NCT02159248

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

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Orlando Health, Inc. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Pancreatic Cancer

Interventions

Type	Name	Description
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).

Timeline

• Start date: 2014-03-01
• Primary completion: 2017-08-01
• Completion: 2019-12-01
• First posted: 2014-06-09
• Last updated: 2015-04-28

Locations

1 site across 1 country: United States