Description:
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.
Title
- Brief Title: A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer
- 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
Clinical Trial IDs
- ORG STUDY ID:
MC1733
- SECONDARY ID:
NCI-2020-06009
- SECONDARY ID:
MC1733
- SECONDARY ID:
P30CA015083
- NCT ID:
NCT04521764
Conditions
- Anatomic Stage IV Breast Cancer AJCC v8
- Invasive Breast Carcinoma
- Metastatic Breast Adenocarcinoma
- Prognostic Stage IV Breast Cancer AJCC v8
- Recurrent Breast Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein | MV Encoding NAP, MV-s-NAP, Oncolytic Measles Virus Encoding H. pylori NAP | Treatment (MV-s-NAP) |
Purpose
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.
Detailed Description
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
CORRELATIVE OBJECTIVES:
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).
OUTLINE:
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (MV-s-NAP) | Experimental | 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. | - Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein
|
Eligibility Criteria
Inclusion Criteria:
- Pathologically confirmed invasive breast adenocarcinoma with documented estrogen
receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2
(HER2) status and radiographic evidence of distant metastatic disease.
- Radiographic evidence of distant metastatic disease (using 7th edition American Joint
Committee on Cancer [AJCC] criteria) with two discrete sites of measurable disease
- No available standard therapy that is considered curative.
- NOTE: 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 (including combination
therapy that includes palbociclib or everolimus). Patients with HER2 positive
breast cancer irrespective of ER/PR status must have received or no longer be
candidates for standard HER2 directed therapy (i.e., trastuzumab, pertuzumab,
trastuzumab, emtansine, and lapatinib). Patients with ER/PR/HER2 negative breast
cancer must have progressed through at least one prior cytotoxic regimen for
advanced disease
- 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.
- NOTE: In Phase I of the trial (single injection), only one lesion will be
injected. In Phase II of the trial (3, every 3 weeks [Q3weekly] injections), the
same lesion will be injected unless the interventional radiologist determines
that lesion is not amenable to reinjection, in which case another lesion (if
present and measuring > 1 cm in greatest dimension [> 2 cm for lung lesions])
will be injected
- 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)
- Creatinine =< 1.5 x ULN (=< 7 days prior to registration)
- Hemoglobin >= 9.0 g/dL (=< 7 days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration (for women of
childbearing potential only)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Ability to provide informed written consent
- Willingness to return to the Mayo Clinic enrolling institution for follow-up
- Willingness to provide biologic samples for correlative research purposes
- Life expectancy >= 12 weeks
- Concomitant administration of a bone modifying agent (e.g., zoledronic acid or
denosumab) for the prevention or management of skeletal related events in patients
with bone metastases and documentation of tolerability with prior exposures
Exclusion Criteria:
- 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 tuberculosis or history of tuberculin skin test positivity
- 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
- Standing requirement for blood product support
- Human immunodeficiency virus (HIV) positive test result or history of other
immunodeficiency
- History of organ transplantation
- History of chronic hepatitis B or C
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)
- Any concurrent medications that the principal investigator determines could interfere
with the trial
- Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled
steroids
- Exposure to household contacts =< 15 months old or household contact with known
immunodeficiency
- Allergy to measles vaccine or history of severe reaction to prior measles vaccination
- History of receiving the measles vaccination with the "killed vaccine" between
1963-1967 without subsequent re-immunization (2 doses) with the active, live
vaccination."
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose |
Time Frame: | During the first cycle of treatment (each cycle = 21 days) |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Tumor response |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Progression-free survival time |
Time Frame: | From study entry to the documentation of disease progression, assessed up to 2 years |
Safety Issue: | |
Description: | |
Measure: | Overall survival time |
Time Frame: | From study entry to death due to any cause, assessed up to 2 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Mayo Clinic |
Last Updated
July 29, 2021