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A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)

This study is currently recruiting participants.
Verified August 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT03193190
First Posted: June 20, 2017
Last Update Posted: August 2, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
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).

Condition Intervention Phase
Pancreatic Adenocarcinoma Drug: Nab-Paclitaxel Drug: Gemcitabine Drug: Oxaliplatin Drug: Leucovorin Drug: Fluorouracil Drug: Atezolizumab Drug: Cobimetinib Drug: PEGPH20 Drug: BL-8040 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: 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 3-5 years) ]

Secondary Outcome Measures:
  • Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization up to the first occurrence of disease (up to approximately 3-5 years) ]
  • Overall Survival [ Time Frame: From randomization up to death from any cause (up to approximately 3-5 years) ]
  • Percentage of Participants who are Alive at Month 6 [ Time Frame: Month 6 ]
  • Duration of Response, as Determined by Investigator According to RECIST v1.1 [ Time Frame: 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 3-5 years) ]
  • Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion duration=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose(up to approximately 3-5 years) ]
  • Plasma Concentration of Cobimetinib [ Time Frame: Pre-dose (0 hr) and 2-4 hrs post-dose on Day 15 of Cycle 1 (cycle length=28 days) ]
  • Plasma Concentration of PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years)

  • Plasma Concentration of BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-5 years); 30 days after last dose (up to approximately 3-5 years)

  • Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-5 years); 30 days after last dose (up to approximately 3-5 years)


Estimated Enrollment: 185
Actual Study Start Date: July 5, 2017
Estimated Study Completion Date: April 4, 2020
Estimated Primary Completion Date: November 16, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chemotherapy (Gemcitabine + Nab-Paclitaxel or mFOLFOX6)
Participants who progressed on a prior fluoropyrimidine-based regimen will receive gemcitabine + nab-paclitaxel. Participants who progressed on a prior gemcitabine-based regimen will receive 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6). Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: Nab-Paclitaxel
Nab-Paclitaxel 125 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle.
Drug: Gemcitabine
Gemcitabine 1000 mg/m^2 IV infusion on Days 1, 8, and 15 of each 28-day cycle.
Drug: Oxaliplatin
Oxaliplatin 85 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle.
Drug: Leucovorin
Leucovorin 400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle.
Drug: Fluorouracil
Fluorouracil 400 mg/m^2 IV push on Days 1 and 15; and fluorouracil 2400 mg/m^2 IV continuous infusion over 46 hours on Days 1 and 2 and on Days 15 and 16 of each 28-day cycle.
Experimental: Atezolizumab + Cobimetinib
Participants will receive cobimetinib 60 milligrams (mg) once daily orally on Days 1-21 of each 28-day cycle; and atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28-day cycle.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Experimental: Atezolizumab + PEGPH20
Participants will receive PEGPH20 3 micrograms per kilogram (mcg/kg) IV infusion on Days 1, 8 and 15 of each 21-day cycle; and atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Drug: PEGPH20
PEGPH20 will be administered as per the schedule specified in the respective arm.
Experimental: Atezolizumab + BL-8040
Participants will receive BL-8040 1.25 milligrams per kilogram (mg/kg) subcutaneously (SC) on Days 1-5 of the first week, followed by combination treatment consisting of BL-8040 1.25 mg/kg SC three times a week on non-consecutive days and atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle. Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria.
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Drug: BL-8040
BL-8040 will be administered as per the schedule specified in the respective arm.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
  • Disease progression during or within 6 months after treatment with one line of 5-Fluorouracil (5-FU)- or gemcitabine-based chemotherapy in the metastatic setting
  • 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 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:

  • 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
  Contacts and Locations
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): NCT03193190


Contacts
Contact: Reference Study ID Number: WO39608 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, California
Helen Diller Fam Comp Can Ctr Not yet recruiting
San Francisco, California, United States, 94158
United States, Connecticut
Smilow Cancer Hospital at Yale New Haven Not yet recruiting
New Haven, Connecticut, United States, 06510
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Oregon
Oregon Health and Science University Not yet recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Hillman Cancer Center;Medical Oncology Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Cancer Center Recruiting
Germantown, Tennessee, United States, 38138
Germany
Charite - Campus Virchow-Klinikum Not yet recruiting
Berlin, Germany, 13353
Universitaetsklinikum Essen, Innere Klinik und Poliklinik fuer Tumorforschung Not yet recruiting
Essen, Germany, 45122
Korea, Republic of
Seoul National University Hospital Not yet recruiting
Seoul, Korea, Republic of, 03080
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 05505
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 06351
Spain
Clínica Universidad de Navarra Not yet recruiting
Pamplona, Navarra, Spain, 31008
Hospital Universitario Vall d'Hebron Not yet recruiting
Barcelona, Spain, 08035
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03193190     History of Changes
Other Study ID Numbers: WO39608
2016-004126-42 ( EudraCT Number )
First Submitted: June 9, 2017
First Posted: June 20, 2017
Last Update Posted: August 2, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Oxaliplatin
Atezolizumab
Albumin-Bound Paclitaxel
Fluorouracil
Antibodies, Monoclonal
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