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A Study of Cabiralizumab Given With Nivolumab With and Without Chemotherapy in Patients With Advanced Pancreatic Cancer

Phase 2
Completed
Conditions
Advanced Pancreatic Cancer
Interventions
Registration Number
NCT03336216
Lead Sponsor
Bristol-Myers Squibb
Brief Summary

The purpose of this study is to determine whether an investigational immuno-therapy, cabiralizumab in combination with nivolumab, with or without chemotherapy, is effective for the treatment of advanced pancreatic cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
205
Inclusion Criteria
  • Must have histological or cytological confirmed diagnosis of locally advanced or metastatic adenocarcinoma of the pancreas, which has progressed on or after one line of chemotherapy
  • ECOG Performance status 0-1
  • Adequate organ functions
  • Measurable disease
Exclusion Criteria
  • Suspected or known CNS metastasis
  • Participants with active, known, or suspected autoimmune disease
  • Uncontrolled or significant cardiovascular disease
  • Prior exposure to selected immune cell-modulating antibody regimens

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm DNivolumabCabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W
Arm CNivolumabCabiralizumab Q2W + Nivolumab Q4W and Gemcitabine + Nab-Paclitaxel (Abraxane®) D1, 8 and 15 Q4W
Arm ANab-paclitaxelInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm DCabiralizumabCabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W
Arm BCabiralizumabCabiralizumab Q2W + Nivolumab Q4W
Arm BNivolumabCabiralizumab Q2W + Nivolumab Q4W
Arm CCabiralizumabCabiralizumab Q2W + Nivolumab Q4W and Gemcitabine + Nab-Paclitaxel (Abraxane®) D1, 8 and 15 Q4W
Arm CNab-paclitaxelCabiralizumab Q2W + Nivolumab Q4W and Gemcitabine + Nab-Paclitaxel (Abraxane®) D1, 8 and 15 Q4W
Arm AOnivydeInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm DOxaliplatinCabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W
Arm AFluorouracilInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm AGemcitabineInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm ALeucovorinInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm AIrinotecan HydrochlorideInvestigator choice of chemotherapy: Gemcitabine/Nab-Paclitaxel (Abraxane®) or 5-Fluorouracil/Leucovorin/Irinotecan Liposome (ONIVYDE)
Arm CGemcitabineCabiralizumab Q2W + Nivolumab Q4W and Gemcitabine + Nab-Paclitaxel (Abraxane®) D1, 8 and 15 Q4W
Arm DFluorouracilCabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W
Arm DLeucovorinCabiralizumab Q2W + Nivolumab Q4W and Oxaliplatin/5-Flurouracil/Leucovorin (FOLFOX) Q2W
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) by BICRFrom randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)

PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) by InvestigatorFrom randomization date to the date of first objectively documented disease progression or death (up to approximately 65 months)

PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Overall Survival (OS)From randomization to the date of death to any cause (up to approximately 65 months)

OS is defined as the time from randomization to the date of death due to any cause. Based on Kaplan-Meier Estimates.

Progression Free Survival Rate (PFSR) by BICRAt 6, 9, and 12 months

Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Progression Free Survival Rate (PFSR) by InvestigatorAt 6, 9, and 12 months

Progression Free Survival Rates at 6, 9, and 12 months is defined as the percentage of participants who achieve PFS at 6, 9, and 12 months. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The Number of Participants With Adverse Events (AEs) Leading to DiscontinuationFrom first dose to 100 days after last dose of study therapy (up to approximately 51 months)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

The Number of Participants Who Experienced Abnormal Hepatic TestsFrom first dose and 100 days after last dose of study therapy (up to approximately 51 months)

The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study.

Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)

The Number of Participants With On-Treatment Laboratory Abnormalities in Specific Thyroid TestsFrom first dose and 100 days after last dose of study therapy (up to approximately 51 months)

The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study.

Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN) Upper Limit of Normal (ULN)

Objective Response Rate (ORR) by BICRFrom randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Objective Response Rate (ORR) by InvestigatorFrom randomization to the date of objectively documented progression per RECIST v1.1 or the date of subsequent anti-cancer therapy, whichever occurs first (up to approximately 65 months)

ORR is defined as the percentage of participants whose best overall response (BOR) is either CR or PR per response evaluation criteria in solid tumors (RECIST) v1.1 based on Clopper-Pearson method.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Duration of Response (DOR) by BICRFrom randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)

DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by blinded independent central review (BICR) per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

The Number of Participants With Serious Adverse Events (SAEs)From first dose to 100 days after last dose of study therapy (up to approximately 51 months)

A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Duration of Response (DOR) by InvestigatorFrom randomization the date of the first objectively documented tumor progression or death, whichever occurs first (up to approximately 65 months)

DOR for a participant with a best overall response (BOR) of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death, whichever occurs first. Median computed using Kaplan-Meier method.

Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Overall Survival Rates (OSR)At 6 months, 1 year, and 2 years

Overall survival at 6 months, 1 year, and 2 years is defined as the percentage of participants who are alive at 6 months, 1 year, and 2 years. Based on Kaplan-Meier Estimates.

The Number of Participants With Adverse Events (AEs)From first dose to 100 days after last dose of study therapy (up to approximately 51 months)

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.

The Number of Participants Who DiedFrom first dose to 150 days after last dose of study therapy (up to approximately 53 months)

The number of participants that died during the study.

Trial Locations

Locations (41)

Local Institution - 0006

🇺🇸

Philadelphia, Pennsylvania, United States

Local Institution - 0007

🇺🇸

Los Angeles, California, United States

Dana Farber Cancer Institute.

🇺🇸

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Local Institution - 0011

🇺🇸

Houston, Texas, United States

University Of Washington

🇺🇸

Seattle, Washington, United States

Local Institution - 0022

🇯🇵

Chuo-ku, Tokyo, Japan

Local Institution - 0009

🇺🇸

Pittsburgh, Pennsylvania, United States

University Of Colorado

🇺🇸

Aurora, Colorado, United States

Local Institution - 0010

🇺🇸

Boston, Massachusetts, United States

Local Institution - 0001

🇺🇸

Baltimore, Maryland, United States

Local Institution - 0012

🇺🇸

New York, New York, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Local Institution - 0005

🇺🇸

New York, New York, United States

Tennessee Oncology Chattanooga

🇺🇸

Nashville, Tennessee, United States

Local Institution - 0013

🇺🇸

Dallas, Texas, United States

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Local Institution - 0041

🇩🇰

Herlev, Denmark

Local Institution - 0037

🇨🇦

Kingston, Ontario, Canada

Local Institution - 0035

🇨🇦

Toronto, Ontario, Canada

Local Institution - 0032

🇩🇪

Heidelberg, Germany

Universitaetsklinikum Ulm

🇩🇪

Ulm, Germany

Local Institution - 0029

🇩🇪

Mannheim, Germany

Local Institution - 0030

🇩🇪

Wuerzburg, Germany

Local Institution - 0025

🇮🇹

Padova, Italy

Local Institution - 0026

🇮🇹

Roma, Italy

Local Institution - 0021

🇪🇸

Barcelona, Spain

Local Institution - 0017

🇰🇷

Seoul, Korea, Republic of

Local Institution - 0020

🇪🇸

Madrid, Spain

Local Institution - 0034

🇨🇭

Lausanne, Switzerland

Local Institution - 0033

🇨🇭

Chur, Switzerland

Local Institution - 0016

🇬🇧

Glasgow, Lanarkshire, United Kingdom

Local Institution - 0024

🇨🇳

Taipei City, Taiwan

Local Institution - 0031

🇨🇳

Taipei, Taiwan

Local Institution - 0018

🇰🇷

Seoul, Korea, Republic of

Local Institution - 0019

🇪🇸

Madrid, Spain

Florida Cancer Specialists - North

🇺🇸

Saint Petersburg, Florida, United States

Local Institution - 0023

🇯🇵

Kashiwa-shi, Chiba, Japan

Florida Cancer Specialists - South

🇺🇸

Fort Myers, Florida, United States

Mayo Clinic in Rochester, Minnesota

🇺🇸

Phoenix, Arizona, United States

HonorHealth Research Institute

🇺🇸

Scottsdale, Arizona, United States

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