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

NCT01652976 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB201600540CA180-359OCR11303
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer Metastatic

Keywords

Metastatic; Pancreatic Cancer; Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  3 years

Secondary Outcomes (10)

• Response Rate

  3 years

• Freedom From Metastasis

  3 years

• Median Time To Progression

  3 years

• Median Overall Survival

  4 years

• Clinical Benefit Rate

  3 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Dasatinib and mFOLFOX6

Drug: Dasatinib; Drug: mFOLFOX6

Interventions

Dasatinib DRUG

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

Also known as: Sprycel

Treatment Arm

mFOLFOX6 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

Also known as: Oxaliplatin, Leucovorin, 5-Fluorouracil

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Florida: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UF Health Cancer Center

Gainesville, Florida, 32610, United States

Location

Related Publications (1)

• 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.

  PMID: 24457377 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Pancreatic Neoplasms; Adenocarcinoma

Interventions

Dasatinib; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones

Results Point of Contact

• Title: Allison Allegra
• Organization: University of Florida

allisonallegra3@ufl.edu

352-294-5691

Study Officials

• Thomas J George, Jr., MD, FACP

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: July 30, 2012
• Study Start: July 1, 2012
• Primary Completion: February 1, 2018
• Study Completion: July 1, 2020
• Last Updated: January 5, 2021
• Results First Posted: June 13, 2019

Record last verified: 2020-12

Locations

US (1)