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


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 Intravenous Administration


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.

Inclusion Criteria


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

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:

CDR0000068187

NCT ID:

NCT00006254

Start Date:

May 2000

Completion Date:

Related Keywords:

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

Name

Location

Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195