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Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis (PanGen)

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ClinicalTrials.gov Identifier: NCT02869802
Recruitment Status : Recruiting
First Posted : August 17, 2016
Last Update Posted : April 14, 2017
Sponsor:
Collaborators:
Terry Fox Research Institute
BC Cancer Foundation
Pancreas Centre BC
Information provided by (Responsible Party):
British Columbia Cancer Agency

Brief Summary:
Researchers are looking for better ways of understanding and treating pancreatic cancer. The purpose of this study is to see how useful it is to look for changes and characteristics in your genes (molecules that contain instructions for the development and functioning of the cells) and the genes within the tumour. These characteristics may be useful in choosing treatments for patients in the future. Changes (mutations) in genes have been shown to be an important characteristic in cancers. Looking at differences in genes in patients with advanced pancreatic ductal adenocarcinomas and comparing this information with response to their initial chemotherapy treatment may help to learn which treatments may be better for certain patients after initial treatment.

Condition or disease Intervention/treatment
Cancer Pancreatic Cancer Procedure: Tumour Biopsy Other: Serial Collection of Plasma, Serum and Urine Samples

Detailed Description:

This is a prospective non-randomized study of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) undergoing first-line systemic chemotherapy with either FOLFIRINOX or GP-based regimens, where tumour samples, baseline and serial blood and urine samples and standardized clinical and radiological assessments will be obtained. Patients planned for treatment with an investigational agent(s) within a clinical trial using either FOLFIRINOX or GP as the chemotherapy backbone will also be eligible, as long other eligibility criteria for the study are met.

A total of 120 patients will be recruited over 3 years. Patients will undergo fresh tumour biopsy at study enrolment for comprehensive molecular characterization (biopsy cohort). Patients who are unable to undergo biopsy but fulfill all other eligibility criteria will comprise the archival cohort, where limited genomic analyses will be performed on archival tumour samples. Patients with a radiological diagnosis of metastatic PDAC without a confirmatory histological diagnosis may be eligible; in these cases, tumour biopsy for establishing a pathological diagnosis will be given first priority. Remaining tumour samples will be used for research purposes only after the diagnosis of PDAC has been established. In the rare event (<5%) where the histological diagnosis is other than PDAC, patients will be censored from the study and all tumour materials stored for future clinical use outside of this study.

All patients will undergo serial collection of plasma, serum and urine samples at baseline and every 4 weeks until radiological disease progression is confirmed using RECIST 1.1. These will be used for exploratory biomarker analyses. Serum CA19-9 will also be measured at baseline and every 4 weeks thereafter as part of routine standard of care until disease progression is confirmed. In addition, a whole blood sample will be collected at baseline to study germline DNA variants. CT chest, abdomen and pelvis will be performed at baseline and every 8 weeks, with radiological response to therapy assessed using RECIST 1.1.

Patients in the biopsy cohort must have at least one tumour lesion amenable to biopsy from which a minimum of 3 tumour cores can be safely obtainable under CT or ultrasound guidance, as assessed by a staff interventional radiologist. A maximum of 5 tumour cores will be taken from each patient at baseline prior to treatment with FOLFIRINOX or GP. At the time of radiological disease progression, an optional second tumour biopsy will be collected to study changes in the molecular characteristics of tumours under the selection pressure of first-line systemic therapy. This tumour biopsy will be performed using exactly the same procedures described for the baseline biopsy. Tumour biopsies and molecular analyses will be performed through the Personalized Oncogenomics (POG) program of BC (British Columbia) pipeline. Depending on the amount of tumour material obtained from each patient, molecular analyses will be prioritized as described below.

The primary endpoint of PanGen is the generation of molecular and phenotypic signatures of individual tumours in a clinically relevant timeframe. The signature data will be correlated with clinical outcome. One of the key strengths of this cohort approach will be the rigorous annotation of PDAC patients' clinical features and outcomes to all treatments (first-line and other) linked to the molecular profile. The investigators have the potential to be nimble as more data is generated, more hypotheses can be explored and others fine-tuned or eliminated.


Study Type : Observational
Estimated Enrollment : 120 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis
Study Start Date : September 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy
U.S. FDA Resources

Group/Cohort Intervention/treatment
Biopsy Cohort

Participants will undergo a tumour biopsy.

Participants will undergo serial collection of plasma, serum and urine samples.

Procedure: Tumour Biopsy
If there is the presence of a tumour lesion amenable to core needle biopsy as judged by a staff interventional radiologist, a minimum of 3 tumour cores will be obtained under CT or US guidance.
Other: Serial Collection of Plasma, Serum and Urine Samples
Participants will undergo serial collection of plasma, serum and urine samples at baseline and every 4 weeks until radiological disease progression is confirmed using RECIST 1.1.
Archival Cohort

Genomic analyses will be performed on participants' archival tumour samples.

Participants will undergo serial collection of plasma, serum and urine samples.

Other: Serial Collection of Plasma, Serum and Urine Samples
Participants will undergo serial collection of plasma, serum and urine samples at baseline and every 4 weeks until radiological disease progression is confirmed using RECIST 1.1.



