Fallopian Tube Clear Cell Adenocarcinoma, Fallopian Tube Endometrioid Adenocarcinoma, Fallopian Tube Mucinous Adenocarcinoma, Fallopian Tube Serous Adenocarcinoma, Fallopian Tube Transitional Cell Carcinoma, Fallopian Tube Undifferentiated Carcinoma, Malignant Ovarian Brenner Tumor, Ovarian Clear Cell Adenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Ovarian Serous Adenocarcinoma, Ovarian Transitional Cell Carcinoma, Ovarian Undifferentiated Carcinoma, Primary Peritoneal Serous Adenocarcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Conditions
Brief summary
This phase I/II trial studies the side effects and best dose of oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) infected mesenchymal stem cells and to see how well it works in treating patients with ovarian, primary peritoneal or fallopian tube cancer that has come back. Mesenchymal stem cells may be able to carry tumor-killing substances directly to ovarian, primary peritoneal and fallopian tube cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of intraperitoneal administration of an Edmonston's strain measles virus genetically engineered to produce sodium iodine symporter (NIS) (measles virus \[MV\]-NIS) in patients with recurrent ovarian cancer, delivered by adipose tissue derived mesenchymal stem cells (MSC). (Phase I) II. To assess the 12 month overall survival of patients treated with this regimen. (Phase II) SECONDARY OBJECTIVES: I. To assess the tolerability of this regimen. (Phase II) II. To assess the 4 month progression free survival of patients treated with this regimen. (Phase II) III. To assess the response rate, progression-free survival, and overall survival of patients treated with this regimen. (Phase II) TRANSLATIONAL OBJECTIVES: I. To assess 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 versus MSC delivered MV-NIS using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging. (Phase II) II. To assess viremia, viral replication, and measles virus shedding/persistence following intraperitoneal administration. (Phase II) III. To assess humoral and cellular immune response to the injected virus. (Phase II) IV. To assess in a preliminary fashion the development of antitumor immune response. (Phase II) OUTLINE: This is a phase I, dose-escalation study followed by phase II study. Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter intraperitoneally (IP) over 30 minutes on day 1 of cycle 1 and MV-NIS infected mesenchymal stem cells (MSC) (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed up every 6 months for up to 5 years.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
Given IP
Given IP
PROCEDUREEchocardiography
Undergo ECHO
PROCEDUREMultigated Acquisition Scan
Undergo MUGA
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREChest Radiography
Undergo chest X-ray
Undergo SPECT/CT
PROCEDUREComputed Tomography
Undergo CT
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
Sponsors
Mayo Clinic
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have: * Recurrent or progressive ovarian cancer, primary peritoneal cancer or fallopian tube cancer after prior treatment with platinum and taxanes * Histologic confirmation of the original primary tumor * Prior bilateral oophorectomy * The following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified (NOS) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 * Absolute neutrophil count (ANC) \>= 1500/uL (obtained =\< 7 days prior to registration) * Platelet (PLT) \>= 100,000/uL (obtained =\< 7 days prior to registration) * Total bilirubin =\< upper normal limit (obtained =\< 7 days prior to registration) * Aspartate aminotransferase (AST) =\< 2 x upper limit of normal (ULN) (obtained =\< 7 days prior to registration) * Creatinine =\< 1.5 x ULN (obtained =\< 7 days prior to registration) * Hemoglobin (Hgb) \>= 9.0 g/dL (obtained =\< 7 days prior to registration) * Normal cardiac function as defined by a normal ejection fraction by MUGA (multi gated acquisition scan) or echocardiogram * Provide informed written consent * Willing to return to Mayo Clinic Rochester for follow-up * Life expectancy \>= 12 weeks * Willing to provide all biologic specimens as required by the protocol * Measurable disease by exam or CT scan, or for patients with cancer antigen (CA)-125 elevation or with microscopic residual but without measurable disease on imaging, willingness to undergo laparoscopy for evaluation of treatment effect if no radiographic progression after 6 treatment cycles * CD4 count \>= 200/uL or \>= 15% of peripheral blood lymphocytes
Exclusion criteria
* Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of the ovary * Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy; subjects will be excluded if this is their first relapse and they have recurred \> 6 months from completion of primary (adjuvant) chemotherapy * Active infection =\< 5 days prior to registration * History of tuberculosis or history of tuberculosis skin test purified protein derivative (PPD) positivity * History of other malignancy =\< 5 years prior to registration except for non-melanoma skin cancer, carcinoma in situ of the cervix, and ductal carcinoma in situ (DCIS) * 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 * Extensive abdominal surgery if it includes enterotomy(ies) =\< 3 weeks prior to registration; this criterion does not apply to placement of the peritoneal Port-A-Cath or lysis of adhesions at the time of registration * Any viral or gene therapy prior to registration * Radiation therapy to the abdomen or pelvis * 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 \[SVT\]) * Other cardiac or pulmonary disease that, at the investigators discretion, can impair treatment safety * 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) * Intra-abdominal disease \> 8 cm in diameter at the time of registration, intrahepatic disease, or disease beyond the abdominal cavity; patients with intra-abdominal lymph node involvement are eligible based on biodistribution data indicating viral dissemination to lymph nodes following intraperitoneal administration * 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 * Allergy to iodine; this does not include reactions to intravenous contrast materials * Any other pathology or condition where the principle investigator may deem to negatively impact treatment safety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Count of Participants That Experience a DLT | 28 days | Maximum tolerated dose will be defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients). |
| Overall Survival at 12 Months | 12 months | The proportion of patients that were followed and alive at 12 months post registration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response | 5 years | A confirmed tumor response is defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. CR(complete response) is determined by the disappearance of all target lesions and normalization of CA125 if elevated at baseline. PR(partial response) is determined by at least 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum LD. |
| 4 Month Progression Free Survival Rate | 4 months | Defined as the proportion of patients alive and progression free at 4 months. |
| Overall Survival (Phase II) | Up to 5 years | Defined as the length of time from study registration to date of death due to any cause. The distribution of survival time will be estimated using Kaplan-Meier survival curves and logrank tests. |
| Progression Free Survival (Phase II) | Up to 5 years | Progression-free survival (PFS) is defined as the length of time from study registration to the first of either death due to any cause or progression. The distribution of PFS will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall PFS in patients treated with MV-NIS/MSC will be made to patients enrolled on the prior MV-CEA and MV-NIS trial in an exploratory manner. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREvanthia Galanis, MD
Mayo Clinic
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I Dose Level 0 Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and 10\^7 MV-NIS infected MSC (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or MRI throughout the study. | 3 |
| Phase I Dose Level 1 Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and 10\^8 MV-NIS infected MSC (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or MRI throughout the study. | 6 |
| Phase II (Dose Level 1) Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1 of cycle 1 and 10\^8 MV-NIS infected MSC (if MSC are not available, MV-NIS may be given alone) IP over 30 minutes of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO or MUGA prior to registration and blood sample collection, chest X-ray, SPECT/CT, CT or MRI throughout the study. | 20 |
| Total | 29 |
Baseline characteristics
| Characteristic | Phase I Dose Level 0 | Phase I Dose Level 1 | Phase II (Dose Level 1) | Total |
|---|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 12.74 | 62.3 years STANDARD_DEVIATION 9.11 | 62.5 years STANDARD_DEVIATION 8.94 | 62.1 years STANDARD_DEVIATION 9.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 6 Participants | 18 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 18 Participants | 26 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 20 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 5 / 7 | 14 / 23 |
| other Total, other adverse events | 4 / 4 | 6 / 7 | 20 / 23 |
| serious Total, serious adverse events | 0 / 4 | 0 / 7 | 4 / 23 |
Outcome results
Primary
Count of Participants That Experience a DLT
Maximum tolerated dose will be defined as the dose level below the lowest dose that induces dose-limiting toxicity (DLT) in at least one-third of patients (at least 2 of a maximum of 6 new patients).
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase I Dose Level 0 | Count of Participants That Experience a DLT | 0 Participants |
| Phase I Dose Level 1 | Count of Participants That Experience a DLT | 0 Participants |
Primary
Overall Survival at 12 Months
The proportion of patients that were followed and alive at 12 months post registration.
Time frame: 12 months
Population: Both Phase I and Phase II patients treated at dose level 1 are evaluable for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Dose Level 0 | Overall Survival at 12 Months | 0.692 Proportion of patients |
Secondary
4 Month Progression Free Survival Rate
Defined as the proportion of patients alive and progression free at 4 months.
Time frame: 4 months
Population: All evaluable patients treated at the maximum tolerated dose(Dose level 1) will be included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I Dose Level 0 | 4 Month Progression Free Survival Rate | 0.769 proportion of patients |
Secondary
Overall Survival (Phase II)
Defined as the length of time from study registration to date of death due to any cause. The distribution of survival time will be estimated using Kaplan-Meier survival curves and logrank tests.
Time frame: Up to 5 years
Secondary
Progression Free Survival (Phase II)
Progression-free survival (PFS) is defined as the length of time from study registration to the first of either death due to any cause or progression. The distribution of PFS will be estimated using Kaplan-Meier survival curves and logrank tests. In addition, comparisons of overall PFS in patients treated with MV-NIS/MSC will be made to patients enrolled on the prior MV-CEA and MV-NIS trial in an exploratory manner.
Time frame: Up to 5 years
Secondary
Tumor Response (Phase II)
Will be defined as complete response or partial response.
Time frame: Up to 5 years
Other Pre-specified
Antitumor Immune Response (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Cellular Immune Response to the Injected Virus (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Humoral Immune Response to the Injected Virus (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Incidence of Viral Replication (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Incidence of Viremia (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Measles Virus Shedding/Persistence Following Intraperitoneal Administration (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Time Course of Viral Gene Expression (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years
Other Pre-specified
Virus Elimination and Biodistribution of Virally Infected Cells by Single Photon Emission Computed Tomography Imaging (Phase II)
Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out using Spearman's coefficients, chi squared tests, Wilcoxon rank-sum tests, Kaplan-Meier curves, and Cox proportional hazards models, where appropriate.
Time frame: Up to 5 years