Erlotinib, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Unresectable Pancreatic Cancer

Stage III Pancreatic Cancer Clinical Trial

Official title:

A Phase I Study of OSI-774 in Combination With Gemcitabine and Radiation in Locally Advanced, Non-Operable Pancreatic Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00063947
• Other study ID #: NCI-2012-01439
• Secondary ID: 03-031NCI-5441CD
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2003
• Last updated: June 3, 2013
• Start date: May 2003

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• Measurable or evaluable disease

• Primary pancreatic tumor is considered evaluable and not measurable disease

• Lymph node mass considered measurable disease

• No known brain metastases

• Performance status - ECOG 0-2

• More than 12 weeks

• WBC = 3,000/mm^3

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Bilirubin = 1.5 mg/dL

• AST and ALT = 2.5 times upper limit of normal

• Creatinine = 2.0 mg/dL

• Creatinine clearance = 60 mL/min

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No abnormalities of the cornea based on history (e.g., dry eye syndrome or Sjögren's syndrome)

• No congenital abnormality (e.g., Fuch's dystrophy)

• No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)

• No abnormal corneal sensitivity test (Schirmer test or similar tear production test)

• No Crohn's disease or inflammatory bowel disease that would preclude undergoing external beam radiotherapy

• Able to tolerate oral medication

• No requirement for IV alimentation

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No ongoing or active infection

• No other concurrent uncontrolled illness

• No psychiatric illness or social situation that would preclude study compliance

• See Disease Characteristics

• No prior gemcitabine

• See Disease Characteristics

• See Disease Characteristics

• No prior epidermal growth factor receptor-targeting therapy

• No prior therapy for pancreatic cancer (except surgery)

• No concurrent commercial or other investigational agents or therapies intended to treat the malignancy

• No concurrent combination antiretroviral therapy for HIV-positive patients

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Recurrent Pancreatic Cancer
• Stage II Pancreatic Cancer
• Stage III Pancreatic Cancer

Intervention

Drug:
• erlotinib hydrochloride
Given orally
• gemcitabine hydrochloride
Given IV

Radiation:
• radiation therapy
Undergo radiotherapy

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		7.5 weeks	Yes
Secondary	Toxicity as assessed by CTCAE version 3.0		7.5 weeks	Yes
Secondary	Response rate according to Response Evaluation Criteria in Solid Tumors (RECIST)	Kaplan-Meier methods will be utilized to estimate the response duration.	Up to 6 years	No
Secondary	Progression-free survival as assessed by RECIST	Kaplan-Meier methods will be utilized to estimate the progression-free survival.	From the time of study enrollment until progression of disease is documented, assessed up to 6 years	No
Secondary	Overall survival		From the time of study enrollment until the date of death, assessed up to 6 years	No