Erlotinib, Combination Chemotherapy, and Radiation Therapy in Treating Patients With Stage I or Stage II Pancreatic Cancer That Can Be Removed By Surgery - Full Text View

Sponsors and Collaborators:	Sidney Kimmel Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00313560

Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Drugs used in chemotherapy, such as capecitabine and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with combination chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying how well giving erlotinib before and after surgery together with combination chemotherapy and radiation therapy works in treating patients with stage I or stage II pancreatic cancer that can be removed by surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: erlotinib hydrochloride Drug: placebo	Phase II

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Erlotinib Erlotinib hydrochloride Pancrelipase Ultrase

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Placebo Control
Official Title:	Phase II Study of Erlotinib (Tarceva) Combined With Chemoradiation and Adjuvant Chemotherapy in Patients With Resectable Pancreatic Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pharmacodynamics of neoadjuvant erlotinib [ Designated as safety issue: No ]
Antitumor activity of adjuvant therapy (erlotinib hydrochloride, capecitabine, gemcitabine hydrochloride, and radiotherapy) following surgical resection [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity profile of adjuvant therapy [ Designated as safety issue: Yes ]
Pharmacodynamic effects of adjuvant erlotinib hydrochloride on normal tissue [ Designated as safety issue: No ]
Pharmacokinetics of erlotinib hydrochloride and capecitabine [ Designated as safety issue: No ]
Allelic variants in candidate genes (EGFR, TS, DPD, MTHFR, and ORM1) as related to drug disposition and toxicity [ Designated as safety issue: Yes ]
Correlate pharmacodynamics and patient outcomes [ Designated as safety issue: No ]
Predicted response by positron-emission tomography (PET)/CT scan [ Designated as safety issue: No ]
Benefit of fusing PET/CT scans together with the radiotherapy planning CT scan [ Designated as safety issue: No ]
Decreased respiratory motion during radiation treatment and better radiation coverage by using the Active Breathing Coordinator [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	January 2006
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive oral erlotinib hydrochloride once a day for 3-5 days. Patients then proceed to surgery.	Drug: erlotinib hydrochloride Given orally
Arm II: Placebo Comparator Patients receive oral placebo once a day for 3-5 days. Patients then proceed to surgery.	Drug: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

Determine the pharmacodynamic (inhibition of epidermal growth factor receptor [EGFR] activation and signaling) effects of neoadjuvant erlotinib hydrochloride on tumor tissue of patients with resectable stage I or II pancreatic adenocarcinoma.
Determine, preliminarily, antitumor activity (progression-free survival) of adjuvant erlotinib hydrochloride in combination with standard chemoradiotherapy comprising capecitabine, gemcitabine hydrochloride, and radiotherapy after surgical resection in these patients.

Secondary

Characterize the toxicity profile of adjuvant erlotinib hydrochloride in combination with standard chemoradiotherapy in these patients.
Determine the pharmacodynamic (inhibition of EGFR activation and signaling) effects of erlotinib hydrochloride on normal tissue (skin and oral mucosa) of patients receiving erlotinib hydrochloride as adjuvant therapy.
Characterize the pharmacokinetics of erlotinib hydrochloride (assessing both total and unbound levels) given in combination with capecitabine and evaluate the association of common allelic variants in candidate genes (EGFR, TS, DPD, MTHFR, and ORM1) with drug disposition and toxicity.
Determine the relationships between pharmacodynamic effects and patient outcome.
Assess the value of PET/CT scanning as a predictor of response to erlotinib hydrochloride treatment in patients with pancreatic cancer.
Evaluate the benefit of fusing PET/CT scans together with the radiation treatment planning CT scan.
Determine if the Active Breathing Coordinator (ABC) minimizes the effects of respiratory motion during radiation treatment and results in better radiation coverage of the tumor bed and adjacent lymph nodes.

OUTLINE: This is a randomized, placebo-controlled study.

Neoadjuvant therapy: Patients are randomized to 1 of 2 neoadjuvant treatment arms.
- Arm I: Patients receive oral erlotinib hydrochloride once a day for 3-5 days. Patients then proceed to surgery.
- Arm II: Patients receive oral placebo once a day for 3-5 days. Patients then proceed to surgery.
Surgery: Patients undergo surgical resection. Patients then proceed to adjuvant therapy.
Adjuvant therapy: Patients receive oral capecitabine twice a day and oral erlotinib hydrochloride once a day for 5½ weeks. Patients also undergo concurrent radiotherapy 5 days a week for 5½ weeks. Beginning 6 weeks later, patients receive gemcitabine hydrochloride IV on days 1, 8, and 15 and oral erlotinib hydrochloride once daily on days 1-28. Treatment with gemcitabine hydrochloride and erlotinib hydrochloride repeats every 28 days for 4 courses.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of adenocarcinoma of the pancreas
- Stage I or II disease
- Previously untreated disease
Scheduled to undergo surgical resection at The Johns Hopkins Hospital
Candidate for postoperative adjuvant chemoradiation

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
WBC ≥ 3,000/mm^3
AST and ALT < 5 times upper limit of normal (ULN)
Bilirubin < 2.0 mg/dL
Creatinine < 2.0 mg/dL
aPTT < 40 seconds
PT < 2 seconds more than ULN
Not pregnant or nursing
Fertile patients must use effective contraception
Patients with high glucose levels ( > 140 mg/dL) are eligible but may not undergo PET scanning during the first part of the study
No hypersensitivity to capecitabine, doxifluridine, or fluorouracil
No known severe hypersensitivity to erlotinib hydrochloride or any of the excipients of this product
No other coexisting malignancies or malignancies diagnosed within the last 5 years, except basal cell carcinoma or cervical cancer in situ
No ongoing or active infection
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No psychiatric illness or social situations that would limit compliance with study requirements
No other uncontrolled illness
No gastrointestinal tract disease resulting in an inability to take oral medication
No known AIDS
No evidence of clinically active interstitial lung disease
- Patients with chronic stable radiographic changes who are asymptomatic are eligible

PRIOR CONCURRENT THERAPY:

Recovered from previous oncologic or other major surgery
No previous radiation to the abdomen
No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St John's wort)
No concurrent antiretroviral therapy for HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313560

Locations

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce 410-955-8804 jhcccro@jhmi.edu

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Manuel Hidalgo, MD, PhD

Sidney Kimmel Comprehensive Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000465208, JHOC-J0534, JHOC-05080408
Study First Received:	April 11, 2006
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00313560
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer

Study placed in the following topic categories:

Erlotinib
Digestive System Diseases
Digestive System Neoplasms
Pancreatic Neoplasms
Endocrine System Diseases
Pancreatic Diseases

Gastrointestinal Neoplasms
Endocrinopathy
Adenocarcinoma
Pancrelipase
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action

Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009