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Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04469556
Recruitment Status : Recruiting
First Posted : July 14, 2020
Last Update Posted : November 9, 2020
Sponsor:
Collaborators:
Johns Hopkins University
Cold Spring Harbor Laboratory
Ontario Institute for Cancer Research
Dana-Farber Cancer Institute
Memorial Sloan Kettering Cancer Center
Stand Up To Cancer
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:
This is a randomized multicentre phase II trial with a large translational component. The trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal adenocarcinoma. Integrated into this phase II trial are a number of laboratory components including molecular profiling, patient derived organoid establishment, and drug testing sensitivity and other biomarkers.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Metastatic Pancreatic Ductal Adenocarcinoma Advanced Pancreatic Cancer Drug: Folfirinox Drug: Gemcitabine/nab-paclitaxel Phase 2

Detailed Description:

The two chemotherapy regimens GA and mFFX remain standard treatment options without biomarkers to predict response. PASS-01 will for the first time explore progression free survival differences in the two standard backbone regimens used in the advanced setting. Biomarker driven strategies in pancreatic ductal adenocarcinoma (PDAC) are lacking, perhaps accounting for a large number of failed phase II studies. This study will evaluate two standard of care chemotherapy regimens, but will also explore high content molecular profiling, chemotherapy sensitivity signatures, GATA6 and other putative biomarkers as predictors of response to chemotherapy. In addition, the use of patient derived organoid models for personalized medicine in PDAC will continue to develop within this study.

Approximately 150 patients diagnosed with untreated metastatic pancreatic cancer will be randomized to either arm.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Approximately 150 patients will be randomized in a 1:1 ratio to receive one of the two standard of care regimens in patients with confirmed metastatic PDAC
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pancreatic Adenocarcinoma Signature Stratification for Treatment
Actual Study Start Date : October 14, 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Active Comparator: Modified Folfirinox

Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously.

Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Drug: Folfirinox
Chemotherapy
Other Name: Folinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin

Active Comparator: Gemcitabine/nab-Paclitaxel

Gemcitabine/nab-Paclitaxel administered intravenously.

Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Drug: Gemcitabine/nab-paclitaxel
Chemotherapy




Primary Outcome Measures :
  1. Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial. [ Time Frame: 2-4 years ]
    Time from the date of randomization to progression based on the radiology assessment of response using RECIST v1.1, or death, whichever is earlier


Secondary Outcome Measures :
  1. ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA [ Time Frame: 2-4 years ]
    percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)

  2. Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping [ Time Frame: 2-4 years ]
  3. GATA6 as a biomarker of response to mFFX or GA [ Time Frame: 2-4 years ]
  4. • Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics) [ Time Frame: 2-4 years ]
  5. • Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics). [ Time Frame: 2-4 years ]
  6. • Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance [ Time Frame: 2-4 years ]
  7. Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status) [ Time Frame: 2-4 years ]
  8. Cluster Tendency analysis using artificial neural networks and radiomic methods combined [ Time Frame: 2-4 years ]


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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have a histological or radiological diagnosis of untreated metastatic PDAC at screening with histology subsequently confirmed prior to randomization.
  2. Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma.
  3. Patients with a history of prior or concurrent second primary malignancy whose natural history or treatment does not have the potential to interfere with the safety or primary endpoint efficacy assessment of the pancreas cancer should generally be eligible for enrollment in clinical trials.
  4. Age ≥18 years.
  5. Patient must have a tumor lesion that is amenable to a core needle biopsy.
  6. Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen.
  7. Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%).
  8. Life expectancy of greater than 90 days, as judged by the investigator
  9. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  10. Within 14 days of the proposed randomization date, patients must have normal organ and marrow function

Exclusion Criteria:

  1. Patients who have received prior systemic treatment for PDAC, including treatment in the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is permitted.
  2. Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded.
  3. Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures.
  4. Patients with known brain metastases are excluded from participation in this clinical study.
  5. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, inability to stop anticoagulation medication for a biopsy, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
  7. Patients with a known germline mutation in BRCA, PALB2 or other homologous Recombination Repair Deficiency (HRD) genes.
  8. Patients who are pregnant or breastfeeding.
  9. Use (including 'recreational use') of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements. *Use of any illicit drugs or other substance abuse (including alcohol) are not screened in Canada using Toxicity testing. -

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): NCT04469556


Contacts
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Contact: Anna J Dodd 416-946-2399 anna.dodd@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2N9
Contact: Anna Dodd    647-539-6498    anna.dodd@uhn.ca   
Sponsors and Collaborators
University Health Network, Toronto
Johns Hopkins University
Cold Spring Harbor Laboratory
Ontario Institute for Cancer Research
Dana-Farber Cancer Institute
Memorial Sloan Kettering Cancer Center
Stand Up To Cancer
Investigators
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Study Chair: Elizabeth Jaffee, MD Johns Hopkins University
Study Chair: Jennifer J Knox, MD University Health Network, Toronto
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04469556    
Other Study ID Numbers: PASS-01
CAPCR ID: 20-5105 ( Other Identifier: UHN )
First Posted: July 14, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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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
Leucovorin
Gemcitabine
Paclitaxel
Oxaliplatin
Irinotecan
Folfirinox
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents