Fallopian Tube Carcinosarcoma, 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, Ovarian Carcinosarcoma, Ovarian Clear Cell Adenocarcinoma, Ovarian Endometrioid Adenocarcinoma, Ovarian Mucinous Adenocarcinoma, Ovarian Seromucinous Carcinoma, Ovarian Serous Adenocarcinoma, Ovarian Transitional Cell Carcinoma, Ovarian Undifferentiated Carcinoma, Platinum-Resistant Fallopian Tube Carcinoma, Platinum-Resistant Ovarian Carcinoma, Platinum-Resistant Primary Peritoneal Carcinoma, Primary Peritoneal Carcinosarcoma, Primary Peritoneal Clear Cell Adenocarcinoma, Primary Peritoneal Endometrioid Adenocarcinoma, Primary Peritoneal Serous Adenocarcinoma, Primary Peritoneal Transitional Cell Carcinoma, Primary Peritoneal Undifferentiated Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Conditions
Brief summary
This randomized phase II trial studies how well oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) compared to investigator's choice chemotherapy works in treating patients with ovarian, fallopian, or peritoneal cancer. Measles virus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.
Detailed description
PRIMARY OBJECTIVE: I. Compare clinical efficacy of Arm A (MV-NIS therapy) and Arm B (standard cytotoxic chemotherapy), as measured by overall survival (OS). SECONDARY OBJECTIVES: I. Compare progression-free survival (PFS), overall survival at 12 months (OS12), progression-free survival at six months (PFS6), and objective response rate (ORR) between MV-NIS therapy and standard chemotherapy. II. Assess safety and tolerability of MV-NIS, and compare with standard chemotherapy. III. Compare quality of life as assessed by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) between MV-NIS and standard chemotherapy. TRANSLATIONAL OBJECTIVES: I. 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 using single-photon emission computerized tomography (SPECT)/computed tomography (CT) imaging within the MV-NIS treatment arm. II. Assess viremia, viral replication, and viral shedding/persistence following intraperitoneal administration within the NV-NIS treatment arm. III. Measure humoral and cellular immune responses to MV-NIS within the NV-NIS treatment arm. IV. Measure changes in anti-ovarian cancer (OC) immune responses in both treatment arms. V. Perform transcriptomic analysis on tumor biopsy specimens to determine a gene expression profile predictive of therapeutic response to MV-NIS. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter intraperitoneally (IP) over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 1 hour on day 1, or gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15, or paclitaxel IV over 1 hour on days 1, 8, and 15. Patients may also receive bevacizumab IV over 30-90 minutes on days 1 and 15 with pegylated liposomal doxorubicin hydrochloride, topotecan hydrochloride, or paclitaxel. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for 5 years.
Interventions
Given IV
Given IV
Correlative studies
Given IP
Given IV
Given IV
Ancillary studies
Given IV
Sponsors
Study design
Eligibility
Inclusion criteria
* PRE-REGISTRATION INCLUSION CRITERIA: * Ability to understand and the willingness to sign a written informed consent document * The effects of the candidate chemoprevention agents on the developing human fetus remain incompletely defined; however, study participants will be women who have gone through a bi-lateral oophorectomy procedure * Willingness to be evaluated for surgical placement of an intraperitoneal port and undergo biopsy if feasible for a research sample * REGISTRATION/RANDOMIZATION INCLUSION CRITERIA: * Recurrent, persistent, or progressive epithelial ovarian, fallopian tube, or primary peritoneal cancer after treatment with bilateral oophorectomy and either cisplatin or carboplatin and either paclitaxel, albumin-bound paclitaxel, or docetaxel; histologic confirmation of the primary tumor is required; eligible histologies include serous, endometrioid, clear cell, mucinous, transitional cell, undifferentiated, or mixed carcinoma * Platinum-resistant or platinum-refractory disease, defined as either 1) less than a complete response to the most recent carboplatin- or cisplatin-containing chemotherapy regimen, 2) serum cancer antigen (CA)-125 \>= 2 x upper limit of normal (ULN) within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy, confirmed by a second CA-125 (the second CA-125 does not have to be within 180 days of chemotherapy), or 3) CT or positron emission tomography (PET)/CT evidence of cancer recurrence within 180 days of last dose of carboplatin- or cisplatin-containing chemotherapy * 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 =\< ULN (obtained =\< 7 days prior to registration) * Aspartate aminotransferase (AST) =\< 2 x 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) * Willingness to return to Mayo Clinic Rochester or another participating institution for follow-up; patients who are randomized to Arm B (cytotoxic chemotherapy) may receive chemotherapy at any oncology clinic able to provide the protocol-directed therapy and willing to send laboratory data to the participating institution; however, patients must be willing to return to the participating institution every two months for evaluation; patients who are randomized to Arm A must be willing to receive all treatment and follow-up at a participating institution * Life expectancy \>= 12 weeks * Willingness to provide all biologic specimens as required by the protocol * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, or evaluable disease by CA-125; (NOTE: CA-125-evaluable disease is defined as serum CA-125 \>= 2 x ULN that is determined by the treating clinician to be due to recurrent ovarian, fallopian tube, or primary peritoneal cancer) * Normal cardiac function, as determined by left ventricular ejection fraction (LVEF) \>= institutional lower limit of normal on echocardiogram or multi-gated acquisition scan (MUGA) =\< 1 month prior to registration * If liposomal doxorubicin hydrochloride (DOXIL) is selected as the investigator's choice chemotherapy: * Lifetime exposure to doxorubicin =\< 240 mg/m\^2 (or equivalent biologic dose if prior exposure to a different anthracycline) * Candidate for surgical placement of an intraperitoneal port, as determined by a gynecologic oncology surgeon * Must have anti-measles immunity as demonstrated by serum immunoglobulin (Ig)G anti-measles antibody levels of \>= 1.1 EU/ml as determined by BioPlex Measles IgG multiplex flow immunoassay
Exclusion criteria
* REGISTRATION/RANDOMIZATION
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 5 years | Defined as the time from registration/randomization to death due to all causes. Will be a comparison of the oncolytic measles virus encoding thyroidal sodium iodide symporter versus investigator's choice chemotherapy using a one-sided log-rank test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 11 months | Defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause (whichever comes first). The distribution of progression-free survival for both arms of the study will be estimated using the Kaplan-Meier method. |
| Overall Survival | 12 months | Defined as the time from registration/randomization to death due to all causes. Overall survival at 12 months distributions both arms of the study will be estimated using the Kaplan-Meier method and be compared using a one-sided logrank test. |
| Objective Response Rate | 11 months | Objective response rate is defined to be a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart |
| Incidence of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0 | 12 months | Safety and tolerability of the oncolytic measles virus encoding thyroidal sodium iodide symporter as compared to standard therapy will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event rates for grade 3 or higher adverse events will be compared between arms. |
| Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Ovarian Questionnaire | 5 years | Quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire will be compared between treatment arms. The assessment will be scored according to the assessment scoring algorithm at each collection time. Scores at end of each cycle will be compared using Wilcoxon procedures. The FACT-O consist of 39 questions, each answered on a 5-point Likert scale ranging from 0 (Not at all) to 4 (Very much). Possible total scores range from 0-156, with higher scores indicating better quality of life. We will calculate the mean change from the start to the end of the study of patient total FACT-O point sum by arm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Viremia, Viral Replication, and Viral Shedding/Persistence Following Intraperitoneal Administration Within the Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter Treatment Arm | Up to 5 years | Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). |
| Humoral and Cellular Immune Responses to Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter | Up to 5 years | Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). |
| Changes in Anti-ovarian Cancer Immune Responses in Both Treatment Arms | Baseline to up to 5 years | Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). |
| Gene Expression Profile Predictive of Therapeutic Response to Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter | Up to 5 years | Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). |
| Time Course of Viral Gene Expression and Virus Elimination and Biodistribution of Virally Infected Cells Using Single-photon Emission Computerized Tomography/Computed Tomography Imaging | Up to course 2 | Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (MV-NIS) Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter: Given IP\>
\> Quality-of-Life Assessment: Ancillary studies | 10 |
| Arm B (DOXIL, GEM, TOPA, TAXOL) Patients receive pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15, or topotecan hydrochloride IV over 30 minutes on days 1, 8, and 15, or paclitaxel IV over 1 hour on days 1, 8, and 15. Patients may also receive bevacizumab IV over 30-90 minutes on days 1 and 15 with pegylated liposomal doxorubicin hydrochloride, topotecan hydrochloride, or paclitaxel. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.\>
\> Bevacizumab: Given IV\>
\> Gemcitabine Hydrochloride: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Paclitaxel: Given IV\>
\> Pegylated Liposomal Doxorubicin Hydrochloride: Given IV\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> Topotecan Hydrochloride: Given IV | 7 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 2 | 2 |
Baseline characteristics
| Characteristic | Arm B (DOXIL, GEM, TOPA, TAXOL) | Total | Arm A (MV-NIS) |
|---|---|---|---|
| Age, Continuous | 64 years | 67 years | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 13 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 10 | 5 / 7 |
| other Total, other adverse events | 8 / 9 | 4 / 5 |
| serious Total, serious adverse events | 6 / 9 | 2 / 5 |
Outcome results
Overall Survival
Defined as the time from registration/randomization to death due to all causes. Will be a comparison of the oncolytic measles virus encoding thyroidal sodium iodide symporter versus investigator's choice chemotherapy using a one-sided log-rank test.
Time frame: 5 years
Population: All eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (MV-NIS) | Overall Survival | 11.2 Months |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Overall Survival | 14.2 Months |
Incidence of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0
Safety and tolerability of the oncolytic measles virus encoding thyroidal sodium iodide symporter as compared to standard therapy will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event rates for grade 3 or higher adverse events will be compared between arms.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MV-NIS) | Incidence of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0 | 3 Participants |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Incidence of Adverse Events Per Common Terminology Criteria for Adverse Events Version 4.0 | 2 Participants |
Objective Response Rate
Objective response rate is defined to be a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart
Time frame: 11 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MV-NIS) | Objective Response Rate | 0 Participants |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Objective Response Rate | 0 Participants |
Overall Survival
Defined as the time from registration/randomization to death due to all causes. Overall survival at 12 months distributions both arms of the study will be estimated using the Kaplan-Meier method and be compared using a one-sided logrank test.
Time frame: 12 months
Population: All eligible and treated patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MV-NIS) | Overall Survival | 4 Participants |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Overall Survival | 2 Participants |
Progression-free Survival
Defined as the time from start of study therapy to the date of first observation of disease progression or death due to any cause (whichever comes first). The distribution of progression-free survival for both arms of the study will be estimated using the Kaplan-Meier method.
Time frame: 11 months
Population: All eligible and treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A (MV-NIS) | Progression-free Survival | 1.8 Months |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Progression-free Survival | 4.1 Months |
Progression-free Survival
Progression-free survival at 6 months distributions both arms of the study will be estimated using the Kaplan-Meier method.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MV-NIS) | Progression-free Survival | 5 Participants |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Progression-free Survival | 4 Participants |
Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Ovarian Questionnaire
Quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) questionnaire will be compared between treatment arms. The assessment will be scored according to the assessment scoring algorithm at each collection time. Scores at end of each cycle will be compared using Wilcoxon procedures. The FACT-O consist of 39 questions, each answered on a 5-point Likert scale ranging from 0 (Not at all) to 4 (Very much). Possible total scores range from 0-156, with higher scores indicating better quality of life. We will calculate the mean change from the start to the end of the study of patient total FACT-O point sum by arm.
Time frame: 5 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A (MV-NIS) | Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Ovarian Questionnaire | 5.2 change in score | Standard Deviation 14.6 |
| Arm B (DOXIL, GEM, TOPA, TAXOL) | Quality of Life as Measured by the Functional Assessment of Cancer Therapy-Ovarian Questionnaire | -12.6 change in score | Standard Deviation 12.1 |
Changes in Anti-ovarian Cancer Immune Responses in Both Treatment Arms
Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Baseline to up to 5 years
Gene Expression Profile Predictive of Therapeutic Response to Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Up to 5 years
Humoral and Cellular Immune Responses to Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Up to 5 years
Time Course of Viral Gene Expression and Virus Elimination and Biodistribution of Virally Infected Cells Using Single-photon Emission Computerized Tomography/Computed Tomography Imaging
Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Up to course 2
Viremia, Viral Replication, and Viral Shedding/Persistence Following Intraperitoneal Administration Within the Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter Treatment Arm
Descriptive statistics and simple scatter plots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
Time frame: Up to 5 years