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)
• Enrollment: 44
• Location: 1
• Arm: 1
• Actual Duration (Months): 96
• Patients Per Site Per Month: 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
Pancreatic Cancer Metastatic	Drug: Dasatinib; Drug: mFOLFOX6	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)

• Study Protocol and Statistical Analysis Plan - Jul 26, 2018

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: Metastatic; Pancreatic Cancer; Adenocarcinoma
• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Leucovorin; Fluorouracil; Oxaliplatin; Dasatinib

Study Results

Participant Flow

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.