VNP20009 in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Therapy
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific
Intervention: cefixime (Drug); ceftriaxone sodium (Drug); ciprofloxacin (Drug); salmonella VNP20009 (Drug); trimethoprim-sulfamethoxazole (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Vion Pharmaceuticals Official(s) and/or principal investigator(s):
Mario Sznol, MD, Study Chair, Affiliation: Vion Pharmaceuticals
Summary
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.
Clinical Details
Official title: A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intratumoral Injection
Study design: Treatment
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS: Histologically proven advanced or metastatic solid tumors that
have failed prior therapy and no other therapy is available At least 1 tumor mass of a size
that makes intratumoral injection feasible and biopsy or fine needle aspiration possible
Major surgery for cancer not required No lymphoma No concurrent brain metastases
(previously treated brain metastases with no evidence of recurrence allowed)
PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance
status: Karnofsky 70-100% OR ECOG 0-1 Life expectancy: At least 3 months Hematopoietic:
Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hematocrit at
least 30% (transfusion allowed) No bleeding disorder Hepatic: Bilirubin no greater than 1. 5
times upper limit of normal (ULN) ALT/AST no greater than 1. 5 times ULN (3 times ULN in the
presence of liver metastases) Alkaline phosphatase no greater than 1. 5 times ULN (3 times
ULN in the presence of liver metastases) PT and aPTT no greater than 1. 5 times ULN No end
stage liver disease Renal: Creatinine no greater than 1. 5 times ULN No urinary tract stones
No end stage renal disease Cardiovascular: No known valvular disease or ischemic peripheral
vascular disease No clinically significant atherosclerotic disease or arterial aneurysm(s)
No unstable angina No active coronary artery disease requiring medication No myocardial
infarction within the past 6 months No congenital heart failure or cardiac arrhythmia
requiring medication Pulmonary: No severe oxygen-dependent chronic obstructive pulmonary
disease Other: HIV negative Not pregnant or nursing Negative pregnancy test Fertile
patients must use effective contraception Permanent central venous catheters and other
indwelling devices allowed if easily removed or replaced No gallstones No active infection
No Salmonella infection within the past 6 months No fever caused by tumor or unknown cause
(daily temperature no greater than 38 degrees C) No immunodeficiency No other
life-threatening illness No commercial food handler, day-care worker, or health-care worker
who plans to continue employment during protocol treatment No allergy to quinolone or
cephalosporin antibiotics
PRIOR CONCURRENT THERAPY: Biologic therapy: At least 6 months since any prior bone marrow
transplantation At least 4 weeks since prior biologic therapy and recovered No other
concurrent biologic therapy No prior allogeneic transplants Chemotherapy: At least 4 weeks
since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered No
concurrent chemotherapy Endocrine therapy: At least 2 weeks since prior hormonal therapy No
concurrent steroids Radiotherapy: At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy Surgery: See Disease Characteristics At least 2 weeks since
prior surgery and recovered No artificial implant (e. g., heart valves or prosthetic hips or
knees) No prior splenectomy Other: No other concurrent antibiotics No concurrent
immunosuppressives No concurrent medications that directly or indirectly suppress the
immune system
Locations and Contacts
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States
Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio 44195, United States
Mary Crowley Medical Research Center, Dallas, Texas 75246, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: August 1999
Last updated: May 23, 2008
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