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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase Ib Multicenter Trial To Determine The Safety, Tolerance And Preliminary Antineoplastic Activity Of Gemcitabine Administered In Combination With Escalating Oral Doses Of OSI-774 To Patient Cohorts With Recently Diagnosed, Gemcitabine-Naive, Advanced Pancreatic Carcinoma Or Other Potentially Responsive Malignancies

Conditions
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Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: erlotinib hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: 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) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: 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 Renal: Creatinine less than 1.5 times ULN OR Creatinine clearance at least 60 mL/min Cardiovascular: 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 Gastrointestinal: No significant gastrointestinal abnormalities including: Requirement for IV alimentation Active peptic ulcer disease Ophthalmic: 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 Other: 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 PRIOR CONCURRENT THERAPY: Biologic therapy: 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 Chemotherapy: 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 Endocrine therapy: 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 Radiotherapy: 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 Surgery: See Disease Characteristics Recovered from any prior surgery No prior surgical procedures affecting absorption Other: No prior agent for the primary malignancy targeting the epidermal growth factor receptor (EGFR) or EGFR-specific tyrosine kinase activity

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: erlotinib hydrochloride|nan|
|Drug: gemcitabine hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer, unspecified adult solid tumor, protocol specific, stage IV pancreatic cancer