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

NCT04233866

Description:

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.

Related Conditions:
  • Pancreatic Acinar Cell Carcinoma
  • Pancreatic Adenocarcinoma
  • Pancreatic Adenosquamous Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread
  • Official Title: A Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel Compared With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan in Older Patients With Treatment Naïve Metastatic Pancreatic Cancer (GIANT)

Clinical Trial IDs

  • ORG STUDY ID: EA2186
  • SECONDARY ID: NCI-2019-08286
  • SECONDARY ID: EA2186
  • SECONDARY ID: EA2186
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT04233866

Conditions

  • Metastatic Pancreatic Adenocarcinoma
  • Stage IV Pancreatic Cancer AJCC v8

Interventions

DrugSynonymsArms
Fluorouracil5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757Arm B (fluorouracil, leucovorin, liposomal irinotecan)
GemcitabinedFdC, dFdCyd, DifluorodeoxycytidineArm A (gemcitabine, nab-paclitaxel)
Gemcitabine HydrochloridedFdCyd, Difluorodeoxycytidine Hydrochloride, FF 10832, FF-10832, FF10832, Gemcitabine HCI, Gemzar, LY-188011, LY188011Arm A (gemcitabine, nab-paclitaxel)
LeucovorinFolinic acidArm B (fluorouracil, leucovorin, liposomal irinotecan)
Leucovorin CalciumAdinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, WellcovorinArm B (fluorouracil, leucovorin, liposomal irinotecan)
Liposomal IrinotecanIrinotecan Liposome, MM-398, nal-IRI, Nanoliposomal Irinotecan, Nanoparticle Liposome Formulation of Irinotecan, Onivyde, PEP02Arm B (fluorouracil, leucovorin, liposomal irinotecan)
Nab-paclitaxelABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxelArm A (gemcitabine, nab-paclitaxel)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (gemcitabine, nab-paclitaxel)ExperimentalPatients 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.
  • Gemcitabine
  • Gemcitabine Hydrochloride
  • Nab-paclitaxel
Arm B (fluorouracil, leucovorin, liposomal irinotecan)ExperimentalPatients 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.
  • Fluorouracil
  • Leucovorin
  • Leucovorin Calcium
  • Liposomal Irinotecan

Eligibility Criteria

        Inclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 2 years post treatment
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Instrumental Activities of Daily Living (IADL)
Time Frame:Up to 2 years post treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ECOG-ACRIN Cancer Research Group

Last Updated

June 19, 2020