A Study of Galunisertib (LY2157299) and Durvalumab (MEDI4736) in Participants With Metastatic Pancreatic Cancer

August 2, 2019 updated by: Eli Lilly and Company

A Phase 1b Dose-Escalation and Cohort-Expansion Study of the Safety, Tolerability, and Efficacy of a Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor (Galunisertib) Administered in Combination With the Anti-PD-L1 Antibody Durvalumab (MEDI4736) in Recurrent or Refractory Metastatic Pancreatic Cancer

The main purpose of this study is to evaluate the safety and efficacy of the study drug known as galunisertib administered in combination with the anti-programmed cell death-ligand 1 (PD-L1) antibody durvalumab in participants with refractory metastatic pancreatic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif Cedex, France, 94805
        • Gustave Roussy
  • Italy
      • Verona, Italy, 37134
        • Ospedale Policlinico Giambattista Rossi, Borgo Roma
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
    • Korea
      • Seoul, Korea, Korea, Republic of, 06351
        • Samsung Medical Center
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28050
        • Hospital Madrid Norte Sanchinarro
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Honor Health Research Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SCRI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must have histologic or cytologic confirmation of recurrent metastatic pancreatic adenocarcinoma based on standard diagnostic criteria. Recurrence must be documented by diagnostic biopsy.
  • Have measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
  • Have had disease progression, been refractory or intolerant to no more than 2 prior systemic regimens for locally advanced or metastatic pancreatic cancer. Participants who have received prior neoadjuvant therapy and who now have metastatic disease must have received 1 of the following for their metastatic disease: FOLFIRINOX, nanoparticle albumin-bound paclitaxel/gemcitabine, TS-1 (tegafur gimeracil oteracil potassium), irinotecan liposome injection/5-fluorouracil (5FU)/Leucovorin or single-agent gemcitabine prior to enrolment in this study.
  • Dose Escalation: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment) or to provide an available archival tumour sample if taken <3 years prior to enrolment if a new tumour biopsy is not feasible with an acceptable clinical risk.
  • Cohort Expansion: Able and willing to give valid written consent to undergo a new tumour biopsy (prior to study treatment). Able and willing to undergo a second tumour biopsy on treatment. Where possible, tumour lesions used for new biopsies should not be the same lesions used as RECIST target lesions, unless there are no other lesions suitable for biopsy. Archival samples may be required if there is inadequate tissue in the biopsy specimen.
  • Have adequate organ function.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Use approved contraceptive methods.

Exclusion Criteria:

  • Have moderate or severe cardiovascular disease:

    • Have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
    • Have documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments; for example, atrial fibrillation, bundle branch blocks, or as approved by the sponsors).
    • Have major abnormalities documented by ECHO with Doppler (for example, moderate or severe heart valve function defect including moderate or severe valve stenosis or regurgitation, left ventricular ejection fraction <50%, evaluation based on the institutional lower limit of normal, septal aneurysm or other heart aneurysm, any aneurysm of the major vessels or any condition that results in increased risk of aneurysm (eg, Marfan syndrome, patent foramen ovale [PFO]).
    • Have predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan syndrome, PFO, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computerized tomography [CT] scan with contrast or magnetic resonance imaging [MRI]).
  • Have evidence of interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity or active, noninfectious pneumonitis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Galunisertib + Durvalumab
(Dose Escalation and Cohort Expansion) Galunisertib administered orally in combination with durvalumab administered intravenously (IV).
Drug: Durvalumab
Administered IV
Other Names:
  • MEDI4736
Drug: Galunisertib
Administered orally
Other Names:
  • LY2157299

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Participants with Galunisertib in Combination with Durvalumab Dose-Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (28 Days)
Cycle 1 (28 Days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Galunisertib
Time Frame: Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
PK: Area Under the Curve (AUC) at Steady State of Galunisertib
Time Frame: Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
PK: Minimum Concentration (Cmin) of Durvalumab
Time Frame: Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
Predose Day 1 Cycle 1 through Predose Day 1 Cycle 7 (28 Day Cycles)
Number of Participants with Anti-Durvalumab Antibodies
Time Frame: Predose Day 1 Cycle 2 through Predose Day 1 Cycle 4 (28 Day Cycles)
Predose Day 1 Cycle 2 through Predose Day 1 Cycle 4 (28 Day Cycles)
Progression-free Survival (PFS)
Time Frame: Baseline to Objective Progressive Disease or Death (Estimated up to 18 Months)
Baseline to Objective Progressive Disease or Death (Estimated up to 18 Months)
Objective Response Rate (ORR): Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR)
Time Frame: Baseline to Objective Progressive Disease (Estimated up to 18 Months)
Baseline to Objective Progressive Disease (Estimated up to 18 Months)
Duration of Response (DoR)
Time Frame: Date of CR or PR to Date of Objective Progressive Disease or Death Due to Any Cause (Estimated up to 18 Months)
Date of CR or PR to Date of Objective Progressive Disease or Death Due to Any Cause (Estimated up to 18 Months)
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)
Time Frame: Baseline to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 18 Months)
Baseline to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Estimated up to 18 Months)
Time to Response
Time Frame: Baseline to Date of CR or PR (Estimated up to 4 Months)
Baseline to Date of CR or PR (Estimated up to 4 Months)
Overall Survival (OS)
Time Frame: Baseline to Date of Death from Any Cause (Estimated up to 30 Months)
Baseline to Date of Death from Any Cause (Estimated up to 30 Months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Collaborators

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 15, 2016

Primary Completion (Actual)

August 2, 2018

Study Completion (Actual)

April 17, 2019

Study Registration Dates

First Submitted

April 6, 2016

First Submitted That Met QC Criteria

April 6, 2016

First Posted (Estimate)

April 12, 2016

Study Record Updates

Last Update Posted (Actual)

August 5, 2019

Last Update Submitted That Met QC Criteria

August 2, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15784
  • H9H-MC-JBEG (Other Identifier: Eli Lilly and Company)
  • 2015-005295-26 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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