Etoposide and Celecoxib in Patients With Advanced Cancer

Phase I Trial of Oral Etoposide in Combination With Celecoxib in Patients With Advanced Malignancies

RATIONALE: Etoposide and celecoxib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving more than 1 drug may be an effective treatment for advanced cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of celecoxib when given together with etoposide in treating patients with advanced cancer.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: immunoenzyme technique; Drug: etoposide; Drug: celecoxib

Detailed Description

OBJECTIVES:

• To describe the toxicities of the combination of oral etoposide at 50 mg daily with escalating doses of celecoxib in patients with advanced malignancies.
• To evaluate the effects of the combination of etoposide and celecoxib on plasma levels of vascular endothelial growth factor.

OUTLINE: This is a dose-escalation study of celecoxib.

In course 1, patients receive oral etoposide once daily on days 1-35 and oral celecoxib twice daily on days 8-35. In all subsequent courses, patients receive oral etoposide once daily and oral celecoxib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, periodically during treatment, and at time of tumor progression. Samples are analyzed for vascular endothelial growth factor levels by enzyme-linked immunosorbent assay and stored for future analysis of circulating DNA of angiogenic biomarkers by polymerase chain reaction assays.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven diagnosis of a malignant disease for which no satisfactory treatment exists at the time of enrollment
• Patients with brain metastases which at the time of study enrollment are controlled and do not require treatment with corticosteroids are eligible

PATIENT CHARACTERISTICS:

Inclusion criteria:

• WHO performance status 0-2
• Life expectancy ≥ 3 months
• ANC > 1.5 x 10^9/L
• Platelet count > 100 x 10^9/L
• Creatinine clearance > 50 mL/min
• Serum bilirubin < 1.5 mg/dL
• AST and ALT < 2.0 times upper limit of normal (unless clearly due to the presence of tumor)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Patient must be capable of understanding the nature of the trial and must give written informed consent

Exclusion criteria:

• Unstable or severe intercurrent medical conditions or active, uncontrolled infection
• History of allergic reactions to non-steroidal anti-inflammatory drugs (NSAIDs)
• History of bleeding peptic ulcer within the past 3 months

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• Recovered from all prior chemotherapy or radiotherapy
• Concurrent aspirin for cardiovascular indications allowed
• More than 2 weeks since prior and no other concurrent NSAIDs

Exclusion criteria:

• Had radiotherapy or chemotherapy within 3 weeks (nitrosoureas or mitomycin C within 6 weeks) prior to anticipated first day of dosing
• Undergoing concurrent therapy with other investigational agents or antineoplastic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Maximum tolerated dose
Survival
Time to failure

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Przemyslaw W. Twardowski, MD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: October 25, 2007
• First Submitted That Met QC Criteria: October 26, 2007
• First Posted (Estimate): October 30, 2007

Study Record Updates

• Last Update Posted (Estimate): November 22, 2012
• Last Update Submitted That Met QC Criteria: November 21, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cyclooxygenase 2 Inhibitors; Etoposide; Celecoxib
• Other Study ID Numbers: 01036; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-01036; CDR0000570381 (Registry Identifier: NCI PDQ)