Gefitinib and Capecitabine in Treating Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: gefitinib

Drug: capecitabine

Other: laboratory biomarker analysis

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00039390

U01CA099176 (U.S. NIH Grant/Contract)

NCI-2012-02467

UCHSC-01479

CDR0000069379 (Registry Identifier)

Details and patient eligibility

About

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

Full description

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.

Enrollment

41 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)