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
  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:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 6
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 21-42 days. Patients then proceed to surgery.
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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Steven M Lipkin, MD,PhD Weill Cornell College of Medicine
  More Information

Publications:
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
Results First Received: April 18, 2014
Last Updated: April 18, 2014
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 August 27, 2014