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MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

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ClinicalTrials.gov Identifier: NCT03611556
Recruitment Status : Recruiting
First Posted : August 2, 2018
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

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.

Condition or disease Intervention/treatment Phase
Carcinoma Metastatic Pancreatic Adenocarcinoma Biological: oleclumab Biological: durvalumab Combination Product: gemcitabine Combination Product: nab-paclitaxel Combination Product: oxaliplatin Combination Product: leucovorin Combination Product: 5-FU Phase 1 Phase 2

Detailed Description:
This is a Phase 1b/2, multicenter, open-label, dose-escalation, and dose-expansion study to assess the safety, preliminary antitumor activity, immunogenicity, and PK of oleclumab with or without durvalumab in combination with chemotherapy administered in subjects with metastatic PDAC. Subjects with previously untreated metastatic PDAC (1L metastatic PDAC) with be enrolled in Cohort A. Subjects with metastatic PDAC previously treated with gemcitabine-based chemotherapy (without exposure to 5-FU, capecitabine, or oxaliplatin, 2L metastatic PDAC) will be enrolled in Cohort B. The study consists of 2 parts, dose escalation (part 1) and dose expansion (Part 2).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 339 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 21, 2018
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A1
gemcitabine and nab-paclitaxel
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

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

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

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

Biological: 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
Other Name: MEDI4736

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

Active Comparator: Arm B1
mFOLFOX (oxaliplatin, leucovorin, 5-FU)
Combination Product: oxaliplatin
Subjects will receive oxaliplatin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

Combination Product: leucovorin
Subjects will receive leucovorin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

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
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

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

Combination Product: oxaliplatin
Subjects will receive oxaliplatin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

Combination Product: leucovorin
Subjects will receive leucovorin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

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
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

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

Biological: 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
Other Name: MEDI4736

Combination Product: oxaliplatin
Subjects will receive oxaliplatin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

Combination Product: leucovorin
Subjects will receive leucovorin (as part of modified FOLFOX) in combination with or without oleclumab and/or durvalumab until disease progression
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)

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
Other Name: Modified FOLFOX (oxaliplatin, leucovorin, and 5-FU)




Primary Outcome Measures :
  1. Incidence of Adverse Events as a measure of safety in dose escalation phase [ Time Frame: 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 ]
    The primary endpoint is safety as assessed by the presence of adverse events and serious adverse events

  2. Objective Response (OR) rate as a measure of antitumor activity in dose expansion phase [ Time Frame: 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 ]
    Best overall response of confirmed CR or confirmed PR according to RECIST version 1.1

  3. Incidence of clinically significant ECG abnormalities as a measure of safety in dose escalation phase [ Time Frame: 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 ]
    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

  4. Incidence of clinically significant laboratory values as a measure of safety in dose escalation phase [ Time Frame: 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 ]
    Assess the presence of clinically significant laboratory values from baseline


Secondary Outcome Measures :
  1. Incidence of Adverse Events as a measure of safety in dose expansion phase [ Time Frame: 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 ]
    Safety as assessed by the presence of adverse events and serious adverse events

  2. Objective Response (OR) rate as a measure of antitumor activity in dose escalation phase [ Time Frame: 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 ]
    Best overall response of confirmed CR or confirmed PR according to RECIST version 1.1 in Part 1 (dose escalation)

  3. Overall Survival (OS) [ Time Frame: From time randomization until death or study completion, about 2 years after the last subject dosed ]
    The time from randomization until death due to any cause in Part 2 (dose expansion)

  4. Progression-Free Survival (PFS) [ Time Frame: From start of treatment until death or study completion, about 2 years after the last subject dosed, which ever comes first ]
    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)

  5. Duration of Response (DoR) [ Time Frame: From time of informed consent through study completion, about 2 years after the last subject dosed ]
    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)

  6. Disease control (DC) [ Time Frame: During treatment through study completion, about 2 years after the last subject dosed ]
    CR, PR, or SD (if subjects maintain SD for ≥ 8 weeks [± 3 days]) in Part 1 (dose escalation) in Part 2 (dose expansion)

  7. Development of detectable anti-drug antibody (ADA) to oleclumab (MEDI9447) [ Time Frame: From start of treatment through 12 weeks post last dose of investigational product ]
    Immunogenicity of oleclumab

  8. Development of detectable anti-drug antibody(ADA) to durvalumab [ Time Frame: From start of treatment through 12 weeks post last dose of investigational product ]
    Immunogenicity of durvalumab

  9. Serum oleclumab (MEDI9447) concentration levels [ Time Frame: During treatment through 12 weeks post last dose of investigational product ]
    Pharmacokinetics of oleclumab

  10. Serum durvalumab concentration levels [ Time Frame: During treatment through 12 weeks post last dose of investigational product ]
    Pharmacokinetics of durvalumab

  11. Area under the curve (AUC) of selected chemo-therapies and /or their metabolites [ Time Frame: From start of treatment through the first 16 weeks of treatment ]
    Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites

  12. Maximun serum concentration (Cmax) of selected chemo-therapies and /or their metabolites [ Time Frame: From start of treatment through the first 16 weeks of treatment ]
    Pharmacokinetics of gemcitabine and nab paclitaxel and their metabolites

  13. Incidence of clinically significant ECG abnormalities as a measure of safety in dose expansion phase [ Time Frame: 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 ]
    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

  14. Incidence of clinically significant laboratory values as a measure of safety in dose expansion phase [ Time Frame: 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 ]
    Assess the presence of clinically significant laboratory values from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 101 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03611556


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, California
Research Site Recruiting
La Jolla, California, United States, 92093
United States, Colorado
Research Site Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Research Site Recruiting
Fort Myers, Florida, United States, 33901
United States, Georgia
Research Site Recruiting
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Research Site Recruiting
Boston, Massachusetts, United States, 02114
Research Site Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Research Site Recruiting
Ann Arbor, Michigan, United States, 48109
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14263
United States, North Carolina
Research Site Recruiting
Durham, North Carolina, United States, 27710
United States, Ohio
Research Site Recruiting
Cincinnati, Ohio, United States, 45219
Research Site Recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Research Site Recruiting
Philadelphia, Pennsylvania, United States, 19111
United States, Rhode Island
Research Site Not yet recruiting
Providence, Rhode Island, United States, 02903
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Research Site Recruiting
Dallas, Texas, United States, 75235
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Research Site Recruiting
Charlottesville, Virginia, United States, 22908
Research Site Recruiting
Fairfax, Virginia, United States, 22031
United States, Washington
Research Site Recruiting
Seattle, Washington, United States, 98109
United States, Wisconsin
Research Site Recruiting
Madison, Wisconsin, United States, 53705
Australia
Research Site Recruiting
Blacktown, Australia, 2148
Research Site Recruiting
Clayton, Australia, 3168
Research Site Recruiting
Heidelberg, Australia, 3084
Research Site Recruiting
St Leonards, Australia, 2065
Norway
Research Site Recruiting
Oslo, Norway, N-0379
Spain
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Fuenlabrada, Spain, 28942
Research Site Recruiting
Oviedo, Spain, 33011
Research Site Recruiting
Pamplona, Spain, 31008
Sponsors and Collaborators
MedImmune LLC
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Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT03611556    
Other Study ID Numbers: D6070C00005
D6070C00005 ( Other Grant/Funding Number: MedImmune, LLC )
First Posted: August 2, 2018    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 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
Access Criteria: 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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedImmune LLC:
MEDI9447
oleclumab
immunotherapy
pancreatic cancer
durvalumab
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Leucovorin
Gemcitabine
Paclitaxel
Oxaliplatin
Fluorouracil
Durvalumab
Levoleucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins