VNP20009 in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Therapy
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 or metastatic solid tumors that have not responded to previous therapy.
|Unspecified Adult Solid Tumor, Protocol Specific||Biological: salmonella VNP20009 Drug: cefixime Drug: ceftriaxone sodium Drug: ciprofloxacin Drug: trimethoprim-sulfamethoxazole||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intratumoral Injection|
|Study Start Date:||August 1999|
|Study Completion Date:||January 2008|
OBJECTIVES: I. Determine the maximum tolerated dose and safety of intratumoral live, genetically modified Salmonella typhimurium (VNP20009) in patients with refractory, superficial solid tumors. II. Determine the efficacy of VNP20009 in these patients.
OUTLINE: This is a dose-escalation study. Patients receive intratumorally injected live, genetically modified Salmonella typhimurium (VNP20009) on day 0. The tumor is biopsied on day 14. Cohorts of 3-6 patients receive escalating doses of VNP20009 until the maximum tolerated dose (MTD) or the optimal biologic dose (OBD) is determined. The MTD is defined as the highest dose in which no more than 1 patient in a cohort of 6 experiences dose-limiting toxicity (DLT). The OBD is defined as the dose at which 3-6 patients of a cohort have greater than 10 million colony-forming units of VNP20009 per gram in the tumor biopsy. Prior to reaching the OBD, 2 to 3 additional patients may be entered at a previous dose level shown to be safe to undergo biopsy of the injected lesion between days 5 and 8. Patients are assessed for systemic tumor response 4-5 weeks after treatment. If the injected lesion is stable or responding, and non-injected lesions have not grown, patients may receive up to 2 additional courses of treatment. Patients receive one of the following antibiotic regimens upon evidence of progressive disease, DLT, or discontinuation from the study: First line: Ciprofloxacin IV or orally every 12 hours on day 1 then orally twice a day for 18 days Second line: Ceftriaxone IV on day 1 then cefixime orally for 16 days Third line: Co-trimoxazole orally twice a day for 21 days Patients are followed for an additional 4 weeks after initiation of antibiotic therapy.
PROJECTED ACCRUAL: A total of 12-40 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004216
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center|
|Cleveland, Ohio, United States, 44195|
|United States, Texas|
|Mary Crowley Medical Research Center|
|Dallas, Texas, United States, 75246|
|Study Chair:||Mario Sznol, MD||Vion Pharmaceuticals|