Viral Therapy In Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Cancer or Metastatic Breast Cancer

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

Phase I Trial of Intratumoral Administration of a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01846091
• Other study ID #: MC0979
• Secondary ID: NCI-2013-00811MC
• Status: Completed
• Phase: Phase 1
• Start date: April 9, 2013
• Est. completion date: November 26, 2019

Study information

• Verified date: February 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial studies the side effects and the best dose of viral therapy in treating patients with squamous cell carcinoma of the head and neck that has returned (come back) after a period of improvement or has spread to other parts of the body or breast cancer that has spread to other parts of the body. A virus called encoding thyroidal sodium iodide symporter, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.

Description:

PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of intratumoral administration of an Edmonston strain measles virus genetically engineered to express human thyroidal sodium-iodide symporter (NIS) (oncolytic measles virus encoding thyroidal sodium iodide symporter [MV-NIS]) in patients with recurrent/metastatic squamous cell head and neck cancer. II. To determine the safety and toxicity of intratumoral administration of MV-NIS in patients with recurrent/metastatic squamous cell head and neck cancer and 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. TERTIARY OBJECTIVES: I. To determine the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging. II. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration. III. To determine humoral and cellular immune response to the injected virus. OUTLINE: This is a dose-escalation study. Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter intratumorally (IT) on day 1. After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year, and then every 6 months for 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 26, 2019
• Est. primary completion date: September 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed squamous cell carcinoma of the head and neck OR 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

• Measurable disease

• Head and neck cancer OR metastatic breast for which standard therapy is not 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; 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; ER/PR and HER2 status are defined by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines

• Patient may have more than one site of recurrence/metastatic disease but only one lesion will be injected that is >= 1 cm in size (if in the lung, the lesion must be >= 2 cm and adjacent to the pleura in the lung)

• Absolute neutrophil count (ANC) >= 1500

• Platelet (PLT) >= 100,000

• Hemoglobin (HgB) > 9.0 g/dL

• Total bilirubin =< institutional upper limit of normal (ULN)

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN

• Creatinine =< 1.0 mg/dL

• 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

• Provide informed written consent

• Willingness to return to Mayo Clinic enrolling institution for follow-up

• Willingness to provide biologic samples for correlative research purposes

• Life expectancy >= 12 weeks

Exclusion Criteria:

• Any of the following * Pregnant women * Nursing women * Men or women of childbearing potential who are unwilling to employ adequate contraception during treatment and 8 weeks following the completion of treatment

• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

• Receiving therapeutic anticoagulation (Coumadin or low molecular weight heparin)

• Active infection =< 5 days prior to registration

• History of tuberculosis or history of tuberculin purified protein derivative (PPD) positivity

• Any of the following prior therapies: * Chemotherapy =< 3 weeks prior to registration
• Immunotherapy =< 4 weeks prior to registration * Biologic therapy =< 4 weeks prior to registration * Radiation therapy =< 3 weeks prior to registration

• Failure to fully recover from acute, reversible effects defined as =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 of prior chemotherapy regardless of interval since last treatment

• Requiring blood product support

• Central nervous system (CNS) metastases or seizure disorder

• 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)

• Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids

• Current exposure to household contacts =< 15 months old or household contact with known immunodeficiency

• Willing to avoid household contacts =< 15 months old or household contact with known immunodeficiency 1 week after treatment

• Allergy to measles vaccine or history of severe reaction to prior measles vaccination

• Allergy to iodine; Note: this does not include reactions to intravenous contrast materials

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma
• Carcinoma, Squamous Cell
• Estrogen Receptor Negative
• Estrogen Receptor Positive
• Head and Neck Squamous Cell Carcinoma
• HER2/Neu Negative
• HER2/Neu Positive
• Invasive Breast Carcinoma
• Progesterone Receptor Negative
• Progesterone Receptor Positive
• Recurrence
• Recurrent Head and Neck Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Stage IV Breast Cancer
• Triple-Negative Breast Carcinoma

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Given IT

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biodistribution of virally infected cells, assessed using SPECT/CT	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to day 28
Other	Cellular immune response	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to day 28
Other	Humoral immune response	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to day 28
Other	Measles virus shedding/persistence	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to 3 months
Other	Time course of viral gene expression	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to 3 months
Other	Time course of virus elimination	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to 3 months
Other	Viral replication	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to 3 months
Other	Viremia	Descriptive statistics and simple scatter plots will form the basis of presentation. Correlations with other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). Prerequisite normality testing carried out via standard Shapiro-Wilk testing. Where patterns of correlation are indicated, ordinary and partial correlation coefficients (controlling for dose levels) will be calculated. Inferential testing for significant shifts in the correlative laboratory data carried out as a hypothesis-generating exercise.	Up to day 28
Primary	MTD defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) as assessed by the National Cancer (NCI) CTCAE v. 4.0		4 weeks
Primary	Number of toxicity incidents defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment	Assessed by the NCI CTCAE v. 4.0. Toxicity data will be summarized for MV-NIS virus cohorts.	Up to 3 months
Secondary	Number of responses using Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1	Responses will be summarized separately for MV-NIS virus by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.	Up to 2 years
Secondary	Time to tumor progression	The time to tumor progression will be summarized by Kaplan-Meier curve.	Up to 2 years