Phase II Study of 5-FU, Oxaliplatin Plus Dasatinib in Metastatic Pancreatic Adenocarcinoma (FOLFOX-D)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Florida
Sponsor:
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT01652976
First received: July 23, 2012
Last updated: June 19, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Pancreatic Cancer Metastatic
Drug: Dasatinib
Drug: mFOLFOX6
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of 5-Fluorouracil, Oxaliplatin Plus Dasatinib (FOLFOX-D) in First-line Metastatic Pancreatic Adenocarcinoma

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Dasatinib activity [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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:
  • Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the response rate (RR) by RECIST criteria

  • Freedom From Metastasis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the rate of freedom from metastasis (FFM)

  • Time To Progression [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the time to progression (TTP)

  • Overall Survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    To determine overall survival (OS)

  • Clinical Benefit Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the clinical benefit rate (CBR)

  • Site of Failure [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the site of failure of this regimen in this population

  • Safety and Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To determine the safety profile and tolerability of this regimen in this population by evaluating acute treatment related toxicities

  • Drug Compliance [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine patient compliance with oral therapy

  • Quality of Life [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    To determine the quality of life (QOL) of patients receiving this therapy

  • Correlative Specimen Analysis [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Exploratory tissue and serum correlative analyses to identify predictors of response


Estimated Enrollment: 42
Study Start Date: July 2012
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Dasatinib and mFOLFOX6
Drug: Dasatinib
Dasatinib 150mg PO daily on days 1-14 of each 14 day cycle
Other Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652976

Contacts
Contact: Alison Ivey, RN 352-265-0680 ext 88411 aivey@ufl.edu
Contact: Kevin Tormes, RN 352-265-0680 ext 87617 ktormes@ufl.edu

Locations
United States, Florida
UF Health Cancer Center Recruiting
Gainesville, Florida, United States, 32610
UF Health Cancer Center at Orlando Health Not yet recruiting
Orlando, Florida, United States, 32806
Sponsors and Collaborators
University of Florida
Investigators
Principal Investigator: Thomas J George, Jr., MD, FACP University of Florida
  More Information

No publications provided by University of Florida

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT01652976     History of Changes
Other Study ID Numbers: CA180-359
Study First Received: July 23, 2012
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
Metastatic
Pancreatic Cancer
Adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorouracil
Oxaliplatin
Leucovorin
Dasatinib
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014