Australia

Phone

+61 3 93452893

Email

[email protected]

Contact person for public queries

Name

Mr Siavash Foroughi

Address

Gibbs Lab
Systems Biology and Personalised Medicine Division
The Walter and Eliza Hall Institute of Medical Research
1G Royal Pde
Parkville
VIC
3052

Country

Australia

Phone

+61 3 9345 2894

Email

[email protected]

Contact person for scientific queries

Name

Dr Belinda Lee

Address

Gibbs Lab
Systems Biology and Personalised Medicine Division
The Walter and Eliza Hall Institute of Medical Research
1G Royal Pde
Parkville
VIC
3052

Country

Australia

Phone

+61 3 93452893

Email

[email protected]

Trial Review

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