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

Brief summary public domain (ClinicalTrials.gov)

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.

Detailed description public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS) [3 years]. Median, months (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=44): 4 (2.3 to 8.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Response Rate [3 years]. Number, percentage of subjects (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=44): 25 (13.19 to 40.34).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Freedom From Metastasis [3 years]. Number, percentage of subjects (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=29): 65.5 (45.7 to 82.1).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Time To Progression [3 years]. Median, months (90% Confidence Interval). Dasatinib and mFOLFOX6 (n=11): 9.8 (8.6 to 19.5).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Median Overall Survival [4 years]. Median, months (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=44): 10.6 (6.9 to 12.7).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Clinical Benefit Rate [3 years]. Number, percentage of subjects (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=44): 56.82 (41.03 to 71.65).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Site of Failure [3 years]. Count Of Participants, Participants. Left pleural effusion: Dasatinib and mFOLFOX6 (n=44): 1. Liver: Dasatinib and mFOLFOX6 (n=44): 12. Lungs: Dasatinib and mFOLFOX6 (n=44): 3. Pancreas/liver: Dasatinib and mFOLFOX6 (n=44): 4. Peritoneal carcinomatosis: Dasatinib and mFOLFOX6 (n=44): 1. peritoneal carcinomatosis/liver: Dasatinib and mFOLFOX6 (n=44): 1. Spleen/liver: Dasatinib and mFOLFOX6 (n=44): 1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Safety and Tolerability [3 years]. Number, percentage of subjects. Percent of subjects experiencing a Grade 1 event: Dasatinib and mFOLFOX6 (n=44): 88.6. Percent of subjects experiencing a grade 2 event: Dasatinib and mFOLFOX6 (n=44): 90.9. Percent of subjects experiencing a Grade 3 event: Dasatinib and mFOLFOX6 (n=44): 86.4. Percent of subjects experiencing a Grade 4 event: Dasatinib and mFOLFOX6 (n=44): 22.7. Percent of subjects experiencing a grade 5 event: Dasatinib and mFOLFOX6 (n=44): 9.1.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Drug Compliance [3 years]. Number, percentage of subjects (95% Confidence Interval). Dasatinib and mFOLFOX6 (n=44): 93.2 (81.3 to 98.6).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quality of Life, as Measured by the Cancer Therapy Satisfaction Questionnaire (CTSQ), 2007 [3 years]. Mean, score on a scale (95% Confidence Interval). Subscore difference for ET: Dasatinib and mFOLFOX6 (n=44): -8.4 (-16.5 to -0.4). Subscore difference for FSE: Dasatinib and mFOLFOX6 (n=44): 2.1 (-8.1 to 12.3). Subscore difference for SWT: Dasatinib and mFOLFOX6 (n=44): -0.5 (-8.8 to 7.8).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Quality of Life, as Measured by the Functional Assessment of Chronic Illness Therapy; Hepatobiliary Cancer (FACT-Hep) Questionnaire (Version 4.0) [3 years]. Mean, score on a scale (95% Confidence Interval). Subscore difference for PWB: Dasatinib and mFOLFOX6 (n=44): -4.4 (-6.7 to -2.1). Subscore difference for SWB: Dasatinib and mFOLFOX6 (n=44): -0.9 (-2.5 to 0.8). Subscore difference for EWB: Dasatinib and mFOLFOX6 (n=44): 0.6 (-1.1 to 2.3). Subscore difference for FWB: Dasatinib and mFOLFOX6 (n=44): -2.8 (-4.6 to -1.0). Subscore difference for HCS: Dasatinib and mFOLFOX6 (n=44): -6.3 (-9.3 to -3.4). Difference in FACT-G Total Score: Dasatinib and mFOLFOX6 (n=44): -7.4 (-11.9 to -2.9). Difference in FACT-Hep Total Score: Dasatinib and mFOLFOX6 (n=44): -13.7 (-20.0 to -7.4).