Clinical trial NCT01924689: 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: Phase I Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores in Patients With Treatment-refractory Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor Malignancies
Keywords: Phase 1
Metastatic Disease
Solid Tumor
Malignancy
Metastases
Clinical Trial
Hypoxia
Necrosis
Intratumoral
Locally advanced cancer
Immunotherapy
Sarcoma
Chordoma
Bacteriolytic
Lead sponsor: BioMed Valley Discoveries, Inc
Sponsor class: INDUSTRY
First posted: 2013-08-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Treatment-emergent Adverse Events (TEAE)
timeFrame: From screening until follow-up visit (up to 12 months)
measure: Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs)
timeFrame: From screening until follow-up visit (up to 12 months)
Secondary outcomes:
measure: Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans
timeFrame: At screening, at follow up (at 1, 2, 4, and 8 months (±2 days) after dosing)
measure: Number of Patients With RECIST Assessment on the Injected Lesion
timeFrame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)
measure: Number of Patients With Overall RECIST Response
timeFrame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)
measure: Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT
timeFrame: 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)
measure: Number of Patients With Cytokine Responses Analyzed
timeFrame: 2 years
measure: Number of Patients With Systemic Tumor Antigen Specific T-cell Responses
timeFrame: 2 years
measure: Number of Patients With Local Tumor-specific T-cell Responses
timeFrame: 2 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: UT M.D. Anderson Cancer Center
state: Texas
Study officials:
References:
citation: Janku F, Zhang HH, Pezeshki A, Goel S, Murthy R, Wang-Gillam A, Shepard DR, Helgason T, Masters T, Hong DS, Piha-Paul SA, Karp DD, Klang M, Huang SY, Sakamuri D, Raina A, Torrisi J, Solomon SB, Weissfeld A, Trevino E, DeCrescenzo G, Collins A, Miller M, Salstrom JL, Korn RL, Zhang L, Saha S, Leontovich AA, Tung D, Kreider B, Varterasian M, Khazaie K, Gounder MM. Intratumoral Injection of Clostridium novyi-NT Spores in Patients with Treatment-refractory Advanced Solid Tumors. Clin Cancer Res. 2021 Jan 1;27(1):96-106. doi: 10.1158/1078-0432.CCR-20-2065. Epub 2020 Oct 12.