Gefitinib and Capecitabine in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of gefitinib and capecitabine in treating patients with advanced solid tumors. Biological therapies such as gefitinib may interfere with the growth of tumor cells and slow the growth of solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib and capecitabine may kill more tumor cells

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose of gefitinib and capecitabine in patients with advanced solid tumors. II. Determine the dose-limiting toxic effects of this regimen in these patients. III. Determine the pharmacologic profile of this regimen in these patients. OUTLINE: This is a dose-escalation study of gefitinib and capecitabine. Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 11-41 patients will be accrued for this study within 2.5 years.

Official Title
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A Phase I Trial of ZD1839 With Capecitabine in Patients With Advanced Solid Tumors (Formerly a Phase I Trial of ZD1839 With Capecitabine and Celecoxib)

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: capecitabine
* Drug: gefitinib
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed advanced solid tumor that is refractory to standard therapy or for which no standard therapy exists No uncontrolled brain metastases, including symptomatic lesions or lesions requiring treatment (e.g., glucocorticoids and/or anticonvulsants) Performance status - ECOG 0-2 At least 12 weeks WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Bilirubin no greater than 1.5 mg/dL AST and ALT no greater than 2.5 times upper limit of normal (5 times ULN if liver metastases present) Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min No active infections No other serious concurrent systemic disorders that would preclude study participation No other malignancy No prior hypersensitivity to sulfonamide-based drugs, nonsteroidal anti-inflammatory drugs, or fluorouracil No documented dihydropyrimidine dehydrogenase deficiency Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No concurrent immunotherapy At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No concurrent hormonal therapy At least 28 days since prior radiotherapy No concurrent radiotherapy At least 4 weeks since prior investigational agents No other concurrent experimental medications No concurrent drugs known to induce cytochrome P450 3A4 (e.g., rifampin, phenytoin, carbamazepine, or barbiturates)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (capecitabine, gefitinib)<br>Patients receive oral gefitinib once daily on days 1-14 and oral capecitabine twice daily on days 8-21. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gefitinib and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. | Drug: capecitabine<br>* Given orally (PO)<br>* Other names: Xeloda;Drug: gefitinib<br>* Given PO<br>* Other names: ZD 1839;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum-tolerated dose (MTD) defined as the those below that results in dose-limiting toxicity (DLT) in >= 2 of 6 new patients, as assessed by CTCAE version 3.0 |  | 28 days | 
| DTL defined as any grade 3 or greater non-hematological toxicity, and grade 3 or greater skin rash, grade 4 thrombocytopenia and/or neutropenia as assessed by CTCAE version 3.0 |  | 28 days | 
| Pharmacological profile |  | At baseline, at 30 minutes, at 1, 2, 3, and 4 hours of days 8, 14, and 21 (course 1) |