A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer
Phase I Trial of Intratumoral Administration of a Measles Virus Derivative Expressing the Helicobacter Pylori Neutrophil-Activating Protein (NAP) (MV-s-NAP) in Patients With Metastatic Breast Cancer
3 other identifiers
interventional
54
1 country
1
Brief Summary
This phase I trial investigates the side effects and best dose of using a modified measles virus, MV-s-NAP, in treating patients with invasive breast cancer that has spread to other places in the body (metastatic). Both the unmodified vaccination measles virus (MV-Edm) and this modified virus (MV-s-NAP) have been shown to multiply in and destroy breast cancer cells in the test tube and in research mice. MV-s-NAP has been altered by having an extra gene (piece of deoxyribonucleic acid \[DNA\]) so that virus can make a protein called helicobacter pylori neutrophil activating protein (NAP) which is normally expressed in inflammatory reactions. Monitoring blood, urine, tissue, and throat swab samples, and using imaging tests may help to determine whether MV-s-NAP has any impact on the amount of disease present in metastatic breast cancer patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Sep 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 17, 2020
CompletedFirst Posted
Study publicly available on registry
August 21, 2020
CompletedStudy Start
First participant enrolled
September 23, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 15, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 15, 2027
January 8, 2026
January 1, 2026
6.9 years
August 17, 2020
January 6, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Maximum tolerated dose
This is defined as the highest dose level among those under consideration where at most one of 6 patients develops a dose limiting toxicity, and two or more of the 3-6 patients treated at the next higher dose level develop a dose limiting toxicity.
During the first cycle of treatment (each cycle = 21 days)
Best tumor response
The best tumor response in the injected and non-injected lesion will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results will be tabulated for the entire cohort and by breast cancer subtype in terms of whether there was response in none of the lesions, only the injected lesion, or both lesions.
Up to 2 years
Incidence of adverse events
The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity, as well as the percentage of patients developing a severe (grade 3 or higher) toxicity, will be determined.
Up to 2 years
Measles virus viremia
Defined as detection of any titer of virus by quantitative real time-polymerase chain reaction performed with patient peripheral blood mononuclear cells. Viremia will be examined in terms of the day and dose level it was detected, as well as the time to recovery.
Up to 2 years
Peripheral immune response
Peripheral immune response specific to measles virus is defined as detection of serum IgG anti-measles antibody levels of \> 20.0 EU/mL by the Enzyme Immunoassay. Peripheral anti-neutrophil activating protein (NAP) transgene response will be represented by antibody titers determined by an antigen-mediated enzyme linked immunosorbent assay against purified helicobacter pylori NAP antigen. Systemic induction of HMGB1 will also be determined. All of these factors will be examined in terms of the day and dose level they were detected, as well as the time to recovery. For each dose level, the point at which viral replication and measles virus shedding is no longer seen will be tabulated.
Up to 2 years
Secondary Outcomes (3)
Tumor response
Up to 2 years
Progression-free survival (PFS)
Up to 2 years
Overall survival (OS)
Up to 2 years
Study Arms (3)
Cohort 1 (single treatment MV-s-NAP)
EXPERIMENTALPatients receive MV-s-NAP IT on day 1 in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy, and blood and urine sample collection throughout the study.
Cohort 2 (Every 21 day MV-s-NAP)
EXPERIMENTALPatients receive MV-s-NAP IT on day 1 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy, and blood and urine sample collection throughout the study. (CLOSED TO ACCRUAL 6/9/2025)
Cohort 3 (Every 14 day MV-s-NAP)
EXPERIMENTALPatients receive MV-s-NAP IT on day 1 of each cycle. Cycles repeat every 14 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, MRI, tumor biopsy and blood and urine sample collection throughout the study.
Interventions
Undergo CT scan
Undergo tumor biopsy
Given IT
Undergo MRI
Undergo blood and urine sample collection
Eligibility Criteria
You may qualify if:
- Age \>= 18 years
- COHORT 1 ONLY: Pathologically confirmed invasive breast adenocarcinoma with documented estrogen receptor (ER)/progesterone receptor (PR) /HER2 status and radiographic evidence of distant metastatic disease
- COHORTS 2 \& 3 ONLY: Pathologically confirmed invasive breast adenocarcinoma with documented ER/PR/HER2 status and radiographic evidence of distant metastatic or recurrent disease
- COHORT 1 ONLY: Radiographic evidence of distant metastatic disease (using 7th edition American Joint Committee on Cancer \[AJCC\] criteria) with two discrete sites of measurable disease
- COHORTS 2 \& 3 ONLY: Radiographic evidence of distant metastatic or recurrent disease (using 8th edition AJCC criteria) with at least one site of measurable disease
- Prior therapies:
- Patients with ER/PR positive, HER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease and no longer be candidates for standard endocrine therapy or combination of endocrine therapy with other agents such as CDK4/6 inhibitors
- Patients with HER2 positive breast cancer irrespective of ER/PR status must have received or no longer be candidates for HER2 directed therapy with trastuzumab or pertuzumab
- Patients with ER/PR/HER2 negative breast cancer must have progressed through at least one prior cytotoxic regimen for advanced disease
- COHORT 1: At least one site of recurrent/metastatic disease that measures \> 1 cm in greatest dimension (\> 2 cm for lung lesions) and is amenable to safe percutaneous intratumoral administration of MV-s-NAP as determined by an interventional radiologist
- COHORTS 2 \& 3 ONLY: At least 1 site of recurrent/metastatic disease measuring \> 1 cm in greatest dimension \[\> 2 cm for lung lesions\] (Note that if the lesion injected in cycle 1 is not amenable to re-injection, another lesion could be selected for injection
- Absolute neutrophil count (ANC) \>= 1500/uL (=\< 7 days prior to registration)
- Platelets (PLT \>= 100,000/uL) (=\< 7 days prior to registration)
- Total bilirubin =\< institutional upper limit of normal (=\< 7 days prior to registration)
- Aspartate aminotransferase (AST) =\< 2 x upper limit of normal (ULN) (=\< 7 days prior to registration)
- +9 more criteria
You may not qualify if:
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Clinical or radiographic suspicion of impending visceral crisis due to invasion or compression by tumor
- Active infection =\< 5 days prior to registration
- History of other malignancy =\< 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix
- Any of the following prior therapies:
- Chemotherapy =\< 3 weeks prior to registration
- Immunotherapy =\< 4 weeks prior to registration
- HER2 directed therapy =\< 3 weeks prior to registration
- Targeted therapy =\< 2 weeks prior to registration (e.g., CDK4/6 inhibitors, everolimus)
- Investigational agent =\< 4 weeks prior to registration
- Any viral or gene therapy prior to registration
- Failure to fully recover from acute, reversible effects of prior systemic therapy regardless of interval since last treatment
- New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or supraventricular tachycardia \[SVT\])
- Untreated or progressive central nervous system (CNS) metastases
- NOTE: Patients with a history of treated brain metastases (surgical resection, whole brain radiation, and/or stereotactic radiosurgery) are eligible only if they are asymptomatic and have stable MRI scans for 3 consecutive months, including \< 28 days of study entry
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Publications (1)
Viker KB, Steele MB, Iankov ID, Concilio SC, Ammayappan A, Bolon B, Jenks NJ, Goetz MP, Panagioti E, Federspiel MJ, Liu MC, Peng KW, Galanis E. Preclinical safety assessment of MV-s-NAP, a novel oncolytic measles virus strain armed with an H . pylori immunostimulatory bacterial transgene. Mol Ther Methods Clin Dev. 2022 Jul 31;26:532-546. doi: 10.1016/j.omtm.2022.07.014. eCollection 2022 Sep 8.
PMID: 36092362DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Siddhartha Yadav, MD
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 17, 2020
First Posted
August 21, 2020
Study Start
September 23, 2020
Primary Completion (Estimated)
August 15, 2027
Study Completion (Estimated)
August 15, 2027
Last Updated
January 8, 2026
Record last verified: 2026-01