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Tolfenamic Acid, Gemcitabine and Radiation for Locally Advanced or Metastatic Pancreatic Cancer Requiring Radiation

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ClinicalTrials.gov Identifier: NCT02159248
Recruitment Status : Withdrawn (The study closed prior to enrolling any participants.)
First Posted : June 9, 2014
Last Update Posted : April 28, 2015
Sponsor:
Information provided by (Responsible Party):
Orlando Health, Inc.

Brief Summary:

The purposes of this study are to:

  • Evaluate the safety and toxicity of tolfenamic acid when used with gemcitabine and radiation therapy in patients with locally advanced or metastatic pancreatic cancer.
  • Determine the maximum-tolerated dose (MTD) of tolfenamic acid when used with gemcitabine and radiation in pancreatic cancer.
  • Characterize the pharmacokinetic profile of tolfenamic acid when used with gemcitabine and radiation.
  • Assess the anti-tumor response to tolfenamic acid when used with gemcitabine and radiation in patients with advanced pancreatic malignancies.

Condition or disease Intervention/treatment Phase
Pancreatic Cancer Drug: Tolfenamic acid + gemcitabine + radiation Phase 1

Detailed Description:

This is a phase I, open-label, non-randomized, single-center, dose-escalation study which utilizes tolfenamic acid in combination with gemcitabine and radiation in patients with locally advanced or metastatic pancreatic malignancies which require definitive or palliative radiation.

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to have a variety of anti-neoplastic mechanisms, including inhibition of cell growth, promotion of apoptosis and inhibition of angiogenesis. Tolfenamic acid is an oral (NSAID) migraine medication which has demonstrated anti-tumor activity in preclinical pancreatic models when used with Gem/XRT (gemcitabine and radiation therapy) and as a single agent.

Each patient enrolled will receive tolfenamic acid in combination with Gem/XRT. Depending on cohort assignment, patients will self-administer tolfenamic acid at either 200mg, 400mg, 600mg or 800mg three times per day. Gemcitabine will be administered intravenously at 400 mg/m2, every seven days for a maximum of 5 doses, starting with the second week of tolfenamic acid administration. Radiation will be given 5 days per week (Monday-Friday) for up to 5 ½ weeks for a maximum dose of 50.4 Gy, beginning with the second week of tolfenamic acid administration.

A maximum of 24 patients will be enrolled in the dose escalation portion of the study. After the maximum tolerated dose (MTD) of tolfenamic acid has been determined, patients will be enrolled in an expansion cohort (at the MTD or the highest dose level achieved if the MTD is not reached) to further assess safety and the anti-tumor response to treatment with tolfenamic acid plus Gem/XRT.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 09.017 - A Phase I Study of Tolfenamic Acid With Gemcitabine and Radiation in Patients With Locally Advanced or Metastatic Pancreatic Cancer Requiring Definitive or Palliative Radiation Therapy
Study Start Date : March 2014
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tolfenamic acid + gemcitabine + radiation Drug: Tolfenamic acid + gemcitabine + radiation

Cohort 1: 200mg of oral tolfenamic acid, three times per day for 6 1/2 weeks, in combination with weekly intravenous gemcitabine at 400mg/m2 for 5 doses and external beam radiation for 5 1/2 weeks (28 doses at 1.8 Gy/Fx/day).

Cohort 2: 400mg of oral tolfenamic acid, three times per day for 6 1/2 weeks, in combination with weekly intravenous gemcitabine at 400mg/m2 for 5 doses and external beam radiation for 5 1/2 weeks (28 doses at 1.8 Gy/Fx/day).

Cohort 3: 600mg of oral tolfenamic acid, three times per day for 6 1/2 weeks, in combination with weekly intravenous gemcitabine at 400mg/m2 for 5 doses and external beam radiation for 5 1/2 weeks (28 doses at 1.8 Gy/Fx/day).

Cohort 4: 800mg of oral tolfenamic acid, three times per day for 6 1/2 weeks, in combination with weekly intravenous gemcitabine at 400mg/m2 for 5 doses and external beam radiation for 5 1/2 weeks (28 doses at 1.8 Gy/Fx/day).





Primary Outcome Measures :
  1. Evaluate safety and toxicity [ Time Frame: Approximately 16 weeks ]
    Evaluate the safety and toxicity of escalating doses of tolfenamic acid when used with gemcitabine and radiation in patients with advanced pancreatic malignancies.


Secondary Outcome Measures :
  1. Assess the anti-tumor response. [ Time Frame: Approximately 16 weeks ]
    Assess the anti-tumor response to tolfenamic acid when used with gemcitabine and radiation in patients with locally advanced or metastatic pancreatic malignancies.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Primary Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed:

    1. Locally advanced (potentially resectable) pancreatic adenocarcinoma requiring neoadjuvant radiation or
    2. Locally advanced (nonresectable) or metastatic pancreatic adenocarcinoma requiring definitive or palliative radiation therapy
  2. Patients may have either measurable or non-measurable disease (according to RECIST criteria, Version 1.1).
  3. Age ≥ 18 years
  4. ECOG performance status of 0 or 1.
  5. A life expectancy of at least 12 weeks.
  6. No other concurrent radiotherapy, chemotherapy or immunotherapy.
  7. A minimum of 4 weeks must have elapsed since completion of any prior chemotherapy or immunotherapy.
  8. Patient must have:

    1. Absolute neutrophil count (ANC) ≥1,000/mm3
    2. Platelets ≥100,000/mm3
    3. Hemoglobin ≥10 g/dL [Transfusion to meet the hemoglobin requirement is acceptable]
    4. Serum creatinine ≤ 1.5 X ULN
    5. Total bilirubin ≤ 1.5 X ULN
    6. Aspartate aminotransferase (AST) ≤ 2.5 X ULN
    7. Alanine aminotransferase (ALT) ≤ 2.5 X ULN
    8. Alkaline phosphatase ≤ 2.5 X ULN
    9. PT/INR ≤ 1.5 X ULN
    10. aPTT ≤ 1.5 X ULN
    11. Urine Protein ≤ Grade 1
  9. For patients on warfarin: Must have maintained a stable INR on a stable dose of warfarin for at least 4 weeks prior to start of treatment.

Primary Exclusion Criteria:

  1. Patients who have received prior radiation for their current malignancy at the location of interest.
  2. Patients who have not recovered (to Grade 1 or less) from adverse events, other than alopecia and neuropathy, caused by previously administered chemotherapeutic agents, at the discretion of the PI/treating physician.
  3. Tolfenamic acid use concurrent with, or within 8 weeks prior to the diagnosis of pancreatic cancer.
  4. Current use of any non-steroidal anti-inflammatory agents (NSAIDs), including aspirin, (other than tolfenamic acid) within 4 weeks prior to the start of active treatment.
  5. Previous history of hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other NSAIDs.
  6. History of recurrent peptic ulcer/hemorrhage (two or more distinct episodes).
  7. History of gastrointestinal bleeding or perforation related to previous use of NSAIDS.
  8. New York Heart Association Functional Classification of 3 or 4.
  9. Known autoimmune disease that could preclude the use of radiation, at the discretion of the treating physician.
  10. History or evidence of CNS disease (e.g., any brain metastases, primary brain tumor, seizures not controlled with standard medical therapy, or history of stroke).
  11. Known HIV positive.
  12. Active systemic infection requiring parenteral antibiotic therapy.
  13. Receiving systemic steroid therapy. (Inhaled steroid therapy is allowable.)
  14. History of other malignancies within the last 5 years with the exception of non- melanoma skin cancer or cervical cancer in situ that has been successfully treated.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159248


Locations
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United States, Florida
UF Health Cancer Center at Orlando Health
Orlando, Florida, United States, 32806
Sponsors and Collaborators
Orlando Health, Inc.
Investigators
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Principal Investigator: Omar R Kayaleh, M.D. Orlando Health

Publications:

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Responsible Party: Orlando Health, Inc.
ClinicalTrials.gov Identifier: NCT02159248     History of Changes
Other Study ID Numbers: 09.017
First Posted: June 9, 2014    Key Record Dates
Last Update Posted: April 28, 2015
Last Verified: April 2015
Keywords provided by Orlando Health, Inc.:
pancreatic, gemcitabine, radiation, tolfenamic acid
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Gemcitabine
Tolfenamic acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents