Study of Pegilodecakin (LY3500518) With FOLFOX Compared to FOLFOX Alone Second-line Tx in Participants With Metastatic Pancreatic Cancer
- Conditions
- Pancreatic Cancer
- Interventions
- Drug: FOLFOXBiological: Pegilodecakin
- Registration Number
- NCT02923921
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
To compare the efficacy of pegilodecakin in combination with FOLFOX versus FOLFOX alone in participants with metastatic pancreatic cancer as measured by overall survival.
- Detailed Description
This is an open-label, multi-center, randomized, Phase 3 study designed to compare the efficacy and safety of pegilodecakin in combination with FOLFOX versus FOLFOX alone in participants with metastatic adenocarcinoma of the pancreas who have progressed on one prior gemcitabine containing regimen.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 567
- The presence of metastatic pancreatic adenocarcinoma
- Measurable disease per RECIST v.1.1
- Participant must have documented tumor progression during or following a gemcitabine containing regimen to treat metastatic disease as established by CT or MRI scan
- Eastern Cooperative Oncology Group Performance Status of 0 - 1
- Participant must have completed prior chemotherapy at least 2 weeks (washout period) prior to randomization and recovered from toxicity to Grade 1 or baseline
- Participants must not have received previous radiation therapy or investigational therapy for the treatment of advanced metastatic disease.
- Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study
- No peripheral neuropathy
- No known history of dihydropyrimidine dehydrogenase deficiency
- Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non- adenocarcinoma (i.e., lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma
- Participant on Coumadin and not willing to change to LMWH or oral Factor II or Xa inhibitor with half-life of less than 24 hours.
- Participant has received prior treatment with pegilodecakin or fluoropyrimidine/platinum containing regimen
- Participants who were intolerant of a gemcitabine containing regimen.
- History of positivity for human immunodeficiency virus
- Chronic active or active viral hepatitis A, B, or C infection
- Clinically significant bleeding within two weeks prior to randomization (e.g., gastrointestinal (GI) bleeding, intracranial hemorrhage)
- Pregnant or lactating women
- Participants with a history of immune-mediated neurological disorders such as multiple sclerosis, Guillain-Barré or inflammatory CNS/PNS disorders
- Clinically significant ascites defined as requiring ≥ 1 paracentesis every 2- weeks
- Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy),within 28 days prior to randomization or anticipated surgery during the study period
- Prior history of receiving immune modulators including, but not limited to, anti-CTLA4, anti-PD1, anti-PD-L1
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOX FOLFOX FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5-FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. Pegilodecakin + FOLFOX FOLFOX Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing ≤80 kg or 0.8 mg for participants weighing\>80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX \[dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2\] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression \[that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity\], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing\>80 kg. Pegilodecakin + FOLFOX Pegilodecakin Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing ≤80 kg or 0.8 mg for participants weighing\>80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX \[dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2\] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression \[that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity\], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing\>80 kg.
- Primary Outcome Measures
Name Time Method Overall Survival Randomization to date of death from any cause (Up To 30 Months) Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator Randomization to PD (Up To 30 Months) ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response.
Percentage of Participants Alive at 1 Year (12-Month Survival Rate) From randomization to until the date of first documented date of death from any cause within 12 months The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization.
Progression Free Survival Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months) PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant.
Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR) Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up To 30 Months) Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Duration of Response (DOR) Randomization to Progressive Disease (PD) or Date of Death (Up To 30 Months) DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Trial Locations
- Locations (130)
Texas Oncology - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology PLLC
🇺🇸Nashville, Tennessee, United States
University of Utah School of Medicine
🇺🇸Salt Lake City, Utah, United States
St John of God Murdoch Hospital
🇦🇺Murdoch, Western Australia, Australia
Universitätsklinikum Salzburg
🇦🇹Salzburg, Austria
McGill University
🇨🇦Montreal, Quebec, Canada
Arcispedale Santa Maria Nuova Azienda Ospedaliera di Reggio Emilia
🇮🇹Reggio Emilia, Italy
Universitair Ziekenhuis Brussel
🇧🇪Brussel, Belgium
Universitätsklinikum Graz
🇦🇹Graz, Steiermark, Austria
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Korea, Republic of
Szp.Kliniczny Przemienienia Panskiego UM im.K.Marcinkowskieg
🇵🇱Poznan, Poland
Addenbrookes Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Hematology Oncology Clinic
🇺🇸Baton Rouge, Louisiana, United States
CHU la Miletrie
🇫🇷Poitiers, France
Lynn Cancer Institute Ctr for Hem-Onc
🇺🇸Boca Raton, Florida, United States
Universita Campus Biomedico
🇮🇹Roma, Italy
Cabrini Hospital Malvern
🇦🇺Malvern, Victoria, Australia
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Hospital Universitaire Erasme Brussel
🇧🇪Brussel, Belgium
AZ Groeninge
🇧🇪Kortrijk, Belgium
Clinique St Elisabeth Namur
🇧🇪Namur, Belgium
Kliniken Essen-Mitte Ev. Huyssens-Stiftung
🇩🇪Essen, Nordrhein-Westfalen, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Policlinico San Matteo
🇮🇹Pavia, Italy
Hospital Duran I Reynals
🇪🇸Hospitaled DE Llobre, Barcelona, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
University of Massachusetts Medical Center
🇺🇸Worcester, Massachusetts, United States
Warringal Private Hospital
🇦🇺Heidelberg, Victoria, Australia
Asklepios Klinik Altona
🇩🇪Hamburg, Germany
Grand Hopital de Charleroi-Site Notre-Dame
🇧🇪Charleroi, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
CHU de Besancon Hopital Jean Minjoz
🇫🇷Besancon Cedex, France
Hopital de la Pitie Salpetriere
🇫🇷Paris CEDEX 13, France
TRIO - Translational Research in Oncology-US, Inc.
🇺🇸Los Angeles, California, United States
Cancer Treatment Centers of America
🇺🇸Goodyear, Arizona, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Watson Clinic
🇺🇸Lakeland, Florida, United States
Saint Alphonsus Regional Medical Center
🇺🇸Caldwell, Idaho, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
St. Joseph Heritage Healthcare
🇺🇸Fullerton, California, United States
Memorial Regional Hospital/Joe Dimaggio Childrens Hospital
🇺🇸Hollywood, Florida, United States
Northeast Georgia Cancer Care, LLC
🇺🇸Athens, Georgia, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
US Oncology
🇺🇸The Woodlands, Texas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
New England Cancer Specialists - Scarborough
🇺🇸Scarborough, Maine, United States
Summit Medical Group
🇺🇸Summit, New Jersey, United States
Committee on Clinical Investigations (CCI)- Beth Isreal Deaconess Medical Center IRB
🇺🇸Boston, Massachusetts, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
St Louis Cancer Care
🇺🇸Bridgeton, Missouri, United States
Imeldaziekenhuis
🇧🇪Bonheiden, Belgium
Texas Oncology-Austin Midtown
🇺🇸Austin, Texas, United States
North Shore Hematology Oncology Associates
🇺🇸East Setauket, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
St Vincent's Hospital
🇦🇺Sydney, New South Wales, Australia
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Medical Oncology Associates, PS
🇺🇸Spokane, Washington, United States
CHU Dinant Godinne - UCL Namur
🇧🇪Yvoir, Belgium
KH der Barmherzigen Schwestern Linz BetriebsGesmbH
🇦🇹Linz, Oberösterreich, Austria
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro
🇮🇹Candiolo, Torino, Italy
Ospedale le Torrette
🇮🇹Ancona, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
AOU dell'Università degli Studi della Campania Luigi Vanvitelli
🇮🇹Naples, Italy
Städtisches Klinikum München
🇩🇪München, Bayern, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Toronto Sunnybrook Regional Cancer Center
🇨🇦Toronto, Ontario, Canada
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
St Josef-Hospital Bochum
🇩🇪Bochum, Germany
Istituto Scientifico Romagnolo - Studio e la Cura dei Tumori
🇮🇹Meldola, Forli, Italy
Azienda Ospedaliera Universitaria Ospedale San Martino di Genova
🇮🇹Genova, Italy
Ospedale Niguarda Ca Granda
🇮🇹Milano, Italy
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Jeonnam, Korea, Republic of
Centrum Medyczne Medyk
🇵🇱Rzeszow, Poland
Dong-A University Medical Center
🇰🇷Busan, Busan Gwang'yeogsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Korea, Republic of
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, La Coruna, Spain
Wojewodzki Szpital Zespolony
🇵🇱Torun, Poland
C.H. Regional Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Germans Trias i Pujol
🇪🇸Barcelona, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
University College London Hospital Foundation Trust
🇬🇧London, Surrey, United Kingdom
Regional University Hospital in Malaga
🇪🇸Malaga, Spain
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Tri-Service General Hospital
🇨🇳Neihu Taipei, Taiwan
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Guys/St. Thomas Hospital
🇬🇧London, Surrey, United Kingdom
USC Norris Cancer Hospital
🇺🇸Los Angeles, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
St. Elizabeth Medical Center
🇺🇸Edgewood, Kentucky, United States
Eastern Regional Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Hope Cancer Center of East Texas
🇺🇸Tyler, Texas, United States
Texas Oncology-Wichital Falls Texoma Cancer Center
🇺🇸Wichita Falls, Texas, United States
Virginia Cancer Institute
🇺🇸Richmond, Virginia, United States
MultiCare Regional Cancer Center - Auburn
🇺🇸Tacoma, Washington, United States
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario Alicante
🇪🇸Alicante, Spain
Hospital General Yague
🇪🇸Burgos, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Madrid Norte Sanchinarro
🇪🇸Madrid, Spain
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Arizona Cancer Center
🇺🇸Phoenix, Arizona, United States
UF Health Cancer Center- Orlando Health
🇺🇸Orlando, Florida, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Florida Hospital Cancer Institute
🇺🇸Orlando, Florida, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Novant Health, Oncology Research Institute
🇺🇸Winston-Salem, North Carolina, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Fort Wayne Oncology & Hematology
🇺🇸Fort Wayne, Indiana, United States
Hôpital Nord Franche-Comté
🇫🇷Trevenans, France
Velindre Hospital
🇬🇧Cardiff, South Glamorgan, United Kingdom
Hammersmith Hospital
🇬🇧Acton, London, United Kingdom
Aurora West Allis Medical Center
🇺🇸Green Bay, Wisconsin, United States
Cancer Care Associates Medical Group
🇺🇸Redondo Beach, California, United States
Central Coast Medical Oncology Corporation
🇺🇸Santa Maria, California, United States
Texas Oncology-Plano East
🇺🇸Plano, Texas, United States