Clinical trial NCT03941093: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer Non-resectable
Keywords: locally advanced pancreatic cancer
unresectable pancreatic cancer
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2019-05-07
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with G/NP or FOLFIRINOX or placebo with G/NP or FOLFIRINOX.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Survival
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: Event-free Survival (EFS)
timeFrame: Up to approximately 5 years
measure: Progression-free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Up to approximately 5 years
measure: Number of Participants With Best Overall Objective Response as Assessed Using RECIST v1.1
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Elmhurst
country: United States
facility: Elmhurst Memorial Hospital - Nancy W. Knowles Cancer Center
state: Illinois
city: Naperville
country: United States
facility: Edward Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Comprehensive Cancer Center
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute, Audubon Hospital Campus
state: Kentucky
city: South Portland
country: United States
facility: Maine Health Cancer Care
state: Maine
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: West Reading
country: United States
facility: Reading Hospital McGlinn Cancer Institute
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Temple
country: United States
facility: Baylor Scott & White Medical Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinic
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Brussels
country: Belgium
facility: CUB Hôpital Erasme
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre/University Health Network
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Dongcheng
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Xi'an
country: China
facility: The First Affiliated Hospital Of Xi'an Jiaotong University
state: Shaanxi
city: Jing'an
country: China
facility: Huashan Hospital affiliated with Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School Of Medicine
city: Besançon Cedex
country: France
facility: CHRU Jean Minjoz
city: Clermont Ferrand
country: France
facility: CHU Estaing
city: Clichy
country: France
facility: Hopital BEAUJON
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: La Tronche
country: France
facility: CHU Grenoble Alpes
city: Lyon
country: France
facility: Centre Léon Bérard
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpêtrière
city: Pessac
country: France
facility: Haut-Lévêque
city: Saint Herblain Cedex
country: France
facility: Institut de Cancérologie de l'Ouest Pays de Loire
city: Berlin
country: Germany
facility: Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie
city: Dresden
country: Germany
facility: Technische Universität Dresden, Medizinische Klinik und Poliklinik I
city: München
country: Germany
facility: Klinikum der Universität München, Medizinische Klinik und Poliklinik III
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical center Asaf Harofeh
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Kfar Saba
country: Israel
facility: Meir Medical center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Meldola
country: Italy
facility: Instituto Scientifico Romagnolog per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Grande Ospedale Metropolitano Niguarda, Oncologia Medica Falck
city: Napoli
country: Italy
facility: AOU Federico II
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Verona
country: Italy
facility: CRC di Verona
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Budang Hospital
state: Geyonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Vigo
country: Spain
facility: Alvaro Cunqueiro Hospital
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitaro Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Girona
country: Spain
facility: Institut Catalá d'Oncologia (ICO Girona). Hospital Dr. Josep Trueta
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
References: