Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04521764
Other study ID # MC1733
Secondary ID NCI-2020-0600917
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 23, 2020
Est. completion date August 15, 2027

Study information

Verified date April 2024
Source Mayo Clinic
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 33
Est. completion date August 15, 2027
Est. primary completion date August 15, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age >= 18 years - 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 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."

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Oncolytic Measles Virus Encoding Helicobacter pylori Neutrophil-activating Protein
Given IT

Locations

Country Name City State
United States Mayo Clinic in Rochester Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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)
Primary 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
Primary 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
Primary 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
Primary 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 Tumor response 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. Up to 2 years
Secondary Progression-free survival time From study entry to the documentation of disease progression, assessed up to 2 years
Secondary Overall survival time From study entry to death due to any cause, assessed up to 2 years
See also
  Status Clinical Trial Phase
Suspended NCT05673200 - Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer Phase 1
Active, not recruiting NCT03218826 - PI3Kbeta Inhibitor AZD8186 and Docetaxel in Treating Patients Advanced Solid Tumors With PTEN or PIK3CB Mutations That Are Metastatic or Cannot Be Removed by Surgery Phase 1
Recruiting NCT03723928 - S1703 Serum Tumor Marker Directed Disease Monitoring in Patients With Hormone Receptor Positive Her2 Negative Metastatic Breast Cancer N/A
Suspended NCT03737695 - Clinical Information and Biospecimen Collection From Patients With Recurrent or Stage IV Breast Cancer
Active, not recruiting NCT04316117 - Using FDG-PET/CT to Assess Response of Bone-Dominant Metastatic Breast Cancer, FEATURE Study Phase 2
Not yet recruiting NCT04529044 - 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer Phase 2
Recruiting NCT04862585 - Safely Stopping Pre-medications in Patients With Breast Cancer Who Are Receiving Paclitaxel Phase 2/Phase 3
Completed NCT00338728 - Letrozole and Imatinib Mesylate in Treating Postmenopausal Participants With Estrogen or Progesterone Positive Metastatic Breast Cancer Phase 2
Withdrawn NCT05967286 - Olaparib and Alpelisib for Treatment of Metastatic Breast Cancer, A ComboMATCH Treatment Trial Phase 2
Recruiting NCT04673448 - Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer Phase 1
Active, not recruiting NCT05081492 - CF33-hNIS-antiPDL1 for the Treatment of Metastatic Triple Negative Breast Cancer Phase 1
Recruiting NCT05318469 - Ivermectin and Balstilimab for the Treatment of Metastatic Triple Negative Breast Cancer Phase 1/Phase 2
Not yet recruiting NCT05539365 - Dendritic Cell-Based Treatment Plus Immunotherapy for the Treatment of Metastatic or Unresectable Triple Negative Breast Cancer Phase 2
Terminated NCT05198843 - Testing an Omega-3 Fatty Acid-Based Anti-Cancer Therapy for Patients With Triple-Negative Inflammatory Breast Cancer That Has Spread to Other Parts of the Body Phase 1/Phase 2
Active, not recruiting NCT04514484 - Testing the Combination of the Anti-cancer Drugs XL184 (Cabozantinib) and Nivolumab in Patients With Advanced Cancer and HIV Phase 1
Recruiting NCT05751668 - Finding an Effective Dose of GM1 to Reduce or Prevent Neuropathy (Numbness or Weakness) Due to Treatment With Paclitaxel (Phase II) Phase 2
Suspended NCT04906369 - Optimizing Treatment of Stage IV Breast Cancer Through Real-Time Disease Monitoring
Completed NCT03291938 - IACS-010759 in Advanced Cancers Phase 1
Recruiting NCT04314401 - National Cancer Institute "Cancer Moonshot Biobank"
Withdrawn NCT04351230 - T-DM1 With or Without Abemaciclib for the Treatment of HER2-Positive Metastatic Breast Cancer Phase 2