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Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores to Treat Patients With Solid Tumors That Have Not Responded to Standard Therapies

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ClinicalTrials.gov Identifier: NCT01924689
Recruitment Status : Completed
First Posted : August 16, 2013
Results First Posted : September 9, 2019
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
BioMed Valley Discoveries, Inc

Tracking Information
First Submitted Date  ICMJE August 14, 2013
First Posted Date  ICMJE August 16, 2013
Results First Submitted Date  ICMJE January 23, 2019
Results First Posted Date  ICMJE September 9, 2019
Last Update Posted Date September 9, 2019
Study Start Date  ICMJE October 2013
Actual Primary Completion Date October 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • Number of Patients With Treatment-emergent Adverse Events (TEAE) [ Time Frame: From screening until follow-up visit (up to 12 months) ]
    To determine the safety profile of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection. CTCAE: Common Terminology Criteria for Adverse Events
  • Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs) [ Time Frame: From screening until follow-up visit (up to 12 months) ]
    To determine the DLTs of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection.
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2013)
Safety and tolerability of C. novyi-NT spore administration in patients with advanced solid tumor malignancies will be measured over a 7-day inpatient admission with routine labs and continuous adverse event assessments. [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2019)
  • Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans [ Time Frame: At screening, at follow up (at 1, 2, 4, and 8 months (±2 days) after dosing) ]
    To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1. Change from baseline is presented.
  • Number of Patients With RECIST Assessment on the Injected Lesion [ Time Frame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing) ]
    To document preliminary anti-tumor activity of the injected lesion after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included a response for the injected lesion. Response and progression was evaluated using the international criteria proposed by the RECIST 1.1. Objective responses were measured by serial CT or MRI scans of the injected lesion and sites of metastatic involvement. Overall response, based on CT/MRI scan results, was based on observation of measurable and non-measurable disease as compared to baseline and nadir in target and non-target tumors per RECIST 1.1.
  • Number of Patients With Overall RECIST Response [ Time Frame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing) ]
    To document preliminary anti-tumor activity of an overall response after administering a single IT injection of C. novyi-NT in humans with treatment-refractory solid tumor malignancies. The evaluation of anti-tumor activity included an overall response.
  • Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT [ Time Frame: At Screening, at Days -1 to 0, at Days 1, 2, 3, 4, 5, 7, at follow up (at 2 months (±2 days) after dosing) ]
    To study the presence of circulating C. novyi-NT spores after administration as a single IT injection to humans with treatment-refractory solid tumor malignancies.
  • Number of Patients With Cytokine Responses Analyzed [ Time Frame: 2 years ]
    The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. The following table presents the data for the patients who had analyzable cytokine data. This table was included to simply indicate the number of patients who participated in the cytokine response analysis.
  • Number of Patients With Systemic Tumor Antigen Specific T-cell Responses [ Time Frame: 2 years ]
    The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Release of T-cell cytokines and effector molecules (interferon [IFN]-γ , Granzyme B, and tumor necrosis factor [TNF]-α) from the patient's own peripheral blood mononuclear cells (PBMCs) treated with allogenic tumor cell line lysates were quantified by Enzyme-Linked Immunosorbent Spot (ELISPOT) assays. A positive response was defined as a frequency that is significantly (p <0.05, two-tailed t-test) greater than the mean of control no-antigen wells and detectable (i.e., >1:100,000). No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol.
  • Number of Patients With Local Tumor-specific T-cell Responses [ Time Frame: 2 years ]
    The host immune and inflammatory response to C. novyi-NT spores was measured in routine blood sampling over the course of the study. Immunostaining for tumor infiltrating cells was analyzed independently by 2 investigators. Respective counting of 3 slides per patient between 5 to 20 fields of vision at 200x were scored using the modified ALLRED scoring method. Respective counts were averaged in each case. Pre and post treatment needle biopsies from injected and non-injected tumors were stained for the presence of tumor infiltrating immune cells. No patients were analyzed for Cohort 1 and Cohort 2 based on the original study protocol.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2013)
  • Anti-tumor activity of C. novyi-NT spores will be assessed with serial imaging studies such as CT scans and blood-based tumor markers. [ Time Frame: 2 years ]
  • Pharmacokinetics of the C. novyi-NT spores will be measured in routine blood sampling over the course of the study. [ Time Frame: 2 years ]
  • The host immune and inflammatory response to C. novyi-NT spores will be measured in routine blood sampling over the course of the study. [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores to Treat Patients With Solid Tumors That Have Not Responded to Standard Therapies
Official Title  ICMJE Phase I Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores in Patients With Treatment-refractory Solid Tumor Malignancies
Brief Summary This protocol will examine the safety of intratumoral administration of Clostridium Novyi-NT spores in patients with treatment-refractory solid tumor malignancies. This investigational study will measure anti-tumor activity of C. novyi-NT administered intratumoral in patients with treatment-refractory solid tumor malignancies.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor Malignancies
Intervention  ICMJE Biological: Clostridium novyi-NT spores
Phase 1 study: It will be an escalating dose design, with no intracohort escalation. The first cohort dose will begin at 1 x 10(4) spores/kg and will escalate by tripling through 5 cohorts up to 100 x 10(4) spores/kg.
Other Names:
  • bacteria
  • anaerobic bacteria
Study Arms  ICMJE Experimental: Clostridium novyi-NT spores
Intervention: Biological: Clostridium novyi-NT spores
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 8, 2017)
24
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2013)
18
Actual Study Completion Date  ICMJE October 31, 2017
Actual Primary Completion Date October 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of an advanced solid tumor malignancy. There must be a target tumor which is measureable, palpable or clearly identifiable under ultrasound or radiographic guidance and amenable to percutaneous injection of C. novyi-NT spores. The targeted lesion must have a longest diameter ≥ 1 cm and ≤ 12 cm and be measurable as defined by RECIST 1.1 criteria. The target lesion must not be located in either the thoracic, abdominal or pelvic cavities or in the brain. There must be no clinical, no functional, and no radiographic evidence of bone involvement at the site of the target lesion.
  2. History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment.
  3. At least 4 weeks have elapsed since the completion of major surgery, and the patient has fully recovered from this surgery and any post-surgical complications.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
  5. Patient is at least 18 years of age.
  6. Patient is capable of giving informed consent.
  7. Patient of childbearing potential (defined by the clinical sites' standards) is using adequate birth control measures (e.g., barrier method with spermicide; intrauterine device; implantable or injectable hormonal contraceptives; surgical sterilization) for the duration of the study and will continue to use such precautions for 12 months after receiving treatment.
  8. Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed).
  9. Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after doing.
  10. The patient has a caregiver for 28 days after dosing.

