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

June 4, 2007
May 24, 2013
June 2007
February 2010   (final data collection date for primary outcome measure)
  • 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.
Mucin 5AC protein expression measured by IHC
Complete list of historical versions of study NCT00482625 on ClinicalTrials.gov Archive Site
  • 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.
  • Change in tissue markers (including phosphorylated EGFR and AKT) measured by IHC
  • Safety
  • Pharmacokinetics
Not Provided
Not Provided
 
Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery
Phase IIA Trial Testing Erlotinib as an Intervention Against Intraductal Pancreatic Mucinous Neoplasms

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

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given PO
    Other Names:
    • CP-358,774
    • erlotinib
    • OSI-774
  • 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
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive erlotinib hydrochloride PO QD for 5-42 days. Patients then proceed to surgery.
Interventions:
  • Drug: erlotinib hydrochloride
  • Procedure: conventional surgery
  • Other: immunohistochemistry staining method
  • Genetic: protein expression analysis
  • Procedure: biopsy
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
December 2012
February 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00482625
NCI-2009-00898, UCI 06-30, N01CN35160, CDR0000547235
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: John Lee Chao Family Comprehensive Cancer Center
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP