FOLFOX-D: Phase II Study of 5-FU, Oxaliplatin Plus Dasatinib in Metastatic Pancreatic Adenocarcinoma

Sponsor
University of Florida (Other)
Overall Status
Completed
CT.gov ID
NCT01652976
Collaborator
Bristol-Myers Squibb (Industry)
44
1
1
96
0.5

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if the study drug, dasatinib, given in combination with 5-Fluorouracil, leucovorin and oxaliplatin (FOLFOX) will work against metastatic pancreatic cancer.

Dasatinib is a Food and Drug Administration (FDA) approved drug for treating chronic myelogenous leukemia and acute lymphoblastic leukemia, however it is not currently approved for use in the treatment of pancreatic cancer.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Systemic control of pancreatic cancer remains a clinical unmet need. The recent superiority of 5-FU based combination therapies over the historical standard gemcitabine represents an opportunity to develop novel combinations of synergistic and effective cytotoxic and biologic targeted therapies. Src excess activity has been demonstrated in pancreatic cancer and is implicated in the invasive and metastatic phenotype clearly represented by this disease. Inhibition of Src activity is associated with numerous biologic modifications capable of positively modifying this phenotype and appears to have synergy with restoring inherent chemosensitivity. The addition of dasatinib to FOLFOX (FOLFOX-D) represents a novel therapeutic regimen in pancreatic cancer with safety and pharmacokinetic data already having been established in colorectal cancer. This protocol will test the safety and activity of this combination in pancreatic cancer where current clinical outcomes remain far from optimal.

Study Design

Study Type:
Interventional
Actual Enrollment :
44 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of 5-Fluorouracil, Oxaliplatin Plus Dasatinib (FOLFOX-D) in First-line Metastatic Pancreatic Adenocarcinoma
Actual Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
Feb 1, 2018
Actual Study Completion Date :
Jul 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Arm

Dasatinib and mFOLFOX6

Drug: Dasatinib
Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle
Other Names:
  • Sprycel
  • Drug: mFOLFOX6
    mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Other Names:
  • Oxaliplatin
  • Leucovorin
  • 5-Fluorouracil
  • Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [3 years]

      Determine activity of 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus dasatinib on progression free survival (PFS) in patients with metastatic pancreatic adenocarcinoma

    Secondary Outcome Measures

    1. Response Rate [3 years]

      To determine the response rate (RR) by RECIST 1.1 criteria. The response rate is the number of subjects who had either a complete or partial response by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). The imaging modality used for all RECIST assessments in this study was CT.

    2. Freedom From Metastasis [3 years]

      To determine the rate of freedom from metastasis (FFM), which is defined as the percentage of subjects with documented progressive disease (by RECIST 1.1 criteria) who had no new lesions. RECIST 1.1 criteria defines progressive disease as the appearance of one or more new lesions and/or the increase of the sum of the largest diameter of the target lesions by at least 20% from the smallest sum collected (the sum must also have increased by at least 5 mm).

    3. Median Time To Progression [3 years]

      To determine the median time to progression (TTP). TTP is defined as the time (in months) from when a subject achieves either a complete or partial response by RECIST 1.1 criteria until progressive disease (by RECIST 1.1 criteria) or death occurs.

    4. Median Overall Survival [4 years]

      To determine median overall survival (OS) in months

    5. Clinical Benefit Rate [3 years]

      To determine the clinical benefit rate (CBR). The CBR is defined as the percentage of subjects who achieved either a complete or partial response or stable disease by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). By RECIST 1.1 criteria, a subject is considered to have stable disease when the sum of the largest diameter of the target lesions has neither decreased enough to qualify as a partial response not increased enough to qualify as progressive disease.

    6. Site of Failure [3 years]

      To determine the site of failure of this regimen in this population. The site of failure is the anatomical site(s) where disease progression by RECIST 1.1 criteria was noted on imaging.

    7. Safety and Tolerability [3 years]

      To determine the safety profile and tolerability of this regimen in this population by evaluating acute treatment related toxicities using CTCAE v4.0 criteria. Using the CTCAE v4.0, the severity of each adverse event reported was graded on a scale of 1 (mild severity) to 5 (fatal). For this outcome measure the percentage of subjects experiencing any adverse event of each CTCAE grade was tabulated.

    8. Drug Compliance [3 years]

      To determine patient compliance with oral therapy. For this outcome measure, compliance with oral therapy is defined as the percentage of subjects that took dasatinib for at least one cycle. Compliance with oral therapy was documented with a medication diary that subjects were asked to complete to document whether each dose of dasatinib was taken.

    9. Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007 [3 years]

      To determine the quality of life (QOL) of patients receiving this therapy using the CTSQ questionnaire. The CTSQ consists of 16 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are used to calculate 3 subscores: Expectations of Therapy (ET), Feelings about Side Effects (FSE), and Satisfaction with Therapy (SWT). Each subscore is calculated by multiplying the mean response value for the questions used to calculate that subscore by 25. The maximum value is 100 and the minimum value is 0 for all 3 subscores. A higher subscore indicates better QOL in that area. The mean difference in each of the 3 subscores from baseline and 95% confidence interval for the entire study population is reported here. A negative mean difference indicates a decrease from baseline in QOL for that area.

    10. Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0) [3 years]

      The FACT-Hep consists of 45 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are summed to calculate 5 subscores: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The mean difference in each of the 5 subscores from baseline, as well as the total score of the 5 subscores (the FACT-Hep Total Score) for the entire study population is reported here. The mean difference in the FACT-G Total Score (calculated by summing the PWB, SWB, EWB, and FWB subscores) is also reported here. A negative mean difference indicates a decrease from baseline in QOL. Score ranges- PWB subscore: 0-28, SWB subscore: 0-28, EWB subscore: 0-24, FWB subscore: 0-28, HCS subscore: 0-72, FACT-G Total Score: 0-108, and FACT-Hep Total Score: 0-180. A higher value for each subscore or total score indicates better QOL.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Pancreatic adenocarcinoma with evidence of metastatic disease on imaging

    • Measurable disease (per RECIST 1.1)

    • ECOG Performance Status 0-2

    • No prior chemotherapy or radiotherapy for metastatic pancreatic cancer. Patients may have received prior treatment for non-metastatic disease; however the diagnosis of metastatic disease must have been made more than 6 months after completion of treatment.

    • Patients may have a history of other malignancies if there is no current evidence of persistent or recurrent disease and they are not undergoing any active therapy (including hormonal)

    • Patent biliary system

    • Patients receiving anti-coagulation treatment with an agent such as Coumadin or heparin may be allowed to participate, provided they are on stable anti-coagulation therapy with no active bleeding and have no condition that carries a high risk of bleeding

    • Adequate organ and marrow function

    • Ability to take oral medication (dasatinib must be swallowed whole)

    • Patient agrees to discontinue prohibited concomitant medications

    • Age > 18 years

    • Women of childbearing potential (WOCBP) must be using an adequate method of contraception throughout the study and for at least 4 weeks after the last dose of study drug.

    • A male subject of fathering potential must use an adequate method of contraception throughout the study and for at least 4 weeks after the last dose of study drug.

    Exclusion Criteria:
    • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug. Women who are pregnant or breastfeeding and sexually active fertile men not using effective birth control if their partners are WOCBP are also excluded.

    • History of known brain metastases or carcinomatous meningitis

    • Recent major surgery (within 4 weeks) or minor surgery (within 2 weeks), excluding placement of a vascular access device or biliary stent

    • Uncontrolled diabetes

    • Any sensory neuropathy > grade 1 at baseline

    • Serious active or uncontrolled infection

    • Concurrent medical condition which may increase the risk of toxicity including clinically significant pleural or pericardial effusion, patients with known DPD deficiency or patients with a history of allergic reactions attributed to oxaliplatin, 5-FU or leucovorin.

    • Cardiac Symptoms including unstable angina or stable angina markedly limiting ordinary physical activity, NYHA class III or IV congestive heart failure, myocardial infarction or stroke within 6 months of study enrollment, diagnosed congenital long QT syndrome, any history of clinically significant ventricular arrhythmias, prolonged QTc interval on pre-entry ECG or clinically significant peripheral vascular disease.

    • Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration

    • History of significant bleeding disorder unrelated to cancer, including diagnosed congenital bleeding disorders, diagnosed acquired bleeding disorder within one year or ongoing or recent (≤ 3 months) significant gastrointestinal bleeding.

    • History of any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of protocol therapy, might affect the interpretation of the results of the study, or that puts the subject at high risk for treatment complications.

    • Use of category I drugs that are generally accepted to have a risk of causing Torsades de Pointes

    • Use of potent CYP3A4 inhibitors that significantly increase dasatinib exposure

    • Prisoners or subjects who are involuntarily incarcerated

    • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

    • Inability to comply with study and/or follow-up procedures

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UF Health Cancer Center Gainesville Florida United States 32610

    Sponsors and Collaborators

    • University of Florida
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Thomas J George, Jr., MD, FACP, University of Florida

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT01652976
    Other Study ID Numbers:
    • IRB201600540
    • CA180-359
    • OCR11303
    First Posted:
    Jul 30, 2012
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Dec 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by University of Florida
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Period Title: Overall Study
    STARTED 44
    COMPLETED 44
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Treatment Arm
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Overall Participants 44
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    65
    Sex: Female, Male (Count of Participants)
    Female
    15
    34.1%
    Male
    29
    65.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    2
    4.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    4
    9.1%
    White
    38
    86.4%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    44
    100%
    ECOG Performance status (Count of Participants)
    Status = 0
    22
    50%
    Status = 1
    19
    43.2%
    Status = 2
    2
    4.5%
    Performance Status Unknown
    1
    2.3%

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS)
    Description Determine activity of 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus dasatinib on progression free survival (PFS) in patients with metastatic pancreatic adenocarcinoma
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Median (95% Confidence Interval) [months]
    4
    2. Secondary Outcome
    Title Response Rate
    Description To determine the response rate (RR) by RECIST 1.1 criteria. The response rate is the number of subjects who had either a complete or partial response by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). The imaging modality used for all RECIST assessments in this study was CT.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Number (95% Confidence Interval) [percentage of subjects]
    25
    3. Secondary Outcome
    Title Freedom From Metastasis
    Description To determine the rate of freedom from metastasis (FFM), which is defined as the percentage of subjects with documented progressive disease (by RECIST 1.1 criteria) who had no new lesions. RECIST 1.1 criteria defines progressive disease as the appearance of one or more new lesions and/or the increase of the sum of the largest diameter of the target lesions by at least 20% from the smallest sum collected (the sum must also have increased by at least 5 mm).
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed for this outcome measure only includes the 29 participants who had documented disease progression (by RECIST 1.1 criteria) during study participation.
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 29
    Number (95% Confidence Interval) [percentage of subjects]
    65.5
    4. Secondary Outcome
    Title Median Time To Progression
    Description To determine the median time to progression (TTP). TTP is defined as the time (in months) from when a subject achieves either a complete or partial response by RECIST 1.1 criteria until progressive disease (by RECIST 1.1 criteria) or death occurs.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed for this outcome measure includes only the 11 participants who achieved either a complete or partial response by RECIST 1.1 criteria during study participation.
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 11
    Median (90% Confidence Interval) [months]
    9.8
    5. Secondary Outcome
    Title Median Overall Survival
    Description To determine median overall survival (OS) in months
    Time Frame 4 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Median (95% Confidence Interval) [months]
    10.6
    6. Secondary Outcome
    Title Clinical Benefit Rate
    Description To determine the clinical benefit rate (CBR). The CBR is defined as the percentage of subjects who achieved either a complete or partial response or stable disease by RECIST 1.1 criteria. RECIST 1.1 criteria defines a partial response as a decrease of the sum of the largest diameter each target lesion by at least 30%. A complete response is defined as the disappearance of all target lesions (except lymph nodes, whose short axis must measure 10 mm or less). By RECIST 1.1 criteria, a subject is considered to have stable disease when the sum of the largest diameter of the target lesions has neither decreased enough to qualify as a partial response not increased enough to qualify as progressive disease.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Number (95% Confidence Interval) [percentage of subjects]
    56.82
    7. Secondary Outcome
    Title Site of Failure
    Description To determine the site of failure of this regimen in this population. The site of failure is the anatomical site(s) where disease progression by RECIST 1.1 criteria was noted on imaging.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Left pleural effusion
    1
    2.3%
    Liver
    12
    27.3%
    Lungs
    3
    6.8%
    Pancreas/liver
    4
    9.1%
    Peritoneal carcinomatosis
    1
    2.3%
    peritoneal carcinomatosis/liver
    1
    2.3%
    Spleen/liver
    1
    2.3%
    8. Secondary Outcome
    Title Safety and Tolerability
    Description To determine the safety profile and tolerability of this regimen in this population by evaluating acute treatment related toxicities using CTCAE v4.0 criteria. Using the CTCAE v4.0, the severity of each adverse event reported was graded on a scale of 1 (mild severity) to 5 (fatal). For this outcome measure the percentage of subjects experiencing any adverse event of each CTCAE grade was tabulated.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Percent of subjects experiencing a Grade 1 event
    88.6
    Percent of subjects experiencing a grade 2 event
    90.9
    Percent of subjects experiencing a Grade 3 event
    86.4
    Percent of subjects experiencing a Grade 4 event
    22.7
    Percent of subjects experiencing a grade 5 event
    9.1
    9. Secondary Outcome
    Title Drug Compliance
    Description To determine patient compliance with oral therapy. For this outcome measure, compliance with oral therapy is defined as the percentage of subjects that took dasatinib for at least one cycle. Compliance with oral therapy was documented with a medication diary that subjects were asked to complete to document whether each dose of dasatinib was taken.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Number (95% Confidence Interval) [percentage of subjects]
    93.2
    10. Secondary Outcome
    Title Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007
    Description To determine the quality of life (QOL) of patients receiving this therapy using the CTSQ questionnaire. The CTSQ consists of 16 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are used to calculate 3 subscores: Expectations of Therapy (ET), Feelings about Side Effects (FSE), and Satisfaction with Therapy (SWT). Each subscore is calculated by multiplying the mean response value for the questions used to calculate that subscore by 25. The maximum value is 100 and the minimum value is 0 for all 3 subscores. A higher subscore indicates better QOL in that area. The mean difference in each of the 3 subscores from baseline and 95% confidence interval for the entire study population is reported here. A negative mean difference indicates a decrease from baseline in QOL for that area.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Subscore difference for ET
    -8.4
    Subscore difference for FSE
    2.1
    Subscore difference for SWT
    -0.5
    11. Secondary Outcome
    Title Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0)
    Description The FACT-Hep consists of 45 questions where subjects respond with a score on a scale of 0 (worst)-4 (best). The responses to the questions are summed to calculate 5 subscores: Physical Well-Being (PWB), Social Well-Being (SWB), Emotional Well-Being (EWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The mean difference in each of the 5 subscores from baseline, as well as the total score of the 5 subscores (the FACT-Hep Total Score) for the entire study population is reported here. The mean difference in the FACT-G Total Score (calculated by summing the PWB, SWB, EWB, and FWB subscores) is also reported here. A negative mean difference indicates a decrease from baseline in QOL. Score ranges- PWB subscore: 0-28, SWB subscore: 0-28, EWB subscore: 0-24, FWB subscore: 0-28, HCS subscore: 0-72, FACT-G Total Score: 0-108, and FACT-Hep Total Score: 0-180. A higher value for each subscore or total score indicates better QOL.
    Time Frame 3 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Dasatinib and mFOLFOX6
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    Measure Participants 44
    Subscore difference for PWB
    -4.4
    Subscore difference for SWB
    -0.9
    Subscore difference for EWB
    0.6
    Subscore difference for FWB
    -2.8
    Subscore difference for HCS
    -6.3
    Difference in FACT-G Total Score
    -7.4
    Difference in FACT-Hep Total Score
    -13.7

    Adverse Events

    Time Frame Adverse event data were collected from the time that informed consent was signed until 30 days after the last dose of study treatment. During this time frame, adverse event data was collected at the time informed consent was signed, on day 1 of each treatment cycle, and 30 days after the last dose of study treatment at a minimum. The time over which adverse event data was collected for the subjects ranged from 8 days to 44 months, an average of 8.5 months.
    Adverse Event Reporting Description Adverse events were assessed by the principal investigator, the treating sub-investigator, and/or the study coordinator at the time informed consent was signed, on day 1 of each treatment cycle, and 30 days after the last dose of study treatment at a minimum. Adverse events were assessed by physical examination, labs, and subject self-reports.
    Arm/Group Title Treatment Arm
    Arm/Group Description Dasatinib and mFOLFOX6 Dasatinib: Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle mFOLFOX6: mFOLFOX6 (oxaliplatin 85mg/m2 IV, leucovorin 400mg/m2 IV, 5-Fluorouracil bolus 400mg/m2 IV, and 5-Fluorouracil 2400mg/m2 IV) on day 1 of each 14 day cycle
    All Cause Mortality
    Treatment Arm
    Affected / at Risk (%) # Events
    Total 42/44 (95.5%)
    Serious Adverse Events
    Treatment Arm
    Affected / at Risk (%) # Events
    Total 24/44 (54.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 2/44 (4.5%)
    Cardiac disorders
    Atrial fibrillation 1/44 (2.3%)
    Gastrointestinal disorders
    Gastritis 1/44 (2.3%)
    Abdominal pain 2/44 (4.5%)
    Gastrointestinal disorders, other (gastrointestinal hemorrhage-unknown site) 1/44 (2.3%)
    Abdominal infection 1/44 (2.3%)
    Diarrhea 1/44 (2.3%)
    Nausea 3/44 (6.8%)
    Vomiting 3/44 (6.8%)
    Small intestinal obstruction 1/44 (2.3%)
    Ascites 1/44 (2.3%)
    Lower gastrointestinal hemorrhage 1/44 (2.3%)
    Cholangitis 1/44 (2.3%)
    Colitis 1/44 (2.3%)
    Esophageal infection 1/44 (2.3%)
    Oral Mucositis 1/44 (2.3%)
    General disorders
    Non-cardiac chest pain 1/44 (2.3%)
    Fever 1/44 (2.3%)
    Flu-like symptoms 1/44 (2.3%)
    Edema trunk 1/44 (2.3%)
    Infections and infestations
    Sepsis 1/44 (2.3%)
    Injury, poisoning and procedural complications
    Wound dehiscense 1/44 (2.3%)
    Investigations
    Blood bilirubin increased 1/44 (2.3%)
    Metabolism and nutrition disorders
    Hypercalcemia 1/44 (2.3%)
    Dehydration 1/44 (2.3%)
    Nervous system disorders
    Nervous system disorders, other (Stroke-like symptoms) 1/44 (2.3%)
    Subdural hematoma 1/44 (2.3%)
    Renal and urinary disorders
    Renal and urinary disorders, other (kidney stone) 1/44 (2.3%)
    Acute renal injury 1/44 (2.3%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 4/44 (9.1%)
    Upper respiratory infection 1/44 (2.3%)
    Respiratory failure 1/44 (2.3%)
    Respiratory, thoracic, and mediastinal disorders, other (pneumonia) 1/44 (2.3%)
    Other (Not Including Serious) Adverse Events
    Treatment Arm
    Affected / at Risk (%) # Events
    Total 44/44 (100%)
    Blood and lymphatic system disorders
    Anemia 9/44 (20.5%)
    Gastrointestinal disorders
    Vomiting 26/44 (59.1%)
    Oral Pain 5/44 (11.4%)
    Nausea 31/44 (70.5%)
    Mucositis oral 17/44 (38.6%)
    Hemorrhoids 3/44 (6.8%)
    Gastroesophageal reflux disease 3/44 (6.8%)
    Diarrhea 24/44 (54.5%)
    Constipation 19/44 (43.2%)
    Bloating 4/44 (9.1%)
    Ascites 5/44 (11.4%)
    Abdominal distension 4/44 (9.1%)
    Abdominal pain 18/44 (40.9%)
    General disorders
    Pain 3/44 (6.8%)
    Localized edema 3/44 (6.8%)
    General disorders and administrative site conditions - other 3/44 (6.8%)
    Flu-like symtoms 4/44 (9.1%)
    Fever 11/44 (25%)
    Fatigue 32/44 (72.7%)
    Edema limbs 7/44 (15.9%)
    Chills 5/44 (11.4%)
    Infections and infestations
    Upper respiratory tract infection 7/44 (15.9%)
    Injury, poisoning and procedural complications
    Fall 3/44 (6.8%)
    Investigations
    Weight Loss 11/44 (25%)
    Platelet count decreased 8/44 (18.2%)
    Neutrophil count decreased 15/44 (34.1%)
    Metabolism and nutrition disorders
    Hyponatremia 4/44 (9.1%)
    Hypokalemia 4/44 (9.1%)
    Dehydration 4/44 (9.1%)
    Anorexia 21/44 (47.7%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 3/44 (6.8%)
    Back Pain 5/44 (11.4%)
    Nervous system disorders
    Peripheral sensory Neuropathy 30/44 (68.2%)
    Parasthesia 3/44 (6.8%)
    Headache 6/44 (13.6%)
    Dysgeusia 12/44 (27.3%)
    Dysethesia 3/44 (6.8%)
    Dizziness 7/44 (15.9%)
    Psychiatric disorders
    Insomnia 8/44 (18.2%)
    Depression 4/44 (9.1%)
    Anxiety 9/44 (20.5%)
    Renal and urinary disorders
    Urinary frequency 4/44 (9.1%)
    Respiratory, thoracic and mediastinal disorders
    Sore throat 3/44 (6.8%)
    Pleural effusion 9/44 (20.5%)
    Hiccups 4/44 (9.1%)
    Epistaxis 4/44 (9.1%)
    Dyspnea 9/44 (20.5%)
    Cough 3/44 (6.8%)
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous disorders, other 5/44 (11.4%)
    Rash maculo-papular 7/44 (15.9%)
    Periorbital edema 6/44 (13.6%)
    Palmar-plantar erythrodysesthesia syndrome 3/44 (6.8%)
    Vascular disorders
    Hypertension 4/44 (9.1%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Allison Allegra
    Organization University of Florida
    Phone 352-294-5691
    Email allisonallegra3@ufl.edu
    Responsible Party:
    University of Florida
    ClinicalTrials.gov Identifier:
    NCT01652976
    Other Study ID Numbers:
    • IRB201600540
    • CA180-359
    • OCR11303
    First Posted:
    Jul 30, 2012
    Last Update Posted:
    Jan 5, 2021
    Last Verified:
    Dec 1, 2020