Clinical Trials /

Pancreatic Adenocarcinoma Signature Stratification for Treatment

NCT04469556

Description:

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.

Related Conditions:
  • Pancreatic Adenosquamous Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Pancreatic Mucinous-Cystic Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pancreatic Adenocarcinoma Signature Stratification for Treatment
  • Official Title: Pancreatic Adenocarcinoma Signature Stratification for Treatment

Clinical Trial IDs

  • ORG STUDY ID: PASS-01
  • SECONDARY ID: CAPCR ID: 20-5105
  • NCT ID: NCT04469556

Conditions

  • Pancreatic Cancer Metastatic
  • Pancreatic Ductal Adenocarcinoma
  • Advanced Pancreatic Cancer

Interventions

DrugSynonymsArms
FolfirinoxFolinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, OxaliplatinModified Folfirinox
Gemcitabine/nab-paclitaxelGemcitabine/nab-Paclitaxel

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Modified FolfirinoxActive ComparatorModified 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.
  • Folfirinox
Gemcitabine/nab-PaclitaxelActive ComparatorGemcitabine/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.
  • Gemcitabine/nab-paclitaxel

Eligibility 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. -
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.
Time Frame:2-4 years
Safety Issue:
Description: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

Measure:ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA
Time Frame:2-4 years
Safety Issue:
Description:percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)
Measure:Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping
Time Frame:2-4 years
Safety Issue:
Description:
Measure:GATA6 as a biomarker of response to mFFX or GA
Time Frame:2-4 years
Safety Issue:
Description:
Measure:• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)
Time Frame:2-4 years
Safety Issue:
Description:
Measure:• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).
Time Frame:2-4 years
Safety Issue:
Description:
Measure:• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance
Time Frame:2-4 years
Safety Issue:
Description:
Measure:Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)
Time Frame:2-4 years
Safety Issue:
Description:
Measure:Cluster Tendency analysis using artificial neural networks and radiomic methods combined
Time Frame:2-4 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Health Network, Toronto

Last Updated

July 8, 2020