Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

This study has been terminated.
(The protocol has been completed prematurely (e.g., due to poor accrual, insufficient drug supply, IND closure).)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00482625
First received: June 4, 2007
Last updated: April 18, 2014
Last verified: March 2014

June 4, 2007
April 18, 2014
June 2007
February 2010   (final data collection date for primary outcome measure)
Reduction in Number of Positive IPMN Celss and Staining Intensity After Treatment [ Time Frame: Pre-treatment and post-treatment ] [ Designated as safety issue: No ]
Number of participants showed a reduction in number of positive IPMN cells and staining intensity after treatment
Mucin 5AC protein expression measured by IHC
Complete list of historical versions of study NCT00482625 on ClinicalTrials.gov Archive Site
  • Plasma Calculated Concentration - OSI-774 (ng/mL) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Plasma concentration levels of Erlotinib (OSI-774)
  • Pancreas Calculated Concentration - OSI-774 (ng/g) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Pancreatic tissue concentration levels of Erlotinib (OSI-774)
  • Plasma Calculated Concentration - OSI-420 (ng/mL) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Plasma concentration levels of Erlotinib (OSI-420)
  • Pancreas Calculated Concentration - OSI-420 (ng/g) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
    Pancreatic tissue concentration levels of Erlotinib (OSI-420)
  • Number of Participants Reported at Least 1 Adverse Event With a Grade of 3 and Above [ 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 21-42 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
Armstrong WB, Wan XS, Kennedy AR, Taylor TH, Meyskens FL Jr. Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment. Laryngoscope. 2003 Oct;113(10):1687-702. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
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: Steven M Lipkin, MD,PhD Weill Cornell College of Medicine
National Cancer Institute (NCI)
March 2014

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