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A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intratumoral Injection


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intratumoral Injection


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Mario Sznol, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vion Pharmaceuticals

Authority:

United States: Federal Government

Study ID:

CDR0000067446

NCT ID:

NCT00004216

Start Date:

August 1999

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific

Name

Location

Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Mary Crowley Medical Research CenterDallas, Texas  75246