VNP20009 in Treating Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Biological therapies such as VNP20009 use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of VNP20009 in treating patients who have advanced solid tumors.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose or minimum effective dose and associated toxic effects of VNP20009 in patients with advanced solid tumors. Determine whether VNP20009 can be detected in tumors after treatment in these patients. Determine the pharmacokinetics of this treatment regimen in these patients. Determine the antitumor effects of this treatment regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive VNP20009 IV over 4 hours on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable disease or partial or complete response (CR) may receive additional courses every 35 days for up to 12 total doses or 2 courses past a CR. Cohorts of 3-6 patients receive escalating doses of VNP20009 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. An additional 6-9 patients are treated at the MTD. PROJECTED ACCRUAL: A total of 14-45 patients will be accrued for this study.

Official Title
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A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intravenous Administration

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: salmonella VNP20009


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced and/or metastatic solid tumors refractory to standard curative or palliative therapy and for which no other conventional therapy exists Measurable or evaluable metastatic disease No brain metastases unless previously treated and no evidence of recurrence No lymphoma or other hematologic malignancy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 3 months Hematopoietic: Granulocyte count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hematocrit at least 30% (transfusion allowed) No known bleeding disorder Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) ALT and AST no greater than 1.5 times ULN (3 times ULN if liver metastases present) Alkaline phosphatase no greater than 1.5 times ULN (3 times ULN if liver metastases present) PT and PTT no greater than 1.5 times ULN Hepatitis B surface antigen negative No chronic active hepatitis B No end-stage liver disease Renal: Creatinine no greater than 2.0 mg/dL No urinary tract stones No end-stage renal disease Cardiovascular: No known valvular disease No known clinically significant atherosclerotic disease, peripheral vascular disease, or arterial aneurysm No unstable angina No artificial heart valves Pulmonary: No severe oxygen-dependent chronic obstructive pulmonary disease Other: No artificial implant that cannot be removed (e.g., prosthetic hips or knees or other devices) No permanent central venous catheters No gallstones No active infection No documented Salmonella infection No tumor fever or fever of unknown origin or cause Daily maximum temperature no greater than 38.0 degrees Celsius HIV negative No documented immunodeficiency No other life-threatening illness No history of allergic reaction or hypersensitivity to quinolone or cephalosporin antibiotics No commercial food handlers, day-care workers, or health-care workers No patients unable to avoid close personal contact with severely immunosuppressed individuals (e.g., other patients on myelosuppressive cancer chemotherapy) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy and recovered Chemotherapy: At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered Endocrine therapy: At least 2 weeks since prior hormonal therapy and recovered No concurrent steroids that could depress the immune system unless indicated for severe reactions Radiotherapy: At least 4 weeks since prior radiotherapy and recovered Surgery: At least 2 weeks since prior surgery and recovered No prior splenectomy No concurrent palliative surgery Other: Recovered from any other prior anticancer therapies No concurrent antibiotics No concurrent immunosuppressives or any other medications that could suppress the immune system No other concurrent treatment for malignancy No requirement for immediate palliative treatment

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: salmonella VNP20009|nan|

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