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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
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.
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Albert Einstein College of Medicine
The Bronx, New York, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
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
Time frame: 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.
Time frame: From screening until follow-up visit (up to 12 months)
Percentage Change in Tumor Size From Baseline of the Target Injected Lesion, Measured by Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans
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.
Time frame: 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
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.
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UT M.D. Anderson Cancer Center
Houston, Texas, United States
Time frame: At follow up (at 1 and 2, 4, and 8 months (±2 days) after dosing)
Number of Patients With Overall RECIST Response
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.
Time frame: 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
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.
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)
Number of Patients With Cytokine Responses Analyzed
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.
Time frame: 2 years
Number of Patients With Systemic Tumor Antigen Specific T-cell Responses
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.
Time frame: 2 years
Number of Patients With Local Tumor-specific T-cell Responses
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.
Time frame: 2 years