One Time Injection of Bacteria to Treat Solid Tumors That Have Not Responded to Standard Therapy

NCT00358397 | Terminated Phase 1 DMC

• 1 other identifier: J0590
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study will include a one time intravenous (IV) infusion of Clostridium novyi-NT (C. novyi-NT) spores to treat solid tumors which have not responded to standard therapy.

Conditions

Tumors

Keywords

Solid Tumor; Clostridial; Spore-forming bacteria; hypoxia; anaerobes; Clostridium novyi; Bacteria; Bacteriolytic; Tumor lysis; Necrosis; Colon Cancer; Lung Cancer; Sarcoma; Bladder Cancer; Rectal Cancer; Gastric Cancer; Pancreatic Cancer; Experimental Therapy; Solid Tumors

Outcome Measures

Primary Outcomes (1)

• 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

  2 years

Secondary Outcomes (3)

• 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

  2 years

• 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

  2 years

• 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

  2 years

Study Arms (1)

Treatment arm

EXPERIMENTAL

Drug: Clostridium novyi-NT spores

Interventions

Clostridium novyi-NT spores DRUG

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven solid tumor malignancy as proven by referral CT scan of the chest, abdomen and pelvis.
• 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.
• Patients must have measurable disease; defined as at least one lesion whose longest diameter can be accurately measured as \>2 cm.
• ECOG performance status of 0 or 1.
• Prior locoregional therapy, including cryotherapy, radiofrequency ablation, or regional chemotherapy is allowed if at least 6 weeks have elapsed.
• 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.
• Prior systemic radionuclide therapy is allowed. At least 4 weeks must have elapsed since completion of the therapy.
• 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 postsurgical complications.
• Patients must be 18 years of age or older
• Patients of childbearing potential must use adequate birth control measures (e.g., abstinence, barrier method with spermicide; or use by partner of oral contraceptives, intrauterine device, implantable or injectable contraceptives \[i.e., Norplant or Depo-Provera\] or surgical sterilization) for the duration of the study and should continue such precautions for 12 months after receiving treatment.
• Screening physical exam must be obtained less than 7 days prior to treatment and the results must meet the following criteria:
• Temperature range: \< 38.0 and greater and \>36.0
• Respiratory rate: 10-20 breaths per minute
• Heart rate: 50 - 85 beats per minute
• Blood pressure: Systolic blood pressure greater than 90 mm Hg and less than 155 mm Hg

You may not qualify if:

• Weight \> 135 kg
• Chronic renal failure requiring hemodialysis or peritoneal dialysis
• Patients with renal cysts.
• Tumor lesion that is not accessible to percutaneous drainage.
• Any single contiguous lesion greater than \> 12.5 cm (largest diameter).
• The sum of the largest cross-sectional diameters from any number of non-contiguous lesions \> 2 cm cannot be \> 25 cm.
• Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
• Any documented evidence of primary brain malignancy or brain metastases
• Patients with any clinically significant ascites or portosystemic hypertension, chronic jaundice or cirrhosis.
• Patients with indwelling intrahepatic arterial pumps
• Patients with prosthetic joints, prosthetic valves, pacemakers or any other implanted foreign materials. (non-CNS surgical clips or staples are excluded)
• Patients with any clinically significant pleural effusions
• Patients with any evidence of hemodynamic compromise from a pericardial effusion, circumferential pericardial effusion, or any effusion greater than 1.0 cm at any location around the heart.
• Documented cirrhosis of the liver by clinical scenarios encompassing radiographic,clinical and laboratory results
• Ongoing treatment with any immunosuppressive agent(s)

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Medical Institutes

Baltimore, Maryland, 21231, United States

Location

Related Publications (7)

• 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. doi: 10.1093/toxsci/kfi316. Epub 2005 Sep 14.

  PMID: 16162850 BACKGROUND

• Folkman J. A novel anti-vascular therapy for cancer. Cancer Biol Ther. 2004 Mar;3(3):338-9. doi: 10.4161/cbt.3.3.708. Epub 2004 Mar 29. No abstract available.

  PMID: 14726666 BACKGROUND

• 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. doi: 10.4161/cbt.3.3.704. Epub 2004 Mar 12.

  PMID: 14739784 BACKGROUND

• 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. doi: 10.1073/pnas.2036598100. Epub 2003 Dec 1.

  PMID: 14657371 BACKGROUND

• 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. doi: 10.1073/pnas.251543698. Epub 2001 Nov 27.

  PMID: 11724950 BACKGROUND

• 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. doi: 10.1073/pnas.0406242101. Epub 2004 Oct 7.

  PMID: 15471990 BACKGROUND

• Jain RK, Forbes NS. Can engineered bacteria help control cancer? Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14748-50. doi: 10.1073/pnas.261606598. No abstract available.

  PMID: 11752416 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Hypoxia; Necrosis; Colonic Neoplasms; Lung Neoplasms; Sarcoma; Urinary Bladder Neoplasms; Rectal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Rectal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Luis A Diaz, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2006
• First Posted: July 31, 2006
• Study Start: July 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: October 14, 2016

Record last verified: 2016-10

Locations

US (1)