NCT02154737

Gemcitabine and Pulse Dose Erlotinib in Second Line Treatment of Advanced Pancreatic Cancer

A Phase I, Open-label, Dose Escalation Study of Gemcitabine and Pulse Dose Erlotinib in Second Line Treatment of Advanced Pancreatic Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: Tony Reid, M.D., Ph.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to see whether an altered schedule of giving erlotinib in combination with gemcitabine will be safe and might improve the results of the treatment for advanced cancer of the pancreas. Gemcitabine and erlotinib are commercially available. Gemcitabine is FDA approved as first-line treatment for patients with locally advanced, unresectable or metastatic cancer of the pancreas. Erlotinib is FDA approved in combination with gemcitabine for the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer. The FDA recommended dose for erlotinib is 100 mg daily. This study will investigate the experimental administration of higher doses of erlotinib given for only three days twice a month, a schedule called "pulse dosing".

Detailed description

Survival of pancreatic cancer patients remains poor, and treatment with erlotinib remains one of the few agents that have demonstrated increased survival. Alternative dosing schedules for erlotinib should be explored since chronic low dose therapy fails to achieve therapeutically effective concentrations for many patients and leads to increased skin toxicity and may induce acquired resistance without significantly impacting the tumor. Therefore, higher doses given for shorter periods of exposure, similar to the dosing of most chemotherapeutic agents, may achieve more effective therapeutic doses of than chronic low dose therapy and may minimize skin toxicity observed with erlotinib. No phase I studies have been done with the combination of high dose pulse erlotinib therapy with gemcitabine. We propose a phase I dose escalation study of three day oral dosing of erlotinib with standard dose (1000 mg/m2) gemcitabine. The starting dose of erlotinib is 750 mg, approximately 50% of the the dose found to be safe in previous combination studies with carboplatin and paclitaxel and with pemetrexed \[Riely et al. 2009, Davies et al. 2009\]. Since acquired resistance can occur rapidly and 5 to 7 days of treatment is not better than 3 days of treatment, we will focus on a 3 day high-dose pulse treatment given every 14 days. This will provide 11 days between erlotinib dosing for the recovery of normal tissues. Levels of serum erlotinib will also be monitored due to considerable interpatient variability in the metabolism of erlotinib. The hypotheses of this study are: * High-dose pulse therapy with erlotinib can be safely administered with standard dose gemcitabine. * High-dose pulse therapy with erlotinib will permit recovery of the epidermis between treatments resulting in reduced skin toxicity compared to chronic daily dosing. * Disease control with high-dose pulse therapy may be superior to that with chronic low dose therapy.

Conditions

• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	Gemcitabine	Gemcitabine will be administered intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle.
DRUG	Erlotinib	Erlotinib will be administered orally on Days 2-4 and Days 16-18 of a 28-day cycle in serial cohorts with doses of 750mg, 1000mg, 1250mg, 1500mg, 1750mg, and 2000mg.

Timeline

• Start date: 2013-07-01
• Primary completion: 2020-09-03
• Completion: 2020-09-03
• First posted: 2014-06-03
• Last updated: 2021-03-02

Locations

1 site across 1 country: United States