Erlotinib, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Unresectable Pancreatic Cancer
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
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 |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A PHASE 1 STUDY OF OSI-774 IN COMBINATION WITH GEMCITABINE AND RADIATION IN LOCALLY ADVANCED, NON-OPERABLE PANCREATIC CANCER |
- 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 ] [ Designated as safety issue: Yes ]
- Toxicity as assessed by CTCAE version 3.0 [ Time Frame: 7.5 weeks ] [ Designated as safety issue: Yes ]
- Response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]Kaplan-Meier methods will be utilized to estimate the response duration.
- Progression-free survival as assessed by RECIST [ Time Frame: From the time of study enrollment until progression of disease is documented, assessed up to 6 years ] [ Designated as safety issue: No ]Kaplan-Meier methods will be utilized to estimate the progression-free survival.
- Overall survival [ Time Frame: From the time of study enrollment until the date of death, assessed up to 6 years ] [ Designated as safety issue: No ]
| Enrollment: | 28 |
| Study Start Date: | June 2003 |
| Primary Completion Date: | January 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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 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.
|
Drug: erlotinib hydrochloride
Given orally
Other Names:
Drug: gemcitabine hydrochloride
Given IV
Other Names:
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, New York | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Principal Investigator: | Eileen O'Reilly | Memorial Sloan-Kettering Cancer Center |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00063947 History of Changes |
| Other Study ID Numbers: | NCI-2012-01439, 03-031, U01CA069856, CDR0000305855 |
| Study First Received: | July 8, 2003 |
| Last Updated: | December 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Adenocarcinoma Adenocarcinoma, Mucinous Pancreatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine |
Erlotinib Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Radiation-Sensitizing Agents Protein Kinase Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013