Evaluation of Efficacy and Safety of Neoadjuvant Treatment With Pamrevlumab in Combination With Chemotherapy (Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX) in Participants With Locally Advanced, Unresectable Pancreatic Cancer (LAPIS)

October 15, 2024 updated by: FibroGen

A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in Combination With Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer

This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX in the treatment of participants with locally advanced, unresectable pancreatic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Participants will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with either G/NP or FOLFIRINOX, placebo with G/NP or FOLFIRINOX.

Each participant may receive up to 6 cycles of treatment (each treatment cycle is 28 days). Tumor tissue will be collected during resection to determine surgical outcome and for biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9, and NCCN® guidelines.

All participants randomized will have a safety follow-up visit approximately 28 days after the last dose of study treatment and a final safety follow-up phone call at approximately 60 days after the last dose.

Participants who complete study treatment will be evaluated for surgical exploration for possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose (allowing for a wash-out period from treatment) and only after receipt of the recommendation from the central review board with regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose. Participants who undergo surgery will be evaluated for surgical complications for at least an additional 90 days following discharge from surgery.

Participants who are ineligible for surgical exploration (i.e. participants who did not complete study treatment or do not meet any of the protocol defined criteria or had a contraindication to surgery) will continue in the Follow-up period and receive treatment as per standard of care (SOC) for each institution.

All participants will be followed for disease progression (if not previously detected) or recurrence following resection (local progression or metastatic disease). Participants will also be followed for any additional anti-cancer therapy received for their pancreatic cancer. All participants will be followed for survival (until death) or until the last participant to complete treatment reaches 18 months post-treatment.

Study Type

Interventional

Enrollment (Actual)

284

Phase

  • Phase 3

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

  • Austria
      • Wels, Austria, 4600
        • Klinikum Wels-Grieskirchen GmbH
      • Wien, Austria, 1090
        • Medizinische Universität Wien
  • Belgium
      • Brussels, Belgium, 1070
        • CUB Hôpital Erasme
  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre/University Health Network
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Center
  • China
      • Chengdu, China
        • West China Hospital of Sichuan University
      • Nanjing, China
        • Jiangsu Province Hospital
      • Shanghai, China
        • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Shanghai, China
        • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Beijing
      • Dongcheng, Beijing, China, 100010
        • Peking Union Medical College Hospital
    • Hubei
      • Wuhan, Hubei, China
        • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
    • Shaanxi
      • Xi'an, Shaanxi, China
        • The First Affiliated Hospital of Xi'an Jiaotong University
    • Shanghai
      • Jing'an, Shanghai, China, 200040
        • Huashan Hospital Affiliated with Fudan University
  • France
      • Besançon Cedex, France, 25030
        • CHRU Jean Minjoz
      • Clermont Ferrand, France, 63003
        • CHU Estaing
      • Clichy, France, 92118
        • Hôpital Beaujon
      • Dijon, France, 21079
        • Centre Georges-François Leclerc
      • La Tronche, France, 38700
        • CHU Grenoble Alpes
      • Lyon, France, 69373
        • Centre Leon Berard
      • Lyon, France, 69437
        • Hôpital Edouard Herriot
      • Paris, France, 750013
        • Groupe Hospitalier Pitié Salpêtrière
      • Pessac, France, 33604
        • Haut-Lévêque
      • Saint Herblain Cedex, France, 44805
        • INSTITUT DE CANCEROLOGIE DE L'OUEST Pays de Loire
  • Germany
      • Berlin, Germany, 10117
        • Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie
      • Dresden, Germany, 01307
        • Technische Universität Dresden, Medizinische Klinik und Poliklinik I
      • München, Germany, 81675
        • Klinikum rechts der Isar der Technischen Universität München
      • München, Germany, 81377
        • Klinikum der Universität München, Medizinische Klinik und Poliklinik III
  • Israel
      • Be'er Ya'aqov, Israel, 7030000
        • Shamir Medical center Asaf Harofeh
      • Jerusalem, Israel, 9112001
        • Hadassah University Hospital Ein Kerem
      • Kfar Saba, Israel, 4428164
        • Meir Medical Center
      • Petach Tikva, Israel, 4941492
        • Rabin Medical Center
  • Italy
      • Meldola, Italy, 47014
        • Instituto Scientifico Romagnolog per lo Studio e la Cura dei Tumori
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Milano, Italy, 20141
        • Istituto Europeo di Oncologia
      • Milano, Italy, 20162
        • Grande Ospedale Metropolitano Niguarda, Oncologia Medica Falck
      • Napoli, Italy, 80131
        • AOU Federico II
      • Rozzano, Italy, 20089
        • Istituto Clinico Humanitas
      • Verona, Italy, 37134
        • CRC di Verona
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 06591
        • The Catholic University of Korea, Seoul St. Mary's Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
    • Geyonggi-do
      • Seongnam-si, Geyonggi-do, Korea, Republic of, 13620
        • Seoul national University Budang hospital
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
        • National Cancer Center
    • Jeollanam-do
      • Hwasun, Jeollanam-do, Korea, Republic of, 58128
        • Chonnam National University Hwasun Hospital
  • Spain
      • Barcelona, Spain, 8041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08035
        • Hospital Universitaro Vall D'Hebron
      • Girona, Spain, 17007
        • Institut Catalá d'Oncologia (ICO Girona). Hospital Dr. Josep Trueta
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36312
        • Álvaro Cunqueiro Hospital
  • United Kingdom
      • London, United Kingdom, NW1 2PG
        • University College London Hospitals Nhs Foundation Trust
      • London, United Kingdom, W2 1NY
        • Imperial College Healthcare NHS Trust
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • St. Joseph's Hospital and Medical Cancer Center
    • California
      • La Jolla, California, United States, 92037
        • UC San Diego Moores Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale New Haven Hospital
    • Illinois
      • Elmhurst, Illinois, United States, 60126
        • Elmhurst Memorial Hospital - Nancy W. Knowles Cancer Center
      • Naperville, Illinois, United States, 60540
        • Edward Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 48202
        • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Hospital
    • Kentucky
      • Louisville, Kentucky, United States, 40217
        • Norton Cancer Institute, Audubon Hospital Campus
    • Maine
      • South Portland, Maine, United States, 04106
        • Maine Health Cancer Care
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68105
        • University of Nebraska Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • New Mexico Cancer Care Alliance
    • New York
      • New York, New York, United States, 11735
        • NYU Langone Health
      • Stony Brook, New York, United States, 11794
        • Stony Brook University
      • Syracuse, New York, United States, 13210
        • Suny Upstate Medical University
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Medical Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • West Reading, Pennsylvania, United States, 19611
        • Reading Hospital McGlinn Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine
      • Temple, Texas, United States, 76508
        • Baylor Scott & White Medical Center
      • The Woodlands, Texas, United States, 77380
        • Renovatio Clinic
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Seattle, Washington, United States, 98101
        • Virginia Mason Medical Center
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University

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

Description

Inclusion Criteria:

  1. Understand and sign informed consent; be willing to comply with study procedures, including surgery
  2. Age ≥ 18 years
  3. Be a male, or non-pregnant and non-lactating female
  4. Negative serum B-hCG pregnancy test at screening for women of childbearing potential
  5. Male participants with partners of childbearing potential and female participants of childbearing potential are required to use highly effective contraception methods during the conduct of the study and for 6 months after the last dose of study drug
  6. Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC)
  7. Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2018 as determined by central imaging
  8. Measurable disease as defined by RECIST 1.1 criteria as determined by central imaging
  9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  10. Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN), alkaline phosphatase <2.5 x ULN, and bilirubin ≤1.5 x ULN or in participants with biliary stenting ≤2.0 x ULN
  11. Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin >9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
  12. Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min
  13. Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)

Exclusion Criteria:

  1. Prior chemotherapy or radiation for pancreatic cancer
  2. Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
  3. Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted.
  4. History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
  5. History of allergy or hypersensitivity to any of the chemotherapy agents being prescribed or their excipients
  6. Any medical or surgical condition that may place the participant at increased risk while on study
  7. Any condition potentially decreasing compliance to study procedures
  8. Exposure to another investigational drug within 28 days of first dosing visit, or 5 half-lives of the investigational drug (whichever is longer)
  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infections, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  10. Documented history of drug or alcohol abuse within 6 months of signing informed consent
  11. Any medical condition that, in the opinion of the investigator, may pose a safety risk to a participant in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation
  12. Participants with a history of interstitial pulmonary disease, hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection
  13. Participants who have been administered a live vaccine within 4 weeks prior to the first administration of therapy
  14. Participants who cannot stop chronic medications that inhibit or induce cytochrome P (CYP) 2C8 or CYP3A4
  15. Participants with poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A
Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX
Drug: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX

Drug: Pamrevlumab is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil.

Other Names:
  • Gemzar
  • Abraxane
  • 5-Fluracil
  • Leucovorin
  • Camptosar
  • Efudex
  • Eloxitan
  • FG-3019
Placebo Comparator: Arm B
Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
Drug: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX

Drug: Placebo is administered on Days 1, 8 and 15 of Treatment Cycle 1 and on Day 1 and 15 of each subsequent treatment cycle via IV infusion.

Drug: Gemcitabine is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: Nab-paclitaxel is administered on Days 1, 8 and 15 of each 28 day treatment cycle via IV infusion.

Drug: FOLFIRINOX is a combination of several agents administered on Days 1 and 15 of each 28 day treatment cycle via IV infusion. The specific agents are Oxaliplatin, Folinic Acid, Irinotecan, and Fluorouracil.

Other Names:
  • Gemzar
  • Abraxane
  • 5-Fluracil
  • Leucovorin
  • Camptosar
  • Efudex
  • Eloxitan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: Up to approximately 5 years
Overall survival was defined as the time from date of randomization to date of death due to any cause. Overall survival was calculated using the Kaplan-Meier method.
Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival (EFS)
Time Frame: Up to approximately 5 years
The EFS endpoint was a composite time-to-event endpoint. The event being analyzed ('treatment failure') was defined as the earliest occurrence of: a) failure to achieve disease-free status locally after completion of neoadjuvant treatment and/or after surgery (that is, resection failure or progression that precludes surgery); b) local or distant recurrence, or c) death. The EFS was calculated using the Kaplan-Meier method.
Up to approximately 5 years
Progression-free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: Up to approximately 5 years
The PFS was defined as time from date of randomization until disease progression or death due to any cause, whichever occurred first. PFS was calculated using the Kaplan-Meier method. Progression was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 millimeters (mm). Unequivocal progression of existing non-target lesions and the appearance of one or more new lesions was also considered progression.
Up to approximately 5 years
Number of Participants With Best Overall Objective Response as Assessed Using RECIST v1.1
Time Frame: Up to approximately 5 years
Best overall objective response was defined as a complete response (CR) or partial response (PR). CR was defined as disappearance of all target or non-target lesions and normalization of tumor marker level (for non-target lesions), any pathological lymph nodes (whether target or non-target) must have reduced in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Up to approximately 5 years

Collaborators and Investigators

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

Sponsor

FibroGen

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.

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)

May 10, 2019

Primary Completion (Actual)

June 11, 2024

Study Completion (Actual)

June 11, 2024

Study Registration Dates

First Submitted

May 2, 2019

First Submitted That Met QC Criteria

May 5, 2019

First Posted (Actual)

May 7, 2019

Study Record Updates

Last Update Posted (Actual)

November 5, 2024

Last Update Submitted That Met QC Criteria

October 15, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FGCL-3019-087

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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