Primary Outcome Measures :
  1. Number of days between biopsy and return of comprehensive genomic results. [ Time Frame: An average of 8 weeks ]
    The primary endpoint is the assessment of the feasibility of returning comprehensive genomic results within 8 weeks of the baseline. Specifically the primary endpoint is return of genomic data by 8 weeks from the time of biopsy. This endpoint will be met if the analysis data is available within 8 weeks for 80% of the first 50 patients enrolled in the biopsy cohort. An interim analysis will also be performed to evaluate the quality of fresh tumour biopsy samples.


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Up to an average of 1 year ]
    Response rate defined as the percentage of patients with complete (CR) or partial response (PR) per RECIST 1.1

  2. Disease Control Rate [ Time Frame: Up to an average of 1 year ]
    Disease control rate defined as the percentage of patients who experience CR, PR, or stable disease by RECIST 1.1

  3. Duration of Response [ Time Frame: Up to an average of 1 year ]
    Duration of response defined as the interval between the first date of CR or PR and the earliest date of disease progression or death due to any cause

  4. Progression-Free Survival [ Time Frame: Up to an average of 1 year ]
    Progression-free survival (PFS) defined as the interval between the date of registration and the earliest date of disease progression or death due to any cause

  5. Overall Survival [ Time Frame: Up to an average of 1 year ]
    Overall survival (OS) defined as the interval between the date of registration and the date of death.


Other Outcome Measures:
  1. Engraftment rate of patient-derived xenografts [ Time Frame: 5 years ]
  2. Success rate of establishing patient-derived organoids [ Time Frame: 5 years ]
  3. Percentage of patients with somatic or germline alterations in DNA damage repair pathways [ Time Frame: 5 years ]
  4. Percentage of patients with a hypermutated phenotype [ Time Frame: 5 years ]
  5. Percentage of patients with mismatch match repair deficiency [ Time Frame: 5 years ]
  6. Percentage of patients with a high tumour neo-antigen load [ Time Frame: 5 years ]
  7. Percentage of patients with rare but targetable mutations. [ Time Frame: 5 years ]

Biospecimen Retention:   Samples With DNA
Fresh tumour tissue biopsy samples Archival tumour tissue samples Whole blood samples Plasma samples Serum samples Urine samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients with metastatic PDAC undergoing first-line systemic therapy with either FOLFIRINOX or GP-based regimens.
Criteria

Inclusion Criteria:

  • Histological and/or radiological diagnosis of metastatic PDAC. Patients without a histological diagnosis of PDAC must undergo confirmatory tumour biopsy.
  • Planned for first-line systemic therapy with FOLFIRINOX or GP, either in routine care or in combination with an investigational agent(s) within a clinical trial.
  • Age ≥ 18 years
  • ECOG (Eastern Cooperative Oncology Group) performance status 0-1
  • Adequate organ function
  • Life expectancy of > 90 days as judged by the investigator
  • Ability to give informed consent
  • Measurable disease by RECIST 1.1

Patients in the biopsy cohort must also fulfil the following criteria:

  • Presence of a tumour lesion amenable to core needle biopsy as judged by a staff interventional radiologist. A minimum of 3 tumour cores must be safely obtainable under CT or US guidance.
  • Fit enough to safely undergo a tumour biopsy as judged by the investigator
  • Ability to lie supine for > 60 minutes

Patients in the archival cohort must also fulfil the following criteria:

  • Archival tumour sample available (either a previous tumour diagnostic biopsy or resection specimen)

Exclusion Criteria:

  • Absence of distant or lymph node metastases. Patients with borderline resectable or locally advanced PDAC are not eligible.
  • Received prior systemic therapy (chemotherapy or any other anti-cancer agent) in the advanced setting. Patients who received adjuvant chemotherapy after surgical resection of early stage disease are eligible.
  • Currently receiving anti-cancer therapy (chemotherapy or any other anti-cancer agent)
  • Not fit for combination chemotherapy as judged by the investigator
  • Presence of brain metastases
  • Female patients with positive pregnancy test
  • Patients who are not safe to include in the study as judged by the investigator for any medical or non-medical reason
  • Unable to comply with study assessments and follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02869802


Contacts
Contact: Daniel J Renouf, MD 6048776000 ext 2445 drenouf@bccancer.bc.ca
Contact: Hui-li Wong, MD 6048776000 ext 2445 HuiLi.Wong@bccancer.bc.ca

Locations
Canada, British Columbia
BC Cancer Agency - Vancouver Cancer Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Daniel J Renouf, MD    6048776000 ext 2445    drenouf@bccancer.bc.ca   
Contact: Hui-li Wong, MD    6048776000 ext 2445    HuiLi.Wong@bccancer.bc.ca   
Sponsors and Collaborators
British Columbia Cancer Agency
Terry Fox Research Institute
BC Cancer Foundation
Pancreas Centre BC
Investigators
Principal Investigator: Daniel J Renouf, MD British Columbia Cancer Agency

Additional Information:
Publications:
Canadian Cancer Society's Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2015. Toronto, ON: Canadian Cancer Society; 2015.
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Responsible Party: British Columbia Cancer Agency
ClinicalTrials.gov Identifier: NCT02869802     History of Changes
Other Study ID Numbers: H16-00291
First Posted: August 17, 2016    Key Record Dates
Last Update Posted: April 14, 2017
Last Verified: April 2017

Keywords provided by British Columbia Cancer Agency:
Cancer
Pancreatic Cancer
Advanced Pancreatic Ductal Adenocarcinoma
PDAC
Genomic Analysis
Molecular subtyping

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases