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

Metastatic Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02734160
• Other study ID #: 15784
• Secondary ID: H9H-MC-JBEG2015-
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2016
• Est. completion date: April 17, 2019

Study information

• Verified date: August 1, 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: April 17, 2019
• Est. primary completion date: August 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Galunisertib
Administered orally
• Durvalumab
Administered IV

Locations

Country	Name	City	State
France	Gustave Roussy	Villejuif Cedex
Italy	Ospedale Policlinico Giambattista Rossi, Borgo Roma	Verona
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Madrid Norte Sanchinarro	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Honor Health Research Institute	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	AstraZeneca

Countries where clinical trial is conducted

United States,  France,  Italy,  Korea, Republic of,  Spain, 

Outcome

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

External Links

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