Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02364713
Recruitment Status : Recruiting
First Posted : February 18, 2015
Last Update Posted : October 26, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Fallopian Tube Transitional Cell Carcinoma Malignant Ovarian Clear Cell Tumor Malignant Ovarian Endometrioid Tumor Malignant Ovarian Serous Tumor Ovarian Seromucinous Carcinoma Ovarian Transitional Cell Carcinoma Primary Peritoneal Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter Drug: Paclitaxel Drug: Pegylated Liposomal Doxorubicin Hydrochloride Other: Quality-of-Life Assessment Drug: Topotecan Hydrochloride Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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.

TERTIARY 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. Courses 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of a Genetically Engineered NIS-Expressing Strain of Measles Virus Versus Investigator's Choice Chemotherapy for Patients With Platinum-Resistant Ovarian, Fallopian, or Peritoneal Cancer
Actual Study Start Date : March 13, 2015
Estimated Primary Completion Date : February 2025
Estimated Study Completion Date : February 2025


Arm Intervention/treatment
Experimental: Arm A (MV-NIS)
Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter IP over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Given IP
Other Name: MV-NIS

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Active Comparator: 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. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Gemcitabine Hydrochloride
Given IV
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Drug: Pegylated Liposomal Doxorubicin Hydrochloride
Given IV
Other Names:
  • ATI-0918
  • Caelyx
  • DOX-SL
  • Doxil
  • Doxilen
  • Doxorubicin HCl Liposome
  • Doxorubicin Hydrochloride Liposome
  • Duomeisu
  • Evacet
  • LipoDox
  • Liposomal Adriamycin
  • Liposomal Doxorubicin Hydrochloride
  • Liposomal-Encapsulated Doxorubicin
  • Pegylated Doxorubicin HCl Liposome
  • S-Liposomal Doxorubicin
  • Stealth Liposomal Doxorubicin
  • TLC D-99

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)




Primary Outcome Measures :
  1. Overall survival [ Time Frame: Time from registration/randomization to death due to all causes, assessed up to 10 years ]
    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 Outcome Measures :
  1. Incidence of adverse events per Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 10 years ]
    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 using Chi-Square tests.

  2. Objective response rates 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: Up to 10 years ]
    Objective response rates will be compared between treatment arms using chi-square or fisher exact methodology as appropriate.

  3. Overall survival [ Time Frame: At 12 months ]
    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.

  4. Progression-free survival [ Time Frame: Time from start of study therapy to the date of first observation of disease progression or death due to any cause (whichever comes first), assessed up to 10 years ]
    The distribution of progression-free survival for both arms of the study will be estimated using the Kaplan-Meier method, and be compared using a one-sided logrank test.

  5. Progression-free survival [ Time Frame: At 6 months ]
    Progression-free survival at 6 months distributions both arms of the study will be estimated using the Kaplan-Meier method, and be compared using a one-sided logrank test.

  6. Quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian questionnaire [ Time Frame: Up to 10 years ]
    Quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian 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. Generalized linear mixed models that incorporate main effects of treatment arm, time and interaction of arm and time will be applied to analyze the longitudinal data of quality of life. Population-level and subject-level longitudinal plots will be plotted to display the trend of patient r


Other Outcome Measures:
  1. Changes in anti-ovarian cancer immune responses in both treatment arms [ Time Frame: Baseline to up to 10 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).

  2. Gene expression profile predictive of therapeutic response to oncolytic measles virus encoding thyroidal sodium iodide symporter [ Time Frame: Up to 10 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).

  3. Humoral and cellular immune responses to oncolytic measles virus encoding thyroidal sodium iodide symporter [ Time Frame: Up to 10 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).

  4. Time course of viral gene expression and virus elimination and biodistribution of virally infected cells using single-photon emission computerized tomography/computed tomography imaging [ Time Frame: 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).

  5. Viremia, viral replication, and viral shedding/persistence following intraperitoneal administration within the oncolytic measles virus encoding thyroidal sodium iodide symporter treatment arm [ Time Frame: Up to 10 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • PRE-REGISTRATION INCLUSION CRITERIA:
  • Ability to understand and the willingness to sign a written informed consent document
  • 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
  • Platelet (PLT) >= 100,000/uL
  • Total bilirubin =< ULN
  • Aspartate aminotransferase (AST) =< 2 x ULN
  • Creatinine =< 1.5 x ULN
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • 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 physical