Gefitinib and Capecitabine in Treating Patients With Advanced Solid Tumors

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)

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

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: gefitinib; Drug: capecitabine

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (capecitabine, gefitinib); 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.

Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: gefitinib; Given PO; Other Names: Iressa; ZD 1839; Drug: capecitabine; Given orally (PO); Other Names: Xeloda; CAPE; Ro 09-1978/000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michele Basche, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: June 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 25, 2013
• Last Update Submitted That Met QC Criteria: January 24, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Capecitabine; Gefitinib
• Other Study ID Numbers: NCI-2012-02467; UCHSC-01479; U01CA099176 (U.S. NIH Grant/Contract); CDR0000069379 (Registry Identifier: PDQ (Physician Data Query))