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
Conditions
Brief summary
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
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.
Interventions
DRUGerlotinib hydrochloride
Given PO
PROCEDUREconventional surgery
Undergo pancreatectomy
OTHERimmunohistochemistry staining method
Correlative studies
GENETICprotein expression analysis
Correlative studies
PROCEDUREbiopsy
Correlative studies
OTHERpharmacological study
Correlative studies
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Number of Positive IPMN Celss and Staining Intensity After Treatment | Pre-treatment and post-treatment | Number of participants showed a reduction in number of positive IPMN cells and staining intensity after treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pancreas Calculated Concentration - OSI-420 (ng/g) | 20 weeks | Pancreatic tissue concentration levels of Erlotinib (OSI-420) |
| Plasma Calculated Concentration - OSI-774 (ng/mL) | 20 weeks | Plasma concentration levels of Erlotinib (OSI-774) |
| Pancreas Calculated Concentration - OSI-774 (ng/g) | 20 weeks | Pancreatic tissue concentration levels of Erlotinib (OSI-774) |
| Plasma Calculated Concentration - OSI-420 (ng/mL) | 20 weeks | Plasma concentration levels of Erlotinib (OSI-420) |
| Number of Participants Reported at Least 1 Adverse Event With a Grade of 3 and Above | Up to 20 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Enzyme Inhibitor Therapy) Patients receive erlotinib hydrochloride PO QD for 21-42 days. Patients then proceed to surgery.
erlotinib hydrochloride: Given PO
conventional surgery: Undergo pancreatectomy
immunohistochemistry staining method: Correlative studies
protein expression analysis: Correlative studies
biopsy: Correlative studies
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Treatment (Enzyme Inhibitor Therapy) |
|---|---|
| Age, Continuous | 61.17 years STANDARD_DEVIATION 14.48 |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Reduction in Number of Positive IPMN Celss and Staining Intensity After Treatment
Number of participants showed a reduction in number of positive IPMN cells and staining intensity after treatment
Time frame: Pre-treatment and post-treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Reduction in Number of Positive IPMN Celss and Staining Intensity After Treatment | 2 participants |
Secondary
Number of Participants Reported at Least 1 Adverse Event With a Grade of 3 and Above
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.
Time frame: Up to 20 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Number of Participants Reported at Least 1 Adverse Event With a Grade of 3 and Above | 0 participants |
Secondary
Pancreas Calculated Concentration - OSI-420 (ng/g)
Pancreatic tissue concentration levels of Erlotinib (OSI-420)
Time frame: 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Pancreas Calculated Concentration - OSI-420 (ng/g) | 17.3 ng/g | Standard Deviation 7.2 |
Secondary
Pancreas Calculated Concentration - OSI-774 (ng/g)
Pancreatic tissue concentration levels of Erlotinib (OSI-774)
Time frame: 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Pancreas Calculated Concentration - OSI-774 (ng/g) | 188.7 ng/g | Standard Deviation 121.7 |
Secondary
Plasma Calculated Concentration - OSI-420 (ng/mL)
Plasma concentration levels of Erlotinib (OSI-420)
Time frame: 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Plasma Calculated Concentration - OSI-420 (ng/mL) | 27.6 ng/mL | Standard Deviation 21.3 |
Secondary
Plasma Calculated Concentration - OSI-774 (ng/mL)
Plasma concentration levels of Erlotinib (OSI-774)
Time frame: 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | Plasma Calculated Concentration - OSI-774 (ng/mL) | 428.5 ng/mL | Standard Deviation 290.4 |