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 Pancreatic Cancer

Pancreatic Cancer Non-resectable Clinical Trial

— LAPIS  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03941093
• Other study ID #: FGCL-3019-087
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 10, 2019
• Est. completion date: April 30, 2024

Study information

• Verified date: January 2024
• Source: FibroGen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 284
• Est. completion date: April 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer Non-resectable
• Pancreatic Neoplasms

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  China,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		Randomization to death due to any cause or until the last participant to complete treatment reaches 18 months post-treatment
Secondary	Event-free survival (EFS)		Randomization until one of the following events, whichever occurs first: resection failure or progression that precludes surgery, local or distant recurrence, death (assessed up to 6 years)
Secondary	Progression-free survival (PFS)		Randomization until disease progression or death, whichever occurs first (assessed up to 6 years)
Secondary	Best Overall Objective Response Rate (ORR), as Assessed Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Best ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) during treatment period.	Randomization until centrally-assessed progressive disease (PD), death, or first administration of anti-tumor treatment (other than study medication), whichever occurs first (assessed up to 6 years)

External Links

•   Link to sponsor website