A Phase 2 interventional study of Dasatinib and mFOLFOX6 in Pancreatic Cancer Metastatic, sponsored by University of Florida. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-01-05.
Sponsored by University of Florida · Phase 2, Interventional, and Treatment
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.
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.
2,004 studies on the registry are indexed under Adenocarcinoma; 374 are open to participants now.
This study's enrollment of 44 is close to the median of 45 across 1,553 interventional studies indexed under Adenocarcinoma.
Browse Adenocarcinoma studies →University of Florida is the lead sponsor of 1,254 studies on the registry; 201 are open to participants now.
Of its 170 completed or terminated interventional studies of FDA-regulated products, 136 (80%) have results posted.
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Exclusion Criteria:
Dasatinib and mFOLFOX6
Drug: Dasatinib · Drug: mFOLFOX6
Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle
Also known as: Sprycel
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
Also known as: Oxaliplatin, Leucovorin, 5-Fluorouracil
Progression Free Survival (PFS)
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
Response Rate
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
Freedom From Metastasis
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
Median Time To Progression
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
Median Overall Survival
To determine median overall survival (OS) in months
Time frame: 4 years
Clinical Benefit Rate
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
Site of Failure
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
Safety and Tolerability
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
Drug Compliance
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
Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007
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
Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0)
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
| Milestone | Dasatinib and mFOLFOX6 |
|---|---|
| Started | 44 |
| Completed | 44 |
| Not completed | 0 |
Determine activity of 5-Fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus dasatinib on progression free survival (PFS) in patients with metastatic pancreatic adenocarcinoma
| months | Dasatinib and mFOLFOX6 |
|---|---|
| Progression Free Survival (PFS) | 4 (2.3 to 8.5) |
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.
| percentage of subjects | Dasatinib and mFOLFOX6 |
|---|---|
| Response Rate | 25 (13.19 to 40.34) |
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).
| percentage of subjects | Dasatinib and mFOLFOX6 |
|---|---|
| Freedom From Metastasis | 65.5 (45.7 to 82.1) |
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.
| months | Dasatinib and mFOLFOX6 |
|---|---|
| Median Time To Progression | 9.8 (8.6 to 19.5) |
To determine median overall survival (OS) in months
| months | Dasatinib and mFOLFOX6 |
|---|---|
| Median Overall Survival | 10.6 (6.9 to 12.7) |
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.
| percentage of subjects | Dasatinib and mFOLFOX6 |
|---|---|
| Clinical Benefit Rate | 56.82 (41.03 to 71.65) |
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.
| Participants | Dasatinib and mFOLFOX6 |
|---|---|
| Left pleural effusion | 1 |
| Liver | 12 |
| Lungs | 3 |
| Pancreas/liver | 4 |
| Peritoneal carcinomatosis | 1 |
| peritoneal carcinomatosis/liver | 1 |
| Spleen/liver | 1 |
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.
| percentage of subjects | Dasatinib and mFOLFOX6 |
|---|---|
| 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 |
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.
| percentage of subjects | Dasatinib and mFOLFOX6 |
|---|---|
| Drug Compliance | 93.2 (81.3 to 98.6) |
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.
| score on a scale | Dasatinib and mFOLFOX6 |
|---|---|
| Subscore difference for ET | -8.4 (-16.5 to -0.4) |
| Subscore difference for FSE | 2.1 (-8.1 to 12.3) |
| Subscore difference for SWT | -0.5 (-8.8 to 7.8) |
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.
| score on a scale | Dasatinib and mFOLFOX6 |
|---|---|
| Subscore difference for PWB | -4.4 (-6.7 to -2.1) |
| Subscore difference for SWB | -0.9 (-2.5 to 0.8) |
| Subscore difference for EWB | 0.6 (-1.1 to 2.3) |
| Subscore difference for FWB | -2.8 (-4.6 to -1.0) |
| Subscore difference for HCS | -6.3 (-9.3 to -3.4) |
| Difference in FACT-G Total Score | -7.4 (-11.9 to -2.9) |
| Difference in FACT-Hep Total Score | -13.7 (-20.0 to -7.4) |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Arm | 42/44 (95.5%) | 24/44 (54.5%) | 44/44 (100%) |
| Event | Treatment Arm |
|---|---|
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 4/44 |
| NauseaGastrointestinal disorders | 3/44 |
| VomitingGastrointestinal disorders | 3/44 |
| Abdominal painGastrointestinal disorders | 2/44 |
| Febrile neutropeniaBlood and lymphatic system disorders | 2/44 |
| Nervous system disorders, other (Stroke-like symptoms)Nervous system disorders | 1/44 |
| GastritisGastrointestinal disorders | 1/44 |
| Upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 1/44 |
| Blood bilirubin increasedInvestigations | 1/44 |
| Gastrointestinal disorders, other (gastrointestinal hemorrhage-unknown site)Gastrointestinal disorders | 1/44 |
| Event | Treatment Arm |
|---|---|
| FatigueGeneral disorders | 32/44 |
| NauseaGastrointestinal disorders | 31/44 |
| Peripheral sensory NeuropathyNervous system disorders | 30/44 |
| VomitingGastrointestinal disorders | 26/44 |
| DiarrheaGastrointestinal disorders | 24/44 |
| AnorexiaMetabolism and nutrition disorders | 21/44 |
| ConstipationGastrointestinal disorders | 19/44 |
| Abdominal painGastrointestinal disorders | 18/44 |
| Mucositis oralGastrointestinal disorders | 17/44 |
| Neutrophil count decreasedInvestigations | 15/44 |
| Age, Continuous(years) | Treatment Arm |
|---|---|
| Median | 65 (29 to 81) |
| Sex: Female, Male(Participants) | Treatment Arm |
|---|---|
| Female | 15 |
| Male | 29 |
| Race (NIH/OMB)(Participants) | Treatment Arm |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 38 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Treatment Arm |
|---|---|
| United States | 44 |
| ECOG Performance status(Participants) | Treatment Arm |
|---|---|
| Status = 0 | 22 |
| Status = 1 | 19 |
| Status = 2 | 2 |
| Performance Status Unknown | 1 |
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