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Pancreatic Adenocarcinoma Signature Stratification for Treatment (PASS-01)

Primary Purpose

Pancreatic Cancer Metastatic, Pancreatic Ductal Adenocarcinoma, Advanced Pancreatic Cancer

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Folfirinox

Gemcitabine/nab-paclitaxel

About this trial

This is an interventional treatment trial for Pancreatic Cancer Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients must have a histological or radiological diagnosis of untreated metastatic PDAC at screening with histology subsequently confirmed prior to randomization.
Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma.
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.
Age ≥18 years.
Patient must have a tumor lesion that is amenable to a core needle biopsy.
Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen.
Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%).
Life expectancy of greater than 90 days, as judged by the investigator
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.
Within 14 days of the proposed randomization date, patients must have normal organ and marrow function

Exclusion Criteria:

Patients who have received prior systemic treatment for PDAC, including treatment in the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is permitted.
Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded.
Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures.
Patients with known brain metastases are excluded from participation in this clinical study.
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.
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.
Patients with a known germline mutation in BRCA, PALB2 or other homologous Recombination Repair Deficiency (HRD) genes.
Patients who are pregnant or breastfeeding.
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. -

Sites / Locations

Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterRecruiting
Dana Farber Cancer InstituteRecruiting
Northwell HealthRecruiting
Memorial Sloan Kettering Cancer CenterRecruiting
BC Cancer Agency VancouverRecruiting
Princess Margaret Cancer CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Modified Folfirinox

Gemcitabine/nab-Paclitaxel

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.

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

ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA

percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)

Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping

GATA6 as a biomarker of response to mFFX or GA

• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)

• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).

• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance

Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)

Cluster Tendency analysis using artificial neural networks and radiomic methods combined

Full Information

NCT ID

NCT04469556

First Posted

June 26, 2020

Last Updated

April 12, 2022

Sponsor

University Health Network, Toronto

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

1. Study Identification

Unique Protocol Identification Number

NCT04469556

Brief Title

Pancreatic Adenocarcinoma Signature Stratification for Treatment

Acronym

PASS-01

Official Title

Pancreatic Adenocarcinoma Signature Stratification for Treatment

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

October 14, 2020 (Actual)

Primary Completion Date

September 2022 (Anticipated)

Study Completion Date

September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Cancer Metastatic, Pancreatic Ductal Adenocarcinoma, Advanced Pancreatic Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

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)

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Modified Folfirinox

Arm Type

Active Comparator

Arm Description

Arm Title

Gemcitabine/nab-Paclitaxel

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Folfirinox

Other Intervention Name(s)

Folinic Acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin

Intervention Description

Chemotherapy

Intervention Type

Drug

Intervention Name(s)

Gemcitabine/nab-paclitaxel

Intervention Description

Chemotherapy

Primary Outcome Measure Information:

Title

Progression free survival(PFS) in mFFX and GA arms pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II trial.

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

Time Frame

2-4 years

Secondary Outcome Measure Information:

Title

ORR by RECIST 1.1 and duration of response in patients receiving mFFX or GA

Description

percentage of patient's measurable disease who have achieved either complete response (CR) or partial response (PR)

Time Frame

2-4 years

Title

Overall survival (OS) associated with mFFX or GA profiles, signatures and pharmacotyping

Time Frame

2-4 years

Title

GATA6 as a biomarker of response to mFFX or GA

Time Frame

2-4 years

Title

• Concordance between organoid transcriptomic profiles (RNAseq) and patient transcriptomic profiles (descriptive statistics)

Time Frame

2-4 years

Title

• Concordance between chemotherapy sensitivity signature predictions and response to first line treatment (descriptive statistics).

Time Frame

2-4 years

Title

• Correlation of individual tumour cytokeratins (eg. CK5 and CK17 expression) with chemotherapy response and resistance

Time Frame

2-4 years

Title

Cell free circulating tumor (ct) DNA analysis (including KRAS mutational status)

Time Frame

2-4 years

Title

Cluster Tendency analysis using artificial neural networks and radiomic methods combined

Time Frame

2-4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients must have a histological or radiological diagnosis of untreated metastatic PDAC at screening with histology subsequently confirmed prior to randomization. Eligible histologic variants include adenocarcinoma or variants to include mucinous adenocarcinoma or adenosquamous carcinoma. 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. Age ≥18 years. Patient must have a tumor lesion that is amenable to a core needle biopsy. Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen. Eastern Cooperative Group (ECOG) performance status 0-1. (Karnofsky ≥70%). Life expectancy of greater than 90 days, as judged by the investigator 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. Within 14 days of the proposed randomization date, patients must have normal organ and marrow function Exclusion Criteria: Patients who have received prior systemic treatment for PDAC, including treatment in the neoadjuvant or adjuvant setting. Prior surgery or palliative radiation is permitted. Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded. Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures. Patients with known brain metastases are excluded from participation in this clinical study. 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. 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. Patients with a known germline mutation in BRCA, PALB2 or other homologous Recombination Repair Deficiency (HRD) genes. Patients who are pregnant or breastfeeding. 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. -

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Anna J Dodd

Phone

416-946-2399

anna.dodd@uhn.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elizabeth Jaffee, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Jennifer J Knox, MD

Organizational Affiliation

University Health Network, Toronto

Official's Role

Study Chair

Facility Information:

Facility Name

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel Laheru, MD

Facility Name

Dana Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kimberley Perez, MD

Facility Name

Northwell Health

City

New Hyde Park

State/Province

New York

ZIP/Postal Code

11042

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Daniel King, MD

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kenneth Yu, MD

Facility Name

BC Cancer Agency Vancouver

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V5Z 1L8

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Suilee Quach

Phone

604-877-6000

Ext

674826

Facility Name

Princess Margaret Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2N9

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anna Dodd

Phone

647-539-6498

anna.dodd@uhn.ca

12. IPD Sharing Statement

Plan to Share IPD

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