Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors

Study Overview
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Brief Summary
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Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have metastatic or unresectable solid tumors. 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.

Detailed Description
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OBJECTIVES: I. Determine the maximum tolerated dose, recommended phase II dose, and associated toxic effects of the triple combination of continuous infusion fluorouracil, weekly gemcitabine, and oxaliplatin in patients with metastatic or unresectable solid tumors. II. Define sequence dependent toxic effects, if any, and establish pharmacokinetic and pharmacodynamic relationships in context of this triple combination chemotherapy in this patient population. OUTLINE: This is a dose-escalation study of oxaliplatin and gemcitabine. For course 1, and then course 3 and beyond, patients receive oxaliplatin IV over 2 hours on day 1, followed by gemcitabine IV over 30 minutes on days 1 and 8, and then fluorouracil IV continuously on days 1-14. For course 2, patients receive treatment in the same manner as in course 1, except gemcitabine is given initially, followed by oxaliplatin, and then fluorouracil. Treatment continues every 21 days in the absence of unacceptable toxicity or disease progression. Cohorts of 1-6 patients receive escalating doses of oxaliplatin and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose (RPTD) is defined as the dose preceding MTD. Once RPTD is defined, the cohort is expanded to an additional 13 patients. These patients receive a fixed dose of oxaliplatin, gemcitabine, and fluorouracil as determined by the phase I dose escalation portion of this study. Patients are followed for disease progression.

Official Title
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Phase I Study of Oxaliplatin in Combination With 5-Fluorouracil and Gemcitabine in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or clinically confirmed metastatic or unresectable solid tumor for which no standard curative or palliative therapy exists or is no longer No known brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal Proven Gilbert's syndrome (UGT1A1 promoter mutation or clinical documentation of stress bilirubin levels) allowed AST/ALT no greater than 3 times upper limit of normal Renal: Creatinine normal OR Creatinine clearance at least 60 mL/min Cardiovascular: No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Pulmonary: No unexplained respiratory problems (e.g., nonproductive cough, dyspnea, rales, pulmonary infiltrates, hypoxia, or tachypnea) Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No clinical evidence of neuropathy No prior allergy to platinum compounds No prior allergy to antiemetics appropriate for administration in conjunction with protocol directed chemotherapy No other concurrent uncontrolled illness (e.g., active infection) PRIOR CONCURRENT THERAPY: Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and platinum) and recovered No more than 1 prior chemotherapy regimen for cancer Radiotherapy: At least 4 weeks since prior radiotherapy Other: No concurrent antiretroviral agents (HAART) No other concurrent investigational agents or commercial therapies

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>See detailed description. | Drug: fluorouracil<br> <br> Drug: gemcitabine hydrochloride<br> <br> Drug: oxaliplatin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific