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MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03611556
Recruitment Status : Active, not recruiting
First Posted : August 2, 2018
Last Update Posted : March 21, 2022
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE May 18, 2018
First Posted Date  ICMJE August 2, 2018
Last Update Posted Date March 21, 2022
Actual Study Start Date  ICMJE June 21, 2018
Estimated Primary Completion Date December 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
  • 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
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2018)
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
  • 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
  • Serum oleclumab (MEDI9447) concentration levels [ Time Frame: During treatment through 12 weeks post last dose of investigational product ]
    Pharmacokinetics of oleclumab
  • Serum durvalumab concentration levels [ Time Frame: During treatment through 12 weeks post last dose of investigational product ]
    Pharmacokinetics of durvalumab
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MEDI9447(Oleclumab) Pancreatic Chemotherapy Combination Study.
Official Title  ICMJE 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
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.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma
  • Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • 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
  • 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)
Study Arms  ICMJE
  • Active Comparator: Arm A1
    gemcitabine and nab-paclitaxel
    Interventions:
    • Combination Product: gemcitabine
    • Combination Product: nab-paclitaxel
  • Experimental: Arm A2
    oleclumab (MEDI9447), gemcitabine and nab-paclitaxel
    Interventions:
    • Biological: oleclumab
    • Combination Product: gemcitabine
    • Combination Product: nab-paclitaxel
  • Experimental: Arm A3
    oleclumab (MEDI9447), durvalumab (MEDI4736), and gemcitabine/nab-paclitaxel
    Interventions:
    • Biological: oleclumab
    • Biological: durvalumab
    • Combination Product: gemcitabine
    • Combination Product: nab-paclitaxel
  • Active Comparator: Arm B1
    mFOLFOX (oxaliplatin, leucovorin, 5-FU)
    Interventions:
    • Combination Product: oxaliplatin
    • Combination Product: leucovorin
    • Combination Product: 5-FU
  • Experimental: Arm B2
    oleclumab (MEDI9447) and mFOLFOX (oxaliplatin, leucovorin, 5-FU)
    Interventions:
    • Biological: oleclumab
    • Combination Product: oxaliplatin
    • Combination Product: leucovorin
    • Combination Product: 5-FU
  • Experimental: Arm B3
    oleclumab (MEDI9447), durvalumab (MEDI4736), and mFOLFOX (oxaliplatin, leucovorin, 5-FU)
    Interventions:
    • Biological: oleclumab
    • Biological: durvalumab
    • Combination Product: oxaliplatin
    • Combination Product: leucovorin
    • Combination Product: 5-FU
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 18, 2022)
212
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2018)
204
Estimated Study Completion Date  ICMJE December 15, 2022
Estimated Primary Completion Date December 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 101 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Norway,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03611556
Other Study ID Numbers  ICMJE D6070C00005
D6070C00005 ( Other Grant/Funding Number: MedImmune, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MedImmune LLC
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP