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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 : August 4, 2023
Sponsor:
Collaborators:
Terry Fox Research Institute
BC Cancer Foundation
Pancreas Centre BC
American Society of Clinical Oncology
Information provided by (Responsible Party):
British Columbia Cancer Agency

Tracking Information
First Submitted Date August 9, 2016
First Posted Date August 17, 2016
Last Update Posted Date August 4, 2023
Actual Study Start Date October 6, 2016
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 13, 2021)		 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 a clinically meaningful timeframe. 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 whose tumours are successfully sequenced.
Original Primary Outcome Measures
 (submitted: August 12, 2016)		 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.
Change History
Current Secondary Outcome Measures
 (submitted: August 12, 2016)
  • 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
  • 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
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 13, 2021)
  • Engraftment rate of patient-derived xenografts [ Time Frame: 5 years ]
  • Success rate of establishing patient-derived organoids [ Time Frame: 5 years ]
  • DNA damage repair pathways [ Time Frame: 5 years ]
    Percentage of patients with somatic or germline alterations in DNA damage repair pathways
  • Hypermutated phenotype [ Time Frame: 5 years ]
    Percentage of patients with a hypermutated phenotype
  • Mismatch repair deficiency [ Time Frame: 5 years ]
    Percentage of patients with mismatch repair deficiency
  • Neo-antigen load [ Time Frame: 5 years ]
    Percentage of patients with a high tumour neo-antigen load
  • Targetable mutations [ Time Frame: 5 years ]
    Percentage of patients with rare but targetable mutations
Original Other Pre-specified Outcome Measures
 (submitted: August 12, 2016)
  • Engraftment rate of patient-derived xenografts [ Time Frame: 5 years ]
  • Success rate of establishing patient-derived organoids [ Time Frame: 5 years ]
  • Percentage of patients with somatic or germline alterations in DNA damage repair pathways [ Time Frame: 5 years ]
  • Percentage of patients with a hypermutated phenotype [ Time Frame: 5 years ]
  • Percentage of patients with mismatch match repair deficiency [ Time Frame: 5 years ]
  • Percentage of patients with a high tumour neo-antigen load [ Time Frame: 5 years ]
  • Percentage of patients with rare but targetable mutations. [ Time Frame: 5 years ]
 
Descriptive Information
Brief Title Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis
Official Title Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis
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.
Detailed Description

This is a prospective non-randomized study of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) undergoing first-line systemic chemotherapy with either folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine and nab-paclitaxel (GP)-based regimens, where tumour samples, baseline and serial blood 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 190 patients will be recruited over the study period. Patients will undergo fresh tumour biopsy at study baseline for comprehensive molecular characterization (biopsy cohort). Patients whose biopsy was unable to undergo whole genome and transcriptome sequencing (e.g. due to insufficient tumour content) 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 and serum samples at baseline and every 4 weeks until end of study. These will be used for exploratory biomarker analyses. Serum cancer antigen 19-9 (CA19-9), also known as carbohydrate antigen 19-9, will also be measured at baseline and every 4 weeks thereafter as part of routine standard of care until end of study. 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 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 from patients in the biopsy cohort 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 will be coordinated with the British Columbia (BC) Cancer Personalized Oncogenomics (POG) program and the data and/or samples shared between the two studies to avoid re-sampling the patient for both POG and PanGen, if the patient is participating in both studies. Molecular analyses will be performed by BC Cancer. Depending on the amount of tumour material obtained from each patient, molecular analyses will be prioritized to first establish or confirm histological diagnosis and then use for whole genome sequencing, whole transcriptome sequencing, proteomics, and patient-derived models.

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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Fresh tumour tissue biopsy samples Archival tumour tissue samples Whole blood samples Plasma samples Serum samples
Sampling Method Probability Sample
Study Population Patients with metastatic PDAC undergoing first-line systemic therapy with either FOLFIRINOX or GP-based regimens.
Condition
  • Cancer
  • Pancreatic Cancer
Intervention
  • 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 and Serum Samples
    Participants will undergo serial collection of plasma and serum samples at baseline and every 4 weeks until end of study.
Study Groups/Cohorts
  • Biopsy Cohort

    Participants will undergo a tumour biopsy at baseline and an optional tumour biopsy at disease progression.

    Participants will undergo serial collection of plasma and serum samples.

    Interventions:
    • Procedure: Tumour Biopsy
    • Other: Serial Collection of Plasma and Serum Samples
  • Archival Cohort

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

    Participants will undergo serial collection of plasma and serum samples.

    Intervention: Other: Serial Collection of Plasma and Serum Samples
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 9, 2018)		 190
Original Estimated Enrollment
 (submitted: August 12, 2016)		 120
Estimated Study Completion Date December 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Histological and/or radiological diagnosis of metastatic PDAC. Patients without a histological diagnosis of PDAC must undergo confirmatory tumour biopsy prior to treatment start date.
  • 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
  • Eastern Cooperative Oncology Group (ECOG) 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
  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Daniel J Renouf, MD 6048776000 ext 2445 drenouf@bccancer.bc.ca
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT02869802
Other Study ID Numbers H20-02375
H16-00291 ( Other Identifier: University of British Columbia )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Current Responsible Party British Columbia Cancer Agency
Original Responsible Party Same as current
Current Study Sponsor British Columbia Cancer Agency
Original Study Sponsor Same as current
Collaborators
  • Terry Fox Research Institute
  • BC Cancer Foundation
  • Pancreas Centre BC
  • American Society of Clinical Oncology
Investigators
Principal Investigator: Daniel J Renouf, MD BC Cancer
PRS Account British Columbia Cancer Agency
Verification Date August 2023