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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00043121
First received: August 5, 2002
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: oxaliplatin
Drug: leucovorin calcium
Drug: fluorouracil
Drug: capecitabine
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Oxaliplatin, 5-Fluorouracil, and Leucovorin in Combination With Oral Capecitabine in Patients With Advanced Malignancy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of adverse events, graded according to NCI CTC version 2.0 [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Time to progression [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.

  • Duration of response [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Estimated using the product-limit method of Kaplan and Meier.


Enrollment: 50
Study Start Date: June 2002
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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-fluorouracil
  • 5-Fluracil
  • 5-FU
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00043121

Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: George Wilding University of Wisconsin Hospital and Clinics
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00043121     History of Changes
Other Study ID Numbers: NCI-2013-00004, NCI-2013-00004, NCI-5904, WCCC-CO-02901, CO 02901, 5904, U01CA062491
Study First Received: August 5, 2002
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Fluorouracil
Capecitabine
Oxaliplatin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes
Protective Agents

ClinicalTrials.gov processed this record on July 22, 2014