Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis (PanGen)
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| ClinicalTrials.gov Identifier: NCT02869802 |
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Recruitment Status :
Recruiting
First Posted : August 17, 2016
Last Update Posted : August 4, 2023
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| Condition or disease | Intervention/treatment |
|---|---|
| Cancer Pancreatic Cancer | Procedure: Tumour Biopsy Other: Serial Collection of Plasma and Serum Samples |
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 |
| Estimated Enrollment : | 190 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | Prospectively Defining Metastatic Pancreatic Ductal Adenocarcinoma Subtypes by Comprehensive Genomic Analysis |
| Actual Study Start Date : | October 6, 2016 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2024 |
| Group/Cohort | Intervention/treatment |
|---|---|
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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. |
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. |
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Archival Cohort
Genomic analyses will be performed on participants' archival tumour samples. Participants will undergo serial collection of plasma and serum samples. |
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. |
- 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.
- 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.
- 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
Biospecimen Retention: Samples With DNA
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, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Probability Sample |
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
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
| Contact: Daniel J Renouf, MD | 6048776000 ext 2445 | drenouf@bccancer.bc.ca |
| Canada, Alberta | |
| Tom Baker Cancer Centre | Recruiting |
| Calgary, Alberta, Canada, T2N 4N2 | |
| Contact: Patricia Tang, MD 403-521-3723 Patricia.Tang@albertahealthservices.ca | |
| Cross Cancer Institute | Withdrawn |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Canada, British Columbia | |
| BC Cancer - Vancouver | Recruiting |
| Vancouver, British Columbia, Canada, V5Z 4E6 | |
| Contact: Daniel J Renouf, MD 6048776000 ext 2445 drenouf@bccancer.bc.ca | |
| Sub-Investigator: Howard Lim, MD | |
| Sub-Investigator: Janine M Davies, MD | |
| Sub-Investigator: Sharlene Gill, MD | |
| Canada, Ontario | |
| The Ottawa Hospital | Active, not recruiting |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| Principal Investigator: | Daniel J Renouf, MD | BC Cancer |
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | British Columbia Cancer Agency |
| ClinicalTrials.gov Identifier: | NCT02869802 |
| Other Study ID Numbers: |
H20-02375 H16-00291 ( Other Identifier: University of British Columbia ) |
| First Posted: | August 17, 2016 Key Record Dates |
| Last Update Posted: | August 4, 2023 |
| Last Verified: | August 2023 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Cancer Pancreatic Cancer Advanced Pancreatic Ductal Adenocarcinoma |
PDAC Genomic Analysis Molecular subtyping |
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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 |