A vaccine using modified measles virus for treating 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

This study is testing a modified measles virus vaccine to see if it can safely help people with metastatic breast cancer by shrinking their tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Mayo Clinic (other)
• Drugs / interventions: trastuzumab, pertuzumab, denosumab, Chemotherapy, Immunotherapy, radiation
• Locations: 1 site (Rochester, Minnesota)
• Trial ID: NCT04521764 on ClinicalTrials.gov

What this trial studies

This phase I trial evaluates the safety and optimal dosage of a modified measles virus, MV-s-NAP, administered intratumorally to patients with metastatic breast cancer. The study aims to determine the maximum tolerated dose and assess the side effects of this innovative treatment. Additionally, it will monitor the antitumor efficacy through imaging tests and biological samples to evaluate the virus's impact on cancer cells. The trial includes two cohorts based on specific eligibility criteria related to breast cancer characteristics and prior treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with pathologically confirmed invasive breast adenocarcinoma and evidence of metastatic disease.

Not a fit: Patients with early-stage breast cancer or those who have not progressed through prior therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for patients with advanced metastatic breast cancer.

How similar studies have performed: While the use of oncolytic viruses in cancer treatment is an emerging field, this specific approach with MV-s-NAP is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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)
* 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) is permitted 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 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."

Where this trial is running

Rochester, Minnesota

• Mayo Clinic in Rochester — Rochester, Minnesota, United States (RECRUITING)

Study contacts

• Principal investigator: Siddhartha Yadav, MD — Mayo Clinic in Rochester
• Study coordinator: Clinical Trials Referral Office

Conditions: Anatomic Stage IV Breast Cancer AJCC v8, Invasive Breast Carcinoma, Metastatic Breast Adenocarcinoma, Recurrent Breast Carcinoma, Stage IV Breast Cancer AJCC v6 and v7