Study of Clostridium Novyi-NT Spores in Solid Tumors Malignancies
http://www.clinicaltrials.gov/ct/show/NCT00358397?order=3

This study is currently recruiting patients.
Verified by Sidney Kimmel Comprehensive Cancer Center July 2006
Sponsored by: Sidney Kimmel Comprehensive Cancer Center
Information provided by: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00358397

Purpose
One time IV infusion of Clostridium novyi-NT spores to treat solid
tumors which have not responded to standard therapy.
Condition Intervention Phase
Solid Tumors
Drug: Costridium novyi-NT spores
Phase I

MedlinePlus consumer health information

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled,
Single Group Assignment, Safety/Efficacy Study

Official Title: Phase I Safety Study of Clostridium Novyi-NT Spores in
Patients With Treatment-Refractory Solid Tumor Malignancies
Further study details as provided by Sidney Kimmel Comprehensive
Cancer Center:
Primary Outcomes: To determine the safety profile, dose limiting
toxicities (DLT), and maximum tolerated dose (MTD) of C. novyi–NT in
humans with treatment-refractory solid tumor malignancies when given
as a single intravenous injection.
Secondary Outcomes: To document preliminary evidence of anti-tumor
activity of C. novyi-NT in humans with treatment-refractory solid
tumor malignancies when given as a single intravenous injection.; To
analyze the pharmacokinetics of C. novyi-NT after administration to
humans with treatment-refractory solid tumor malignancies when given
as a single intravenous injection.; To measure the host immune and
inflammatory response to C. novyi-NT in humans with
treatment-refractory solid tumor malignancies when given as a single
intravenous injection.
Expected Total Enrollment: 20

Study start: July 2006; Expected completion: July 2008
Last follow-up: July 2006; Data entry closure: July 2006
This is a phase I dose escalation study using a single dose of
Clostridium novyi-NT spores in patients with treatment-refractory
solid tumor malignancies. The overall objective of this study is to
determine the safety and document any preliminary evidence of
anti-tumor activity in this patient population.

Eligibility
Ages Eligible for Study: 18 Years and above, Genders Eligible for
Study: Both
Criteria

Inclusion Criteria:

1. Documented solid tumor malignancy as proven by referral CT scan
of the chest, abdomen and pelvis.
2. Referral CT scan that demonstrates a necrotic core in primary
target measuring at least 1 cm in diameter.
3. Patients must be refractory to standard chemotherapy or for whom
no standard treatment exists. At least four weeks must have elapsed
since completion of any prior chemotherapy.
4. Patients must have measurable disease; defined as at least one
lesion whose longest diameter can be accurately measured as >2 cm.
5. ECOG performance status of 0 or 1.
6. Prior locoregional therapy, including cryotherapy,
radiofrequency ablation, or regional chemotherapy is allowed if at
least 6 weeks have elapsed.
7. Prior radiation therapy is allowed. At least 6 weeks must have
elapsed since the completion of radiation therapy and the patient must
have recovered from side effects.
8. Prior systemic radionuclide therapy is allowed. At least 4 weeks
must have elapsed since completion of the therapy.
9. Prior surgery is allowed. At least 6 weeks must have elapsed
since the completion of major surgery and the patient must be fully
recovered from this surgery and any attendant post-surgical complications.
10. Patients must be 18 years of age or older
11. Patients of childbearing potential must use adequate birth
control measures
12. Negative serum pregnancy test for females of childbearing potential.

Exclusion Criteria:

1. Weight < 135 kg
2. Chronic renal failure requiring hemodialysis or peritoneal dialysis
3. Tumor lesion that is not accessible to percutaneous drainage.
4. Any single contiguous lesion greater than > 12.5 cm.
5. The sum of the largest cross-sectional diameters from any number
of non-contiguous lesions > 2 cm cannot be > 25 cm.
6. Use of any investigational drug within 30 days prior to
screening or within 5 half-lives of the agent, whichever is longer.
7. Any documented evidence of primary brain malignancy or brain
metastases
8. Patients with any clinically significant ascites or
portosystemic hypertension, chronic jaundice or cirrhosis.
9. Patients with indwelling intrahepatic arterial pumps
10. Patients with prosthetic joints, prosthetic valves, pacemakers
or any other implanted foreign materials.
11. Patients with any clinically significant pleural effusions
12. Patients with any evidence of hemodynamic compromise from a
pericardial effusion.
13. Documented cirrhosis of the liver by clinical scenarios
encompassing radiographic, clinical and laboratory results
14. Ongoing treatment with any immunosuppressive agent(s)
15. Any evidence of serious infections or history of chronic or
recurrent infectious disease in the previous 3 months.
16. Patients with opportunistic infections
17. Documented HIV infection.
18. Active or chronic Hepatitis B or Hepatitis C.
19. Presence of a transplanted solid organ.
20. History of an autoimmune disorder
21. History of Diabetes Mellitus (type I or II)
22. History of rheumatic fever, endocarditis, or greater than mild
valvular disease.
23. Patients who depend upon COX II inhibitors or NSAIDS
24. History of ongoing and active arterial vasculopathy or evidence
of end organ damage.
25. History of an ischemic insult in the previous 12 months
26. History of venous or lymphatic stasis resulting in venous stasis
ulcers or greater than 2+ edema or lymphedema.
27. History of a splenectomy
28. Patients with a documented Penicillin or Metronidazole allergy
29. Patients with a documented allergy to radiology contrast dye.
30. Patient with active diverticulitis
31. Patient with active dental abscesses
32. Patients with inflammatory bowel disease
33. Patients with angiosarcoma
34. Patients with history of a positive PPD, past TB infection or
past atypical mycobacterium infection.

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00358397

Luis A Diaz, MD 443-287-6539 ldiaz1@...

Maryland
Johns Hopkins Medical Institutes, Baltimore, Maryland, 21231,
United States; Recruiting
Luis A Diaz, MD, Principal Investigator
Katherine Thornton, MD, Sub-Investigator
Bert Vogelstein, M.D., Sub-Investigator
Ross Donehower, M.D., Sub-Investigator
Michael Choti, M.D., Sub-Investigator
Kenneth Kinzler, Ph.D., Sub-Investigator

Study chairs or principal investigators

Luis A Diaz, MD, Principal Investigator, Johns Hopkins Medicine

More Information

Publications

Diaz LA Jr, Cheong I, Foss CA, Zhang X, Peters BA, Agrawal N,
Bettegowda C, Karim B, Liu G, Khan K, Huang X, Kohli M, Dang LH, Hwang
P, Vogelstein A, Garrett-Mayer E, Kobrin B, Pomper M, Zhou S, Kinzler
KW, Vogelstein B, Huso DL. Pharmacologic and toxicologic evaluation of
C. novyi-NT spores. Toxicol Sci. 2005 Dec;88(2):562-75. Epub 2005 Sep 14.

Folkman J. A novel anti-vascular therapy for cancer. Cancer Biol Ther.
2004 Mar;3(3):338-9. Epub 2004 Mar 29. No abstract available.

Dang LH, Bettegowda C, Agrawal N, Cheong I, Huso D, Frost P, Loganzo
F, Greenberger L, Barkoczy J, Pettit GR, Smith AB 3rd, Gurulingappa H,
Khan S, Parmigiani G, Kinzler KW, Zhou S, Vogelstein B. Targeting
vascular and avascular compartments of tumors with C. novyi-NT and
anti-microtubule agents. Cancer Biol Ther. 2004 Mar;3(3):326-37. Epub
2004 Mar 12.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed

Bettegowda C, Dang LH, Abrams R, Huso DL, Dillehay L, Cheong I,
Agrawal N, Borzillary S, McCaffery JM, Watson EL, Lin KS, Bunz F,
Baidoo K, Pomper MG, Kinzler KW, Vogelstein B, Zhou S. Overcoming the
hypoxic barrier to radiation therapy with anaerobic bacteria. Proc
Natl Acad Sci U S A. 2003 Dec 9;100(25):15083-8. Epub 2003 Dec 1.

Dang LH, Bettegowda C, Huso DL, Kinzler KW, Vogelstein B. Combination
bacteriolytic therapy for the treatment of experimental tumors. Proc
Natl Acad Sci U S A. 2001 Dec 18;98(26):15155-60. Epub 2001 Nov 27.

Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Drake CG, Hipkiss EL,
Tatsumi M, Dang LH, Diaz LA Jr, Pomper M, Abusedera M, Wahl RL,
Kinzler KW, Zhou S, Huso DL, Vogelstein B. Bacteriolytic therapy can
generate a potent immune response against experimental tumors. Proc
Natl Acad Sci U S A. 2004 Oct 19;101(42):15172-7. Epub 2004 Oct 7.

Jain RK, Forbes NS. Can engineered bacteria help control cancer? Proc
Natl Acad Sci U S A. 2001 Dec 18;98(26):14748-50. No abstract available.