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Durvalumab and Oleclumab in Resectable PDAC (DORA)

Primary Purpose

Pancreatic Ductal Adenocarcinoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Durvalumab
Oleclumab
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

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

Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Weight ≥ 35 kg Have a life expectancy ≥ 12 weeks Have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC). Upfront resectable PDAC Have adequate organ and marrow function required for the study Baseline images taken prior to treatment must undergo central review Participants must agree to use study approved methods to prevent pregnancy for study required period Exclusion Criteria: Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment Prior receipt of any immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1 including durvalumab antibodies and agents targeting CD73, CD39, or adenosine receptors, excluding therapeutic anticancer vaccines. Concurrent enrolment in another therapeutic clinical study. Enrolment in observational studies will be allowed. Have a history of Grade 3 or greater thromboembolic events in the prior 3 months or thromboembolic event of any grade with ongoing symptoms. Have prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment with the following exceptions Vitiligo or alopecia Hypothyroidism not requiring systemic treatment or stable on hormone replacement Psoriasis not requiring systemic treatment Any chronic skin condition that does not require systemic therapy Have known active hepatitis infection. Participants with a past or resolved Hepatitis B (HBV) infection are eligible. Participants positive for Hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection Other invasive malignancy within 5 years. Known allergy or hypersensitivity to investigational product formulations. Active grade 3 or greater edema Uncontrolled intercurrent illness Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment with the following exceptions: Intranasal, topical, inhaled corticosteroids or local steroid injections Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent Steroids as premedication for hypersensitivity reaction Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery. Local are allowed, without needing to wait for the 28 day recovery period. Are pregnant, lactating, or intend to become pregnant during their participation in the study Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results

Sites / Locations

  • Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Durvalumab and Oleclumab

Arm Description

Durvalumab, 1500 mg x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to surgical resection.

Outcomes

Primary Outcome Measures

Percent change in CD8+ cell infiltration

Secondary Outcome Measures

Percent change in CD3 cell population in tumour tissue
Percent change in CD3 cell population in blood
Percent change in CD45RA cell population in tumour tissue
Percent change in CD45RA cell population in blood
Percent change in RO T cell population in tumour tissue
Percent change in RO T cell population in blood
Percent change in M1 vs M2 macrophage population in tumour tissue
Percent change in M1 vs M2 macrophage population in blood

Full Information

First Posted
September 22, 2023
Last Updated
September 22, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT06060405
Brief Title
Durvalumab and Oleclumab in Resectable PDAC
Acronym
DORA
Official Title
Durvalumab and Oleclumab in Resectable PDAC: A Window of Opportunity Study (DORA Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 30, 2023 (Anticipated)
Primary Completion Date
October 30, 2026 (Anticipated)
Study Completion Date
October 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multi-site Canadian, window of opportunity study to evaluate the immune activity of durvalumab and oleclumab in resectable pancreatic ductal adenocarcinoma (PDAC) when given prior to surgery.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab and Oleclumab
Arm Type
Experimental
Arm Description
Durvalumab, 1500 mg x 1 dose and oleclumab 3000 mg x 2 doses every 2 weeks prior to surgical resection.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
IMFINZI
Intervention Description
Durvalumab is a monoclonal antibody that blocks the interaction of PD-L1 with PD-1 on immune cells.
Intervention Type
Drug
Intervention Name(s)
Oleclumab
Other Intervention Name(s)
MEDI9447
Intervention Description
Oleclumab is a monoclonal antibody that binds to and inhibits the activity of CD73.
Primary Outcome Measure Information:
Title
Percent change in CD8+ cell infiltration
Time Frame
Baseline biopsy to surgical resection (35 days)
Secondary Outcome Measure Information:
Title
Percent change in CD3 cell population in tumour tissue
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in CD3 cell population in blood
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in CD45RA cell population in tumour tissue
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in CD45RA cell population in blood
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in RO T cell population in tumour tissue
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in RO T cell population in blood
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in M1 vs M2 macrophage population in tumour tissue
Time Frame
Baseline biopsy to surgical resection (35 days)
Title
Percent change in M1 vs M2 macrophage population in blood
Time Frame
Baseline biopsy to surgical resection (35 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Weight ≥ 35 kg Have a life expectancy ≥ 12 weeks Have histologically or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC). Upfront resectable PDAC Have adequate organ and marrow function required for the study Baseline images taken prior to treatment must undergo central review Participants must agree to use study approved methods to prevent pregnancy for study required period Exclusion Criteria: Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment Prior receipt of any immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1 including durvalumab antibodies and agents targeting CD73, CD39, or adenosine receptors, excluding therapeutic anticancer vaccines. Concurrent enrolment in another therapeutic clinical study. Enrolment in observational studies will be allowed. Have a history of Grade 3 or greater thromboembolic events in the prior 3 months or thromboembolic event of any grade with ongoing symptoms. Have prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment with the following exceptions Vitiligo or alopecia Hypothyroidism not requiring systemic treatment or stable on hormone replacement Psoriasis not requiring systemic treatment Any chronic skin condition that does not require systemic therapy Have known active hepatitis infection. Participants with a past or resolved Hepatitis B (HBV) infection are eligible. Participants positive for Hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection Other invasive malignancy within 5 years. Known allergy or hypersensitivity to investigational product formulations. Active grade 3 or greater edema Uncontrolled intercurrent illness Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment with the following exceptions: Intranasal, topical, inhaled corticosteroids or local steroid injections Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent Steroids as premedication for hypersensitivity reaction Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery. Local are allowed, without needing to wait for the 28 day recovery period. Are pregnant, lactating, or intend to become pregnant during their participation in the study Any condition that, in the opinion of the investigator, would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Malcolm Moore, MD
Phone
416-946-2263
Email
malcolm.moore@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm Moore, MD
Organizational Affiliation
Princess Margaret Cancer Centre/University Health Network
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Malcolm Moore, MD
First Name & Middle Initial & Last Name & Degree
Malcolm Moore, MD

12. IPD Sharing Statement

Learn more about this trial

Durvalumab and Oleclumab in Resectable PDAC

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