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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03611556




Registration number
NCT03611556
Ethics application status
Date submitted
18/05/2018
Date registered
2/08/2018

Titles & IDs
Public title
MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.
Scientific title
A Phase 1b/2 Study to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of Oleclumab (MEDI9447) With or Without Durvalumab in Combination With Chemotherapy in Subjects With Metastatic Pancreatic Ductal Adenocarcinoma
Secondary ID [1] 0 0
D6070C00005
Secondary ID [2] 0 0
D6070C00005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma 0 0
Metastatic Pancreatic Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oleclumab
Treatment: Drugs - Durvalumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Folinic acid
Treatment: Drugs - 5-FU

Experimental: Dose-escalation, Oleclumab 1500 mg + Durvalumab + Gemcitabine + nab-paclitaxel - Participants with 1L metastatic disease will receive intravenous (IV) infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then every 4 weeks (Q4W) in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Experimental: Dose-escalation, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel - Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Experimental: Dose-escalation, Oleclumab 1500 mg + Durvalumab + mFOLFOX - Participants with 2L metastatic disease will receive IV infusions of oleclumab 1500 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Experimental: Dose-escalation, Oleclumab 3000 mg + Durvalumab + mFOLFOX - Participants with 2L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of mFOLFOX (oxaliplatin 85 mg/m\^2 IV; folinic acid 400 mg/m\^2 IV; 5-FU 400 mg/m\^2 IV bolus followed by 2400 mg/m\^2 continuous IV infusion over 46 to 48 hours) on Days 1 and 15 and then repeated on a Q4W schedule, until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Active comparator: Dose-expansion, Gemcitabine + nab-paclitaxel - Participants with 1L metastatic disease will receive IV infusions of chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Experimental: Dose-expansion, Oleclumab 3000 mg + Gemcitabine + nab-paclitaxel - Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.

Experimental: Dose-expansion, Oleclumab 3000 mg + Durvalumab + Gemcitabine + nab-paclitaxel - Participants with 1L metastatic disease will receive IV infusions of oleclumab 3000 mg every 2 weeks for 4 doses, then Q4W in combination with durvalumab 1500 mg Q4W plus chemotherapy of gemcitabine 1000 mg/m\^2 and nab-paclitaxel 125 mg/m\^2, both on Days 1, 8, and 15 and then repeated on Q4W schedule until disease progression, intolerable toxicity, withdrawal of participant consent, or another discontinuation criterion is met.


Treatment: Drugs: Oleclumab
Participants will receive IV infusion of oleclumab as stated in arm description.

Treatment: Drugs: Durvalumab
Participants will receive IV infusion of durvalumab as stated in arm description.

Treatment: Drugs: Gemcitabine
Participants will receive IV infusion of gemcitabine as stated in arm description.

Treatment: Drugs: Nab-paclitaxel
Participants will receive IV infusion of nab-paclitaxel as stated in arm description.

Treatment: Drugs: Oxaliplatin
Participants will receive IV infusion of oxaliplatin as stated in arm description.

Treatment: Drugs: Folinic acid
Participants will receive IV infusion of folinic acid as stated in arm description.

Treatment: Drugs: 5-FU
Participants will receive IV infusion of 5-FU as stated in arm description.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose Escalation Phase
Timepoint [1] 0 0
Day 1 through 65.7 weeks (maximum observed duration)
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicities (DLTs) in Dose Escalation Phase
Timepoint [2] 0 0
From Day 1 to 28 days after the first dose of study drugs
Primary outcome [3] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Escalation Phase
Timepoint [3] 0 0
Day 1 through 65.7 weeks (maximum observed duration)
Primary outcome [4] 0 0
Number of Participants With Abnormal Electrocardiogram (ECG) Parameters Reported as TEAEs in Dose Escalation Phase
Timepoint [4] 0 0
Day 1 through 65.7 weeks (maximum observed duration)
Primary outcome [5] 0 0
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Escalation Phase
Timepoint [5] 0 0
Day 1 through 65.7 weeks (maximum observed duration)
Primary outcome [6] 0 0
Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose Expansion Phase
Timepoint [6] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [1] 0 0
Number of Participants With TEAEs and TESAEs in Dose Expansion Phase
Timepoint [1] 0 0
Day 1 through 172.1 weeks (maximum observed duration)
Secondary outcome [2] 0 0
Number of Participants With Abnormal Vital Signs Reported as TEAEs in Dose Expansion Phase
Timepoint [2] 0 0
Day 1 through 172.1 weeks (maximum observed duration)
Secondary outcome [3] 0 0
Number of Participants With Abnormal ECG Parameters Reported as TEAEs in Dose Expansion Phase
Timepoint [3] 0 0
Day 1 through 172.1 weeks (maximum observed duration)
Secondary outcome [4] 0 0
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose Expansion Phase
Timepoint [4] 0 0
Day 1 through 172.1 weeks (maximum observed duration)
Secondary outcome [5] 0 0
Percentage of Participants With OR According to RECIST v1.1 in Dose Escalation Phase
Timepoint [5] 0 0
Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
Secondary outcome [6] 0 0
Percentage of Participants With Disease Control (DC) According to RECIST v1.1 in Dose Escalation Phase
Timepoint [6] 0 0
Baseline (Days -28 to -1) through 24.5 months (maximum observed duration)
Secondary outcome [7] 0 0
Number of Participants With Overall Survival Events in Dose Expansion Phase
Timepoint [7] 0 0
Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Secondary outcome [8] 0 0
Overall Survival in Dose Expansion Phase
Timepoint [8] 0 0
Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Secondary outcome [9] 0 0
Number of Participants With Progression-free Survival Events According to RECIST v1.1 in Dose Expansion Phase
Timepoint [9] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [10] 0 0
Progression-free Survival According to RECIST v1.1 in Dose Expansion Phase
Timepoint [10] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [11] 0 0
Duration of Response (DoR) According to RECIST v1.1 in Dose Expansion Phase
Timepoint [11] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [12] 0 0
Percentage of Participants With DC According to RECIST v1.1 in Dose Expansion Phase
Timepoint [12] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [13] 0 0
Percentage of Participants With OR According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
Timepoint [13] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [14] 0 0
Number of Participants With Overall Survival Events by CD73 Expression at Baseline in Dose Expansion Phase
Timepoint [14] 0 0
Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Secondary outcome [15] 0 0
Overall Survival by CD73 Expression at Baseline in Dose Expansion Phase
Timepoint [15] 0 0
Baseline (Days -28 to -1) through 38.7 months (maximum observed duration)
Secondary outcome [16] 0 0
Number of Participants With Progression-free Survival Events According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
Timepoint [16] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [17] 0 0
Progression-free Survival According to RECIST v1.1 by CD73 Expression at Baseline in Dose Expansion Phase
Timepoint [17] 0 0
Baseline (Days -28 to -1) through 36.1 months (maximum observed duration)
Secondary outcome [18] 0 0
Number of Participants With Positive Anti-drug Antibodies (ADA) to Oleclumab
Timepoint [18] 0 0
Day 1 through 172.1 weeks (Pre-dose on Cycle [C] 1 Day [D] 1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of oleclumab)
Secondary outcome [19] 0 0
Number of Participants With Positive ADA to Durvalumab
Timepoint [19] 0 0
Day 1 through 128 weeks (Pre-dose on C1D1, C2D1, C3D1, Day 1 of every 3 cycles starting with C5, through 12 weeks post last dose of durvalumab)
Secondary outcome [20] 0 0
Serum Concentrations of Oleclumab
Timepoint [20] 0 0
Ten minutes (mins) (± 5 mins) post end of infusion (EOI), approximately 1 hour (+ 15 mins) after start of infusion on C1D1, C3D1, and C5D1; and pre-dose on C3D1 and C5D1
Secondary outcome [21] 0 0
Serum Concentrations of Durvalumab
Timepoint [21] 0 0
Ten mins (± 5 mins) post EOI, approximately 1 hour (+ 15 mins) after start of infusion on C1D1 and C5D1; and pre-dose on C2D1 and C5D1
Secondary outcome [22] 0 0
Plasma Concentrations of Gemcitabine and Metabolite 2',2'-Difluorodeoxyuridine (dFdU)
Timepoint [22] 0 0
Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1
Secondary outcome [23] 0 0
Plasma Concentrations of Nab-paclitaxel
Timepoint [23] 0 0
Ten mins (± 5 mins) post EOI, approximately 30-40 mins after start of infusion on C1D1 and C4D1; and pre-dose on C4D1

Eligibility
Key inclusion criteria
1. Age >= 18
2. Written and signed informed consent must be obtained
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
4. Weight >= 35 kg
5. Participants must have histologically or cytologically, confirmed pancreatic adenocarcinoma:

Cohort A: Participants with previously untreated metastatic pancreatic adenocarcinoma (1L metastatic disease) not previously treated with systemic therapies Cohort B: Participants with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin) 2L metastatic disease
6. Participants must have at least 1 measurable lesion according to RECIST v1.1
7. All Participants must consent to providing archival tumor specimens.
Minimum age
18 Years
Maximum age
101 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.
2. Prior receipt of any immune-related therapy
3. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed.
4. Participants with a history of venous thrombosis within the past 3 months
5. Participants with prior history of myocardial infarction, transient ischemic attack, or stroke in the last 3 months prior to start of treatment
6. Active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment
7. Other invasive malignancy within 2 years
8. Any history of leptomeningeal disease or cord compression
9. Current or prior use of immunosuppressive medication within 14 days prior to the first dose.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Blacktown
Recruitment hospital [2] 0 0
Research Site - Clayton
Recruitment hospital [3] 0 0
Research Site - Heidelberg
Recruitment hospital [4] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Virginia
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Norway
State/province [16] 0 0
Oslo
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Fuenlabrada
Country [19] 0 0
Spain
State/province [19] 0 0
Oviedo
Country [20] 0 0
Spain
State/province [20] 0 0
Pamplona

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.