Exclusion Criteria:

  1. Positive pregnancy test.
  2. Serum creatinine level > 1.5 x the upper limit of normal (ULN), chronic renal failure requiring hemodialysis or peritoneal dialysis.
  3. Patient has any of the following hematologic parameters:

    • Platelet count equal to or less than 100,000/mm3
    • Hemoglobin less than 9.0 g/dL
    • Absolute neutrophil count (ANC) less than 1,000 /mm3
  4. Oxygen saturation (Sp02) of less than 95% on room air.
  5. Mean arterial blood pressure (BP) of less than 70 mmHg.
  6. Glasgow Coma Score (GCS) of less than 15.
  7. Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug, whichever is shorter.
  8. Documented primary brain malignancy or brain metastases.
  9. Clinically significant ascites or clinical evidence or history of portosystemic hypertension or cirrhosis.
  10. Laboratory evidence of hepatic dysfunction indicated by any of the following:

    • Bilirubin ≥ 1.5 x the ULN
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above 2.5X the ULN
    • Alkaline phosphatase above 2.5X the ULN
    • International normalized ratio (INR) greater than 1.3
  11. Patient has a foreign body which in the opinion of the treating investigator could be difficult to manage in case of infection (e.g. prosthetic hip).
  12. Clinically significant pleural effusion.
  13. Clinically significant pericardial effusion, circumferential pericardial effusion, or any effusion greater than 1.0 cm at any location around the heart.
  14. Need for ongoing treatment with an immunosuppressive agent.
  15. History of solid organ transplantation (with the exception of a corneal transplant > 3 months prior to screening).
  16. History of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack.
  17. History of a significant medical illness deemed by the PI or local investigators as unsuitable for the trial. For example:

    i. Symptomatic congestive heart failure ii. Psychiatric Illness/social situation that may make study dangerous iii. Unstable angina pectoris

  18. Asplenia.
  19. Antibiotic allergies that would preclude treatment for a C. novyi-NT infection.
  20. Treatment with antibiotics within 2 weeks (14 days) of dosing.
  21. Active and clinically significant systemic or localized infection.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01924689
Other Study ID Numbers  ICMJE BVDCNV2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party BioMed Valley Discoveries, Inc
Study Sponsor  ICMJE BioMed Valley Discoveries, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account BioMed Valley Discoveries, Inc
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP