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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03611556
Ethics application status
Date submitted
18/05/2018
Date registered
2/08/2018
Date last updated
9/06/2020

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
Other interventions - oleclumab
Other interventions - durvalumab
Combination Product - gemcitabine
Combination Product - nab-paclitaxel
Combination Product - oxaliplatin
Combination Product - leucovorin
Combination Product - 5-FU

Active Comparator: Arm A1 - gemcitabine and nab-paclitaxel

Experimental: Arm A2 - oleclumab (MEDI9447), gemcitabine and nab-paclitaxel

Experimental: Arm A3 - oleclumab (MEDI9447), durvalumab (MEDI4736), and gemcitabine/nab-paclitaxel

Active Comparator: Arm B1 - mFOLFOX (oxaliplatin, leucovorin, 5-FU)

Experimental: Arm B2 - oleclumab (MEDI9447) and mFOLFOX (oxaliplatin, leucovorin, 5-FU)

Experimental: Arm B3 - oleclumab (MEDI9447), durvalumab (MEDI4736), and mFOLFOX (oxaliplatin, leucovorin, 5-FU)


Other interventions: oleclumab
Subjects will receive oleclumab with or without durvalumab and in combination with chemotherapy viz. gemcitabine and nab-paclitaxel or mFOLFOX (5FU, leucovorin and oxaliplatin) until disease progression

Other interventions: durvalumab
Subjects will receive durvalumab with oleclumab and in combination with chemotherapy viz. gemcitabine and nab-paclitaxel or mFOLFOX (5FU, leucovorin and oxaliplatin) until disease progression

Combination Product: gemcitabine
Subjects will receive gemcitabine in combination with nab-paclitaxel and with or without oleclumab and/or durvalumab until disease progression

Combination Product: nab-paclitaxel
Subjects will receive nab-paclitaxel in combination with gemcitabine and with or without oleclumab and/or durvalumab until disease progression

Combination Product: oxaliplatin
Subjects will receive oxaliplatin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression

Combination Product: leucovorin
Subjects will receive leucovorin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression

Combination Product: 5-FU
Subjects will receive a bolus of 5-FU followed by continuous 5-FU infusion (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Adverse Events as a measure of safety in dose escalation phase - The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events
Timepoint [1] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
Primary outcome [2] 0 0
Objective Response (OR) rate as a measure of antitumor activity in dose expansion phase - Best overall response of confirmed CR or confirmed PR according to RECIST version 1.1
Timepoint [2] 0 0
From start of treatment until documentation of disease progression or initiation of subsequent anticancer therapy or study completion, about 2 years after the last subject dosed, which ever comes first
Primary outcome [3] 0 0
Incidence of clinically significant ECG abnormalities as a measure of safety in dose escalation phase - 12 lead ECGs will be measured to identify clinical significant abnormalities including ECGs that demonstrate a QTcF value >500ms, 2 additional 12-lead ECGs should be obtained over a 30 minute time period to confirm prolongation based on the average QTcF value
Timepoint [3] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
Primary outcome [4] 0 0
Incidence of clinically significant laboratory values as a measure of safety in dose escalation phase - Assess the presence of clinically significant laboratory values from baseline
Timepoint [4] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
Secondary outcome [1] 0 0
Incidence of Adverse Events as a measure of safety in dose expansion phase - Safety as assessed by the presence of adverse events and serious adverse events
Timepoint [1] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
Secondary outcome [2] 0 0
Objective Response (OR) rate as a measure of antitumor activity in dose escalation phase - Best overall response of confirmed CR or confirmed PR according to RECIST version 1.1 in Part 1 (dose escalation)
Timepoint [2] 0 0
From start of treatment until documentation of disease progression or initiation of subsequent anticancer therapy or study completion, about 2 years after the last subject dosed, which ever comes first
Secondary outcome [3] 0 0
Overall Survival (OS) - The time from randomization until death due to any cause in Part 2 (dose expansion)
Timepoint [3] 0 0
From time randomization until death or study completion, about 2 years after the last subject dosed
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) - The time from randomization until the first documentation of disease progression or death due to any cause, whichever occurs first in Part 2 (dose expansion)
Timepoint [4] 0 0
From start of treatment until death or study completion, about 2 years after the last subject dosed, which ever comes first
Secondary outcome [5] 0 0
Duration of Response (DoR) - The duration from the first documentation of OR to the first documented disease progression or death due to any cause, whichever occurs first in Part 2 (dose expansion)
Timepoint [5] 0 0
From time of informed consent through study completion, about 2 years after the last subject dosed
Secondary outcome [6] 0 0
Disease control (DC) - CR, PR, or SD (if subjects maintain SD for = 8 weeks [± 3 days]) in Part 1 (dose escalation) in Part 2 (dose expansion)
Timepoint [6] 0 0
During treatment through study completion, about 2 years after the last subject dosed
Secondary outcome [7] 0 0
Development of detectable anti-drug antibody (ADA) to oleclumab (MEDI9447) - Immunogenicity of oleclumab
Timepoint [7] 0 0
From start of treatment through 12 weeks post last dose of investigational product
Secondary outcome [8] 0 0
Development of detectable anti-drug antibody(ADA) to durvalumab - Immunogenicity of durvalumab
Timepoint [8] 0 0
From start of treatment through 12 weeks post last dose of investigational product
Secondary outcome [9] 0 0
Serum oleclumab (MEDI9447) concentration levels - Pharmacokinetics of oleclumab
Timepoint [9] 0 0
During treatment through 12 weeks post last dose of investigational product
Secondary outcome [10] 0 0
Serum durvalumab concentration levels - Pharmacokinetics of durvalumab
Timepoint [10] 0 0
During treatment through 12 weeks post last dose of investigational product
Secondary outcome [11] 0 0
Area under the curve (AUC) of selected chemo-therapies and /or their metabolites - Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites
Timepoint [11] 0 0
From start of treatment through the first 16 weeks of treatment
Secondary outcome [12] 0 0
Maximun serum concentration (Cmax) of selected chemo-therapies and /or their metabolites - Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites
Timepoint [12] 0 0
From start of treatment through the first 16 weeks of treatment
Secondary outcome [13] 0 0
Incidence of clinically significant ECG abnormalities as a measure of safety in dose expansion phase - 12 lead ECGs will be measured to identify clinical significant abnormalities including ECGs that demonstrate a QTcF value >500ms, 2 additional 12-lead ECGs should be obtained over a 30 minute time period to confirm prolongation based on the average QTcF value
Timepoint [13] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year
Secondary outcome [14] 0 0
Incidence of clinically significant laboratory values as a measure of safety in dose expansion phase - Assess the presence of clinically significant laboratory values from baseline
Timepoint [14] 0 0
From time of informed consent through treatment period and including the follow-up period 12 weeks after last dose of investigational product, approximately 1 year

Eligibility
Key inclusion criteria
1. Age = 18

2. Written and signed informed consent must be obtained

3. ECOG Performance Status 0 or 1

4. Weight = 35 kg

5. Subjects must have histologically or cytologically, confirmed pancreatic
adenocarcinoma:

Cohort A: Subjects with previously untreated metastatic pancreatic adenocarcinoma (1st
line metastatic disease) not previously treated with systemic therapies.

Cohort B: Subjects with metastatic pancreatic adenocarcinoma previously treated with
gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, oxaliplatin)
2nd line metastatic disease

6. Subjects must have at least 1 measurable lesion according to RECIST v1.1

7. All subjects must consent to providing archival tumor specimens
Minimum age
18 Years
Maximum age
101 Years
Gender
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. Subjects with a history of venous thrombosis within the past 3 months

5. Subjects 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/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
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
Rhode Island
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
United States of America
State/province [16] 0 0
Wisconsin
Country [17] 0 0
Norway
State/province [17] 0 0
Oslo
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Fuenlabrada
Country [20] 0 0
Spain
State/province [20] 0 0
Oviedo
Country [21] 0 0
Spain
State/province [21] 0 0
Pamplona

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

Ethics approval
Ethics application status

Summary
Brief summary
The objective of this study is to evaluate the safety, tolerability, and antitumor activity
of oleclumab (MEDI9447) in combination with or without durvalumab plus chemotherapy in
subjects with metastatic pancreatic cancer.
Trial website
https://clinicaltrials.gov/show/NCT03611556
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

Summary results
Other publications