Combination Chemotherapy in Treating Patients With Advanced Cancer That is Metastatic or Cannot Be Removed By Surgery

A Phase I Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in Combination With Oral Capecitabine in Patients With Advanced Malignancy

This phase I trial studies the side effects and best dose of capecitabine when given together with oxaliplatin, leucovorin calcium, and fluorouracil in treating patients with advanced cancer that is metastatic or cannot be removed by surgery. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: pharmacological study; Drug: capecitabine

Detailed Description

PRIMARY OBJECTIVES:

I. To establish the MTD and toxicity profile of oral capecitabine in combination with q 2 weekly intravenous oxaliplatin in patients with advanced malignancies.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetic parameters of capecitabine at the recommended phase II dose for combinations of capecitabine, oxaliplatin, 5-fluorouracil, and leucovorin, as well as for the combination of capecitabine and oxaliplatin.

II. To observe for and record any antitumor activity.

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

Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV on days 1 and 15. Patients also receive oral capecitabine every 8 hours on days 1-2 and 15-16. Leucovorin calcium and fluorouracil administration is held at dose level 4 and above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics

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:

• Patients must have histologically or cytologically confirmed malignancy which is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• There is no limit on prior therapies
• ECOG performance status 0-2
• Leukocytes >= 3,000/ul
• Absolute neutrophil count >= 1,500/ul
• Platelets >= 100,000/ul
• Total bilirubin =< 1.5 mg/dL
• AST (SGOT)/ALT (SGPT) =< 2.5 x institutional upper limit of normal
• Creatinine clearance >= 50 mL/min as calculated by the Cockroft-Gault formula
• Patients with no >= grade 2 (Common Toxicity Criteria [CTC] 2.0) neuropathy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Breastfeeding should be discontinued if the mother is treated with oxaliplatin
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
• Patients undergoing therapy with other investigational agents
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities
• History of allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or unstable angina pectoris, or cardiac arrhythmia
• Pregnant and nursing women are excluded from this study because oxaliplatin is a DNA alkylating agent with the potential for teratogenic or abortifacient effects
• Human immunodeficiency virus (HIV)-positive patients receiving anti-retroviral therapy (HAART) are excluded from the study

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 (combination chemotherapy); Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV, and fluorouracil IV on days 1 and 15. Patients also receive oral capecitabine every 8 hours on days 1-2 and 15-16. Leucovorin calcium and fluorouracil administration is held at dose level 4 and above. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: oxaliplatin; Given IV; Other Names: 1-OHP; Dacotin; Dacplat; Eloxatin; L-OHP; Drug: leucovorin calcium; Given IV; Other Names: CF; CFR; LV; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Drug: capecitabine; Given orally; Other Names: Xeloda; CAPE; Ro 09-1978/000

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD, defined as the highest dose level which results in DLT in fewer than 2/6 patients, graded according to the NCI CTC version 2.0	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events, graded according to NCI CTC version 2.0		Up to 6 years
Overall survival	Estimated using the product-limit method of Kaplan and Meier.	Up to 6 years
Time to progression	Estimated using the product-limit method of Kaplan and Meier.	Up to 6 years
Duration of response	Estimated using the product-limit method of Kaplan and Meier.	Up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: August 5, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Calcium-Regulating Hormones and Agents; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin; Calcium; Levoleucovorin
• Other Study ID Numbers: NCI-2013-00004 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062491 (U.S. NIH Grant/Contract); NCI-5904; WCCC-CO-02901; CO 02901 (Other Identifier: University of Wisconsin Hospital and Clinics); 5904 (Other Identifier: CTEP)