Erlotinib Combined With Gemcitabine In Treating Patients With Newly Diagnosed Locally Advanced Or Metastatic Pancreatic Cancer Or Other Solid Tumors

Study Overview

Erlotinib Combined With Gemcitabine in Treating Patients With Newly Diagnosed Locally Advanced or Metastatic Pancreatic Cancer or Other Solid Tumors

RATIONALE: Erlotinib may interfere with the growth of tumor cells and slow the growth of the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib with gemcitabine may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with gemcitabine in treating patients who have newly diagnosed locally advanced or metastatic pancreatic cancer or other solid tumors.

OBJECTIVES: * Determine the maximum tolerated dose of erlotinib in combination with gemcitabine in patients with recently diagnosed, gemcitabine-naive, locally advanced or metastatic pancreatic carcinoma or other potentially responsive solid tumor. * Determine the safety and tolerability of this regimen in these patients. * Determine the pharmacokinetics of this regimen in these patients. * Determine the objective antitumor response rate and response duration in patients treated with this regimen. * Determine the time to disease progression and duration of overall survival in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of erlotinib. Patients receive gemcitabine IV over 30 minutes on day 1 of weeks 1-7 and oral erlotinib once daily beginning on day 3 of week 1 and continuing for 8 weeks (course 1). Patients receive subsequent courses of therapy comprising gemcitabine once weekly for 3 weeks and erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are accrued and treated at the MTD as above. Patients are followed at 30 days. PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 3 months.

Pancreatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific

DRUG: erlotinib hydrochloride
DRUG: gemcitabine hydrochloride

OSI-774-155
CDR0000069266
UARIZ-HSC-01128
NCI-V02-1694

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2002-04-09	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2018-01-08
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2018-01-10
First Posted (ACTUAL) 2003-01-27	Results First Posted N/A	Last Verified 2015-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
N/A

Interventional Model:
N/A

Masking:
N/A

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically or cytologically confirmed locally advanced or metastatic epithelial carcinoma of the pancreas or other malignancy considered to be potentially responsive to gemcitabine

Newly diagnosed or gemcitabine naive
Measurable or evaluable disease
Not amenable to surgical intervention due to medical contraindications or non-resectability of the tumor
No islet cell tumors or other non-epithelial cell carcinomas of the pancreas
No active CNS metastases or leptomeningeal disease

Treated or asymptomatic brain metastases are allowed if on a stable dose of corticosteroids and/or there is no change in brain disease status for at least 4 weeks after related therapy (e.g., whole-brain radiotherapy)

18 and over

Karnofsky 70-100%

Not specified

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Bilirubin no greater than 2.0 mg/dL (except for documented Gilbert's syndrome)
AST or ALT less than 2 times upper limit of normal (ULN) (no greater than 5 times ULN if hepatic obstruction or metastases present)
Albumin at least 2.5 g/dL

Creatinine less than 1.5 times ULN OR
Creatinine clearance at least 60 mL/min

No significant cardiovascular disease
No history of congestive heart failure currently requiring therapy
No ventricular arrhythmia requiring anti-arrhythmic therapy
No severe conduction disturbances
No angina pectoris requiring therapy
No myocardial infarction within the past 6 months

No significant gastrointestinal abnormalities including:

Requirement for IV alimentation
Active peptic ulcer disease

No significant ophthalmologic abnormalities including:

Severe dry eye syndrome
Keratoconjunctivitis sicca
Sjogren's syndrome
Severe exposure keratopathy
Disorders that would increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
Abnormal Schirmer test (less than 2 mm) allowed provided there is no evidence of clinically significant corneal surface abnormalities

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known or suspected hypersensitivity to gemcitabine
No uncontrolled infection
HIV negative
No other malignancy within the past 5 years except treated non-melanoma skin cancer or carcinoma in situ of the breast or cervix
No other life-threatening illness
No psychiatric disorders or altered mental status the would preclude informed consent or study

At least 28 days since prior immunotherapy or biological response modified therapy for the primary malignancy
No concurrent immunotherapy or biologic response modifier therapy for the primary malignancy

See Disease Characteristics
At least 28 days since prior chemotherapy for the primary malignancy
No prior mitomycin or nitrosoureas for the primary malignancy
No more than 6 prior courses of chemotherapy with an alkylating agent for the primary malignancy
No prior gemcitabine for the primary malignancy except as a low-dose (less than 500 mg/m^2) radiosensitizer administered concurrently with or within 2 weeks after radiotherapy at least 3 months ago
No other concurrent chemotherapy for the primary malignancy

See Disease Characteristics
At least 28 days since prior systemic hormonal therapy (except LH-RH agonists) for the primary malignancy
No concurrent systemic hormonal therapy (except LH-RH agonists) for the primary malignancy
Other concurrent endocrine therapy is allowed as follows:

Hormonal therapy (e.g., megestrol) for appetite stimulation
Nasal, ophthalmic, or topical glucocorticoids
Oral glucocorticoids for adrenal insufficiency
Low-dose maintenance steroids

See Disease Characteristics
At least 28 days since prior radiotherapy for the primary malignancy or metastases and recovered
No prior wide-field radiotherapy to 25% or more of marrow-bearing bone
No prior pelvic irradiation
No concurrent radiotherapy for the primary malignancy or metastases
No concurrent wide-field radiotherapy for pain management

See Disease Characteristics
Recovered from any prior surgery
No prior surgical procedures affecting absorption

No prior agent for the primary malignancy targeting the epidermal growth factor receptor (EGFR) or EGFR-specific tyrosine kinase activity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: Pedro Santabarbara, MD, OSI Pharmaceuticals

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Dragovich T, Patnaik A, Rowinsky EK, et al.: A phase I B trial of gemcitabine and erlotinib HCL in patients with advanced pancreatic adenocarcinoma and other potentially responsive malignancies. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-895, 2003.

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Clinical Trial Record