Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: 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. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy in treating patients who have advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the pharmacokinetic profile of gemcitabine, doxorubicin HCl liposome, and vinorelbine in patients with advanced solid tumors. Determine the maximum tolerated dose of this regimen in these patients. Determine the toxicity profile of this regimen in these patients. OUTLINE: This is a dose escalation study. Patients receive doxorubicin HCl liposome IV over 1-2.5 hours on day 1, gemcitabine IV over 30 minutes on days 1 and 8, and vinorelbine IV over 6-10 minutes on days 1 and 15. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, gemcitabine, and vinorelbine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for up to 1 year. PROJECTED ACCRUAL: Approximately 9-24 patients will be accrued for this study within 12-18 months.

Official Title
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Phase I Trial of Combination Pegylated Liposomal Doxorubicin (Doxil), Vinorelbine, and Gemcitabine

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: pegylated liposomal doxorubicin hydrochloride
* Drug: vinorelbine ditartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed solid tumor not amenable to curative surgery, radiotherapy, or chemotherapy No brain metastases or primary brain tumors PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: WBC at least 3,500/mm3 Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: Bilirubin no greater than 1.2 mg/dL AST and/or ALT less than 2.5 times upper limit of normal (ULN) PT no greater than ULN (anticoagulant independent) Renal: Creatinine no greater than 1.5 mg/dL AND/OR Creatinine clearance greater than 60 mL/min Cardiovascular: No New York Heart Association class III or IV heart disease LVEF at least 45% by MUGA or echocardiogram Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem cell transplantation following high dose chemotherapy At least 3 weeks since prior biologic therapy for cancer and recovered No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy: See Disease Characteristics See Biologic therapy No more than 1 prior chemotherapy regimen No prior vinca alkaloids Prior anthracycline allowed if total dose no greater than 300 mg/m2 At least 3 weeks since prior chemotherapy (6 weeks for mitomycin or carmustine) and recovered Endocrine therapy: At least 3 weeks since prior endocrine therapy for cancer and recovered Radiotherapy: See Disease Characteristics No more than 1 prior radiotherapy regimen At least 4 weeks since prior large field radiotherapy At least 3 weeks since prior radiotherapy for cancer and recovered Surgery: Not specified

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

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|Patients receive gemcitabine IV over 30 minutes on days 1 and 8. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.|
|Drug: pegylated liposomal doxorubicin hydrochloride|Patients receive doxorubicin HCl liposome IV over 1-2.5 hours on day 1. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.|
|Drug: vinorelbine ditartrate|Patients receive vinorelbine IV over 6-10 minutes on days 1 and 15. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.|

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