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

NCT01924689 | Completed Phase 1 Results DMC

• 1 other identifier: BVDCNV2
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Treatment-emergent Adverse Events (TEAE)

  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

  From screening until follow-up visit (up to 12 months)

• Number of Patients With Adverse Events Qualified as Dose Limiting Toxicities (DLTs)

  To determine the DLTs of C. novyi-NT in humans with treatment-refractory solid tumor malignancies when administered as a single IT injection.

  From screening until follow-up visit (up to 12 months)

Secondary Outcomes (7)

• Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans

  At screening, at follow up (at 1, 2, 4, and 8 months (±2 days) after dosing)

• Number of Patients With RECIST Assessment on the Injected Lesion

  At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)

• Number of Patients With Overall RECIST Response

  At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)

• Positive Blood Cultures-Number of Patients With Presence of C. Novyi-NT

  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)

• Number of Patients With Cytokine Responses Analyzed

  2 years

Study Arms (1)

Clostridium novyi-NT spores

EXPERIMENTAL

Biological: Clostridium novyi-NT spores

Interventions

Clostridium novyi-NT spores BIOLOGICAL

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.

Also known as: bacteria, anaerobic bacteria

Clostridium novyi-NT spores

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
• Patient is at least 18 years of age.
• Patient is capable of giving informed consent.
• 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.
• Patient has no significant valvular heart disease (trace or mild valvular stenosis or regurgitation is allowed).
• Patient is able to stay within 45 minutes driving time of an emergency room for 28 days after doing.
• The patient has a caregiver for 28 days after dosing.

You may not qualify if:

• Positive pregnancy test.
• Serum creatinine level \> 1.5 x the upper limit of normal (ULN), chronic renal failure requiring hemodialysis or peritoneal dialysis.
• 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
• Oxygen saturation (Sp02) of less than 95% on room air.
• Mean arterial blood pressure (BP) of less than 70 mmHg.
• Glasgow Coma Score (GCS) of less than 15.
• Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug, whichever is shorter.
• Documented primary brain malignancy or brain metastases.
• Clinically significant ascites or clinical evidence or history of portosystemic hypertension or cirrhosis.
• 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

Sponsors & Collaborators

• BioMed Valley Discoveries, Inc: lead

Study Sites (5)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

UT M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 33046513 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms; Hypoxia; Necrosis; Sarcoma; Chordoma

Interventions

Bacterial Load

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

Bacteriological Techniques; Microbiological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Colony Count, Microbial; Investigative Techniques; Bacterial Physiological Phenomena; Microbiological Phenomena

Results Point of Contact

• Title: Brent Kreider
• Organization: BioMed Valley Discoveries, Inc.

bkreider@biomed-valley.com

816-960-4644

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: August 14, 2013
• First Posted: August 16, 2013
• Study Start: October 1, 2013
• Primary Completion: October 31, 2017
• Study Completion: October 31, 2017
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-08

Locations

US (5)