A Phase I Study of OSI-774 in Combination With Gemcitabine and Radiation in Locally Advanced, Non-Operable Pancreatic Cancer
Overview
- Phase
- Phase 1
- Intervention
- erlotinib hydrochloride
- Conditions
- Adenocarcinoma of the Pancreas
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Maximum-tolerated dose (MTD) of erlotinib hydrochloride based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
This phase I trial is studying the side effects and best dose of erlotinib when given together with gemcitabine and radiation therapy in treating patients with locally advanced unresectable pancreatic cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with gemcitabine may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose of erlotinib given concurrently with gemcitabine and radiotherapy in patients with locally advanced unresectable pancreatic cancer. SECONDARY OBJECTIVES: I. Determine the toxicity of this regimen in these patients. II. Determine, preliminarily, the antitumor efficacy of this regimen, in terms of response rate, in these patients. III. Determine the time to tumor progression and overall survival of patients treated with this regimen. OUTLINE: This is a non-randomized, open-label, dose-escalation study of erlotinib. Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 10 patients receive treatment at that dose. Patients are radiologically restaged 3-4 weeks after completion of radiotherapy. Patients with stable or responsive disease proceed to maintenance therapy. Patients whose imaging studies suggest a potential for curative resection are referred for a surgical evaluation before initiating maintenance therapy. Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 19-28 patients will be accrued for this study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas
- •Locally advanced, unresectable disease, defined by all of the following:
- •Obvious encasement of the celiac, hepatic, or superior mesenteric artery
- •Encasement of the portal or superior mesenteric vein not amenable to surgical resection
- •Extrapancreatic extension with or without regional lymph node involvement
- •No evidence of distant metastatic disease by staging laparoscopy\*
- •Locally recurrent disease after prior curative surgery allowed provided the following are true:
- •No prior chemotherapy or radiotherapy
- •No evidence of distant metastatic disease by staging laparoscopy\*
- •No islet cell pancreatic cancer or lymphoma or sarcoma of the pancreas
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (radiotherapy, gemcitabine, erlotinib hydrochloride)
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease proceed to maintenance therapy. Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: erlotinib hydrochloride
Treatment (radiotherapy, gemcitabine, erlotinib hydrochloride)
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease proceed to maintenance therapy. Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: gemcitabine hydrochloride
Treatment (radiotherapy, gemcitabine, erlotinib hydrochloride)
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease proceed to maintenance therapy. Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: radiation therapy
Treatment (radiotherapy, gemcitabine, erlotinib hydrochloride)
Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5.5 weeks. Beginning on day 1 and continuing concurrently with radiotherapy, patients receive gemcitabine IV over 30 minutes twice weekly and oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responsive disease proceed to maintenance therapy. Maintenance therapy: Beginning 4-7 weeks after the completion of chemoradiotherapy, patients receive maintenance chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and oral erlotinib once daily. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Maximum-tolerated dose (MTD) of erlotinib hydrochloride based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Time Frame: 7.5 weeks
Secondary Outcomes
- Toxicity as assessed by CTCAE version 3.0(7.5 weeks)
- Response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)(Up to 6 years)
- Progression-free survival as assessed by RECIST(From the time of study enrollment until progression of disease is documented, assessed up to 6 years)
- Overall survival(From the time of study enrollment until the date of death, assessed up to 6 years)