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

NCT ID: NCT01652976

Last Updated: 2021-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2020-07-31

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.

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.

Conditions

Pancreatic Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Dasatinib and mFOLFOX6

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle

mFOLFOX6

Intervention Type: DRUG

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

Interventions

Dasatinib

Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Sprycel; Oxaliplatin; Leucovorin; 5-Fluorouracil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas J George, Jr., MD, FACP

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health Cancer Center

Gainesville, Florida, United States

Countries

United States

References

George TJ Jr, Trevino JG, Liu C. Src inhibition is still a relevant target in pancreatic cancer. Oncologist. 2014 Feb;19(2):211. doi: 10.1634/theoncologist.2013-0410. Epub 2014 Jan 23. No abstract available.

Reference Type: DERIVED

PMID: 24457377 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CA180-359

Identifier Type: OTHER

Identifier Source: secondary_id

OCR11303

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201600540

Identifier Type: -

Identifier Source: org_study_id