A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT04521764|
Recruitment Status : Recruiting
First Posted : August 21, 2020
Last Update Posted : September 10, 2022
|Condition or disease||Intervention/treatment||Phase|
|Anatomic Stage IV Breast Cancer AJCC v8 Invasive Breast Carcinoma Metastatic Breast Adenocarcinoma Prognostic Stage IV Breast Cancer AJCC v8 Recurrent Breast Carcinoma||Biological: Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein||Phase 1|
I. To determine the maximally tolerated dose (MTD) of intratumoral administration of an Edmonston strain measles virus genetically engineered to express NAP (oncolytic measles virus encoding helicobacter pylori neutrophil-activating protein (modified virus strain neutrophil activating protein [MV-s- NAP) in patients with metastatic breast cancer.
II. To determine the safety and toxicity of one-time intratumoral administration of MV-s-NAP in patients with metastatic breast cancer.
III. To determine the safety and toxicity of serial intratumoral administration of MV-s-NAP in patients with metastatic breast cancer.
I. To assess in a preliminary fashion antitumor efficacy of this approach by following radiographic response and time to progression.
Ia. Response at and away from the site of MV-s-NAP administration will be evaluated.
I. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration.
II. To determine the time course of viral infection and viral gene expression in treated/untreated lesions.
III. To determine immune response development against MV, the therapeutic s-NAP transgene, and the tumor.
IV. To obtain preliminary assessments of PD-L1 expression in tumor cells and tumor infiltrating lymphocytes (TILs).
Patients receive MV-s-NAP intratumorally (IT) on day 1 in the absence of disease progression or unacceptable toxicity. After 1 cycle of treatment, patients who experience disease progression proceed to follow-up. Patients who achieve complete response (CR), partial response (PR), or stable disease (SD) receive MV-s-NAP IT every 21 days for up to 3 additional cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months during year 1, and then every 6 months during year 2.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 23, 2020|
|Estimated Primary Completion Date :||December 10, 2022|
|Estimated Study Completion Date :||August 10, 2023|
Experimental: Treatment (MV-s-NAP)
Patients receive MV-s-NAP intratumorally (IT) on day 1 in the absence of disease progression or unacceptable toxicity. After 1 cycle of treatment, patients who experience disease progression proceed to follow-up. Patients who achieve CR, PR, or SD receive MV-s-NAP IT every 21 days for up to 3 additional cycles in the absence of disease progression or unacceptable toxicity.
Biological: Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein
- Maximum tolerated dose [ Time Frame: During the first cycle of treatment (each cycle = 21 days) ]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.
- Best tumor response [ Time Frame: Up to 2 years ]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.
- Incidence of adverse events [ Time Frame: Up to 2 years ]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.
- Measles virus viremia [ Time Frame: Up to 2 years ]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.
- Peripheral immune response [ Time Frame: Up to 2 years ]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.
- Tumor response [ Time Frame: Up to 2 years ]The best tumor response in the injected and non-injected lesion will be determined using RECIST criteria. Results will be tabulated by dose level and whether there was a response in none of the lesions, only the injected lesion, or both lesions.
- Progression-free survival time [ Time Frame: From study entry to the documentation of disease progression, assessed up to 2 years ]
- Overall survival time [ Time Frame: From study entry to death due to any cause, assessed up to 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04521764
|United States, Minnesota|
|Mayo Clinic in Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015 email@example.com|
|Principal Investigator: Minetta C. Liu|
|Principal Investigator:||Minetta C Liu||Mayo Clinic in Rochester|