Comparing Two Treatment Combinations, Gemcitabine And Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, And Liposomal Irinotecan For Older Patients With Pancreatic Cancer That Has Spread

Study Overview

Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread

This phase II trial compares two treatment combinations: gemcitabine hydrochloride and nab-paclitaxel, or fluorouracil, leucovorin calcium, and liposomal irinotecan in older patients with pancreatic cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as gemcitabine hydrochloride, nab-paclitaxel, fluorouracil, leucovorin calcium, and liposomal irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study may help doctors find out which treatment combination is better at prolonging life in older patients with metastatic pancreatic cancer.

PRIMARY OBJECTIVE: I. Overall survival. SECONDARY OBJECTIVES: I. Progression-free survival. II. Objective tumor response. III. Comprehensive Geriatric Assessment (CGA)/quality of life (QOL) related objectives: IIIa. Hypothesize that lower scores in functional status assessment tool - instrumental activities of daily living (IADL) will correlate with higher rates of grade 3 or higher chemotherapy toxicity. IV. CGA/QOL related exploratory objectives: IVa. Evaluation of other pre-treatment CGA domains including co-morbidities, depression, nutrition and cognition as predictors of chemotherapy tolerance. IVb. Evaluation of the association between change in functional status during treatment course (comparison between activities of daily living [ADL] and IADL score pre-treatment and at time of disease evaluation) as predictors of chemotherapy tolerance. IVc. Evaluation of the correlation between CGA domains and overall survival by treatment arm. IVd. Evaluation of the difference in QOL scores (Functional Assessment of Cancer Therapy - Hepatitis [FACT-Hep] version 4) between baseline measures and assessment during treatment course between by treatment arms. V. Focused evaluation of toxicities that are of interest for older patients including: peripheral neuropathy, fatigue, falls, emergency room visits, hospitalization, treatment modification and discontinuation. VI. Imaging correlative study objectives: VIa. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and rates of grade 3 or higher chemotherapy toxicity experienced on treatment. VIb. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and overall survival among older patients with metastatic pancreatic cancer. VIc. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and geriatric assessment scores evaluating functional status. VII. Laboratory correlative study objectives: VIIa. Evaluation of the correlation between base line levels of biomarkers of aging (CRP and IL-6) and rates of grade 3 or higher chemotherapy toxicity during therapy. VIIb. Evaluation of the correlation between changes in levels of CRP and IL-6 during therapy and rates of grade 3 chemotherapy toxicity. VIIc. Evaluation of the correlation between baseline levels of biomarkers of aging (CRP and IL-6) and overall survival among older patients with metastatic pancreatic cancer. VIId. Evaluation of the correlation between levels of baseline biomarkers of aging (CRP and IL-6) and geriatric assessments scores evaluation functional status. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive gemcitabine intravenously (IV) over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years.

Metastatic Pancreatic Adenocarcinoma
Stage IV Pancreatic Cancer AJCC v8

DRUG: Fluorouracil
DRUG: Gemcitabine
DRUG: Gemcitabine Hydrochloride
DRUG: Leucovorin
DRUG: Leucovorin Calcium
DRUG: Liposomal Irinotecan
DRUG: Nab-paclitaxel
OTHER: Quality-of-Life Assessment
OTHER: Questionnaire Administration

EA2186
NCI-2019-08286 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
EA2186 (OTHER Identifier) (OTHER: ECOG-ACRIN Cancer Research Group)
EA2186 (OTHER Identifier) (OTHER: CTEP)
U10CA180820 (U.S. NIH Grant/Contract)

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-01-16	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-12-26
First Submitted that Met QC Criteria 2020-01-16	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-12-30
First Posted (ACTUAL) 2020-01-18	Results First Posted N/A	Last Verified 2024-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A (gemcitabine, nab-paclitaxel) Patients receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.	DRUG: Gemcitabine Given IV DRUG: Gemcitabine Hydrochloride Given IV DRUG: Nab-paclitaxel Given IV OTHER: Quality-of-Life Assessment Ancillary studies OTHER: Questionnaire Administration Ancillary studies
EXPERIMENTAL: Arm B (fluorouracil, leucovorin, liposomal irinotecan) Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptab	DRUG: Fluorouracil Given IV DRUG: Leucovorin Given IV DRUG: Leucovorin Calcium Given IV DRUG: Liposomal Irinotecan Given IV OTHER: Quality-of-Life Assessment Ancillary studies OTHER: Questionnaire Administration Ancillary studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm A (gemcitabine, nab-paclitaxel)

Patients receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

DRUG: Gemcitabine

Given IV

DRUG: Gemcitabine Hydrochloride

Given IV

DRUG: Nab-paclitaxel

Given IV

OTHER: Quality-of-Life Assessment

Ancillary studies

OTHER: Questionnaire Administration

Ancillary studies

EXPERIMENTAL: Arm B (fluorouracil, leucovorin, liposomal irinotecan)

Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptab

DRUG: Fluorouracil

Given IV

DRUG: Leucovorin

Given IV

DRUG: Leucovorin Calcium

Given IV

DRUG: Liposomal Irinotecan

Given IV

OTHER: Quality-of-Life Assessment

Ancillary studies

OTHER: Questionnaire Administration

Ancillary studies

Primary Outcome Measures	Measure Description	Time Frame
Overall survival (OS)	Will use a stratified log rank test with one-sided alpha of 0.05 and 90% power. A truncated O'Brien-Fleming boundary will be used to control type I error for efficacy testing and repeated confidence interval methodology on the OS hazard ratio will be used for futility analyses	Up to 2 years post treatment

Secondary Outcome Measures	Measure Description	Time Frame
Instrumental Activities of Daily Living (IADL)	Will evaluate the association between functional status as recorded by the IADL assessment tool and rates of grade 3 or higher chemotherapy toxicity within treatment arm. Will use logistic regression and a 0.025 level one-sided test for the odds ratio.	Up to 2 years post treatment

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
70 Years

Accepts Healthy Volunteers:

Newly diagnosed untreated metastatic adenocarcinoma of the pancreas. However, previous surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided radiation therapy is completed at least 2 weeks prior to registration and adjuvant therapy was administered more than 6 months prior to registration. Patients with the following histology are excluded: acinar cell; adenosquamous carcinoma
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patient is an English speaker with the ability to understand and complete the informed consent and questionnaires
Leukocytes >= 3,000/mcL (obtained within 4 weeks of registration)
Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks of registration)
Platelets >= 100,000/mcL (obtained within 4 weeks of registration)
Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks of registration)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks of registration)
Creatinine =< institutional ULN unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of registration)
Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of registration)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this protocol. HIV positive (+) patients who are on ritonavir or/and cobicistat-based regimen must be switched to alternative anti-retroviral therapy (ART)
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Male patients must agree not to father children while on study
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this protocol, patients should be class 2B or better
Patients must have measurable disease and scans must be done within 4 weeks of registration
Patients classified to have mild-moderate abnormalities in any of the domains evaluated in the screening geriatric assessment and are classified as "vulnerable" are eligible. Patients classified without any abnormalities ("fit") or with severe cognitive/functional impairment or high co-morbidity score ("frail") on the screening geriatric assessment are ineligible
Patients must agree not to take any medications or substances that are strong inhibitors or inducers of CYP3A4. Those who are randomized to liposomal irinotecan treatment arm should avoid drugs that are UGT1A1 inhibitors

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Efrat Dotan, ECOG-ACRIN Cancer Research Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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