Clinical trial NCT03193190: A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Adenocarcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-06-20
Enrollment: 341
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of patients who have received no prior systemic therapy for metastatic PDAC, and Cohort 2 will consist of patients who have received one line of prior systemic therapy for PDAC. In each cohort, eligible patients will be assigned to one of several treatment arms.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
* For patients in Cohort 1: no prior systemic treatment for PDAC
* For patients in Cohort 2: disease progression during administration of either 5-FU- or gemcitabine-based first-line chemotherapy
* Life expectancy greater than or equal to 3 months
* Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing
* Measurable disease (at least one target lesion) according to RECIST v1.1
* Adequate hematologic and end-organ function test results
* Tumor accessible for biopsy
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Exclusion Criteria:

* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage procedure (i.e., more than one time per month)
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
* History of leptomeningeal disease
* Active or history of autoimmune disease or immune deficiency
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Positive human immunodeficiency (HIV) test at screening or at any time prior to screening
* Active hepatitis B or C virus infection or active tuberculosis
* Severe infection within 4 weeks prior to initiation of study treatment
* Prior allogeneic stem cell or solid organ transplantation
* History of malignancy other than pancreatic carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death

Primary outcomes:
measure: Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
timeFrame: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 7-9 years)
Secondary outcomes:
measure: Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1
timeFrame: From randomization up to the first occurrence of disease (up to approximately 7-9 years)
measure: Overall Survival
timeFrame: From randomization up to death from any cause (up to approximately 7-9 years)
measure: Percentage of Participants who are Alive at Month 6
timeFrame: Month 6
measure: Duration of Response, as Determined by Investigator According to RECIST v1.1
timeFrame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 7-9 years)
measure: Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1
timeFrame: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Helen Diller Fam Comp Can Ctr
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center, Georgetown University
state: District of Columbia
city: Chicago
country: United States
facility: Uni of Chicago Medical Center
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Morristown
country: United States
facility: MorristownMedicalCenter
state: New Jersey
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d Hebron
city: Madrid
country: Spain
facility: Hosp. G. U Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: