Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

VNP20009 in Treating Patients With Advanced or Metastatic Solid Tumors That Have Not Responded to Previous Therapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over Pharmaceutical / Industry VION-CLI-005 NCI-V99-1581, NCT00004216

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.

Entry 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)

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

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

Expected Enrollment

A total of 12-40 patients will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Vion Pharmaceuticals, Incorporated

Mario Sznol, MD, Protocol chair		Ph: 203-498-4210

Registry Information
Official Title		A Phase I Trial of a Live, Genetically Modified Salmonella Typhimurium (VNP20009) for the Treatment of Cancer by Intratumoral Injection
Trial Start Date		1999-08-02
Registered in ClinicalTrials.gov		NCT00004216
Date Submitted to PDQ		1999-12-02
Information Last Verified		2007-12-28

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