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

April 27, 2015 updated by: Orlando Health, Inc.

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

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.

Study Overview

Status

Withdrawn

Conditions

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.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Florida
      • Orlando, Florida, United States, 32806
        • UF Health Cancer Center at Orlando Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Approximately 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Approximately 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Omar R Kayaleh, M.D., Orlando Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (ANTICIPATED)

August 1, 2017

Study Completion (ANTICIPATED)

December 1, 2019

Study Registration Dates

First Submitted

June 5, 2014

First Submitted That Met QC Criteria

June 5, 2014

First Posted (ESTIMATE)

June 9, 2014

Study Record Updates

Last Update Posted (ESTIMATE)

April 28, 2015

Last Update Submitted That Met QC Criteria

April 27, 2015

Last Verified

April 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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