Solid Tumor MalignanciesPhase 1NCT01924689
Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores to Treat Patients With Solid Tumors That Have Not Responded to Standard Therapies
A Phase 1 study testing Clostridium novyi-NT spores in people with Solid Tumor Malignancies, run by BioMed Valley Discoveries, Inc at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor Malignancies
- What is being tested?
- Clostridium novyi-NT spores
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2013to 31 Oct 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
- Alkaline phosphatase above 2.5X the ULN
- International normalized ratio (INR) greater than 1.3
- 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).
- Clinically significant pleural effusion.
- Clinically significant pericardial effusion, circumferential pericardial effusion, or any effusion greater than 1.0 cm at any location around the heart.
- Need for ongoing treatment with an immunosuppressive agent.
- History of solid organ transplantation (with the exception of a corneal transplant > 3 months prior to screening).
- History of an ischemic insult in the previous 12 months (myocardial infarction, cerebral vascular accident, ischemic tissue from injury, transient ischemic attack.
- History of a significant medical illness deemed by the PI or local investigators as unsuitable for the trial. For example:
- Symptomatic congestive heart failure ii. Psychiatric Illness/social situation that may make study dangerous iii. Unstable angina pectoris
- Asplenia.
- Antibiotic allergies that would preclude treatment for a C. novyi-NT infection.
- Treatment with antibiotics within 2 weeks (14 days) of dosing.
- Active and clinically significant systemic or localized infection.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
UT M.D. Anderson Cancer Center
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Washington University School of Medicine
St Louis, Missouri, 63110
Albert Einstein College of Medicine
The Bronx, New York, 10461
About this study
Official title: Phase I Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores in Patients With Treatment-refractory Solid Tumor Malignancies
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
- Being tested
- Clostridium novyi-NT spores
- Keywords
- Phase 1, Metastatic Disease, Solid Tumor, Malignancy, Metastases, Clinical Trial, Hypoxia, Necrosis, Intratumoral, Locally advanced cancer, Immunotherapy, Sarcoma, Chordoma, Bacteriolytic
- Medical subject headings
- Neoplasm Metastasis, Neoplasms, Hypoxia, Necrosis, Sarcoma, Chordoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clostridium novyi-NT sporesBiological
Also called bacteria, anaerobic bacteria
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.
| Study group | Role | What they receive |
|---|---|---|
| Clostridium novyi-NT spores | Experimental | Not described Receives: Biological: Clostridium novyi-NT spores |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2013 (estimated)
- Study startOct 2013
- Primary completion31 Oct 2017
- Study completion31 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMed Valley Discoveries, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01924689
- Sponsor's protocol ID
- BVDCNV2
- Status last verified
- Aug 2019
- First submitted
- 14 Aug 2013
- Last updated
- 9 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33046513
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Safety Study of Intratumoral Injection of Clostridium Novyi-NT Spores in Patients With Treatment-refractory Solid Tumor Malignancies
- ClinicalTrials.gov ID
- NCT01924689
- Acronym / sponsor ID
- BVDCNV2
- Conditions
- Solid Tumor Malignancies
- Keywords
- Phase 1, Metastatic Disease, Solid Tumor, Malignancy, Metastases, Clinical Trial, Hypoxia, Necrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- BioMed Valley Discoveries, IncIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 31 Oct 2017 (actual)
- First posted
- 16 Aug 2013 (estimated)
- Results
- Posted 9 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clostridium novyi-NT spores | Experimental | Biological: Clostridium novyi-NT spores |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (29 listed)
- 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:
- Oxygen saturation (Sp02) of less than 95% on room air.
- Mean arterial blood pressure (BP) of less than 70 mmHg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clostridium novyi-NT sporesAlso: bacteria, anaerobic bacteriaPhase 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. | Biological | Clostridium novyi-NT spores |
Primary outcome
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.
7 secondary outcomes
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)
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)
Number of Patients With Overall RECIST 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
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
Time frame: 2 years
Number of Patients With Systemic Tumor Antigen Specific T-cell Responses
Time frame: 2 years
Number of Patients With Local Tumor-specific T-cell Responses
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33046513Janku 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Clostridium novyi-NT spores in people with Solid Tumor Malignancies, run by BioMed Valley Discoveries, Inc at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Treatment-emergent Adverse Events (TEAE) (time frame: From screening until follow-up visit (up to 12 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01924689, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2019.