Erlotinib, Gemcitabine, And Radiation Therapy In Treating Patients With Locally Advanced Unresectable Pancreatic Cancer

Study Overview

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

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.

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.

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

DRUG: erlotinib hydrochloride
DRUG: gemcitabine hydrochloride
RADIATION: radiation therapy
OTHER: laboratory biomarker analysis

NCI-2012-01439
03-031
NCI-5441
CDR0000305855
MSKCC-03031
U01CA069856 (U.S. NIH Grant/Contract)

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2003-07-08	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-06-03
First Submitted that Met QC Criteria 2003-07-08	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-06-04
First Posted (ESTIMATED) 2003-07-09	Results First Posted N/A	Last Verified 2013-06

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: erlotinib hydrochloride Given orally DRUG: gemcitabine hydrochloride Given IV RADIATION: radiation therapy Undergo radiotherapy OTHER: laboratory biomarker analysis Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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

DRUG: erlotinib hydrochloride

Given orally

DRUG: gemcitabine hydrochloride

Given IV

RADIATION: radiation therapy

Undergo radiotherapy

OTHER: laboratory biomarker analysis

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
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

Secondary Outcome Measures	Measure Description	Time Frame
Toxicity as assessed by CTCAE version 3.0		7.5 weeks
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
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
Overall survival		From the time of study enrollment until the date of death, assessed up to 6 years

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Eileen O'Reilly, Memorial Sloan Kettering Cancer Center

Publications

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

General Publications

No publications available

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Clinical Trial Record