Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00482625
First received: June 4, 2007
Last updated: May 24, 2013
Last verified: February 2013
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Purpose
Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. This phase II trial is studying how well erlotinib hydrochloride works in treating patients with pancreatic cancer that can be removed by surgery
| Condition | Intervention | Phase |
|---|---|---|
|
Intraductal Papillary Mucinous Neoplasm of the Pancreas Recurrent Pancreatic Cancer Stage IA Pancreatic Cancer Stage IB Pancreatic Cancer Stage IIA Pancreatic Cancer Stage IIB Pancreatic Cancer Stage III Pancreatic Cancer |
Drug: erlotinib hydrochloride Procedure: conventional surgery Other: immunohistochemistry staining method Genetic: protein expression analysis Procedure: biopsy Other: pharmacological study Other: laboratory biomarker analysis |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase IIA Trial Testing Erlotinib as an Intervention Against Intraductal Pancreatic Mucinous Neoplasms |
Resource links provided by NLM:
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Greater than zero absolute mean decrease in MUC5AC expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]This measurement is a continuous variable. A single group univariate repeated measures analysis of variance will be used to detect differences over time in biomarker expression. Changes over time will be tested using univariate analysis of variance for repeated measures.
- Greater than zero absolute mean decrease in MUC5AC expression [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]This measurement is a continuous variable. A single group univariate repeated measures analysis of variance will be used to detect differences over time in biomarker expression. Changes over time will be tested using univariate analysis of variance for repeated measures.
Secondary Outcome Measures:
- Significant reductions in the expression of other IPMN EGF inducible biomarkers including pEGFR and pAKT [ Time Frame: Baseline ] [ Designated as safety issue: No ]Biomarker expression pre- and post-treatment will all be measured as continuous variables. Changes over time will be tested using univariate analysis of variance for repeated measures. The multiple secondary endpoints raise the issue of adjustment for multiple comparisons to maintain a type 1 error rate of 5%. Because this is a small study, use of the conservative Bonferroni adjustment may make it difficult to achieve statistical significance for secondary endpoints.
- Significant reductions in the expression of other IPMN EGF inducible biomarkers including pEGFR and pAKT [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]Biomarker expression pre- and post-treatment will all be measured as continuous variables. Changes over time will be tested using univariate analysis of variance for repeated measures. The multiple secondary endpoints raise the issue of adjustment for multiple comparisons to maintain a type 1 error rate of 5%. Because this is a small study, use of the conservative Bonferroni adjustment may make it difficult to achieve statistical significance for secondary endpoints.
- Toxicity evaluated using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 20 weeks ] [ Designated as safety issue: Yes ]The worst grade of pre-listed toxicity will be summarized by participant and by visit for each treatment group. Descriptive statistics (frequencies and percents) will be used to summarize data and hypotheses about group differences will be tested where appropriate.
| Enrollment: | 25 |
| Study Start Date: | June 2007 |
| Study Completion Date: | December 2012 |
| Primary Completion Date: | February 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO QD for 5-42 days. Patients then proceed to surgery.
|
Drug: erlotinib hydrochloride
Given PO
Other Names:
Procedure: conventional surgery
Undergo pancreatectomy
Other Name: surgery, conventional
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Genetic: protein expression analysis
Correlative studies
Procedure: biopsy
Correlative studies
Other Name: biopsies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To test the hypothesis that the activated epidermal growth factor receptor (EGFR) signal transduction biomarker Mucin 5AC (MUC5AC) protein expression within intraductal pancreatic mucinous neoplasm (IPMN) lesions will have greater than zero absolute mean decrease from baseline comparing pre and post 21-42 days of Erlotinib (erlotinib hydrochloride) administration at 100mg orally (PO) once daily (QD).
SECONDARY OBJECTIVES:
I. To test the hypothesis that other correlative IPMN EGF inducible biomarkers will have greater than zero absolute mean decrease from baseline pre and post Erlotinib 100mg PO QD therapy.
II. Safety of Erlotinib treatment. III. To determine Erlotinib pharmacokinetic concentration in plasma and pancreatic tissue at the 100mg/day dose up to 42 days of therapy.
OUTLINE:
Patients receive erlotinib hydrochloride PO QD for 21-42 days in the absence of disease progression or unacceptable toxicity. Patients then undergo to pancreatectomy.
After completion of study treatment, patients are followed up at 4-20 weeks.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Confirmed IPMN histological diagnosis, endoscopic ultrasound fine needle aspiration (EUS-FNA) core biopsy tissue specimen with plan for pancreatic surgical resection; histological diagnosis should be within 6 months of entry into protocol
- Patients must have adequate bone marrow function at study entry
- White blood cell (WBC) > 3,000
- Platelets > 100,000/mm^3
- Hemoglobin > 10 g/dL
- Plasma creatinine of < 1.6 mg/dL
- Total bilirubin < 1.5
- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x upper limit of normal
- Patients with evidence of obstructive lung disease (forced expiratory volume in one second [FEV1] < 80% predicted and FEV1/forced vital capacity [FVC] ratio < 90% of predicted value) as the etiology of a low diffusing capacity will still be eligible as long as the chest radiograph or computed tomography (CT) does not demonstrate interstitial changes
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Women of child-bearing potential and men taking study drug must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
- Ability to understand, as well as sign the written informed consent document
- If a woman of child-bearing potential, must have a negative pregnancy test prior to study entry; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Exclusion Criteria:
- Intake of EGFR antagonist, Erbitux (cetuximab)
- Previous history of sensitivity to Tarceva (erlotinib hydrochloride), Iressa (gefitinib), or Erbitux, such as a rash that is uncontrollable by topical steroids and/or antibiotics
- Uncontrollable diarrhea of any cause
- Active keratoconjunctivitis, or corneal surgery in the past three weeks
- Participants taking a known cytochrome P450 3A4 (CYP 3A4) inducer (e.g., phenytoin, carbamazepine, St. John's wort, and rifampin) and medications known to be inhibitors or metabolized by CYP3A4; these inhibitors include erythromycin, clarithromycin and ketoconazole, and patients taking them will be excluded since these drugs may be expected to result in altered exposure of Erlotinib
- Hospitalization within the past 5 years for mania or for bipolar disease
- Participants may not be receiving any other investigational pharmaceutical agents
- Women who are breast-feeding should not receive Erlotinib
- Any medical or psychosocial condition that, in the opinion of the investigator, could jeopardize the subject's participation in and compliance to the study
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00482625
Locations
| United States, California | |
| University of California Medical Center At Irvine-Orange Campus | |
| Orange, California, United States, 92868 | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | John Lee | Chao Family Comprehensive Cancer Center |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00482625 History of Changes |
| Other Study ID Numbers: | NCI-2009-00898, UCI 06-30, N01CN35160, CDR0000547235 |
| Study First Received: | June 4, 2007 |
| Last Updated: | May 24, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neoplasms Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases |
Endocrine System Diseases Erlotinib Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on June 18, 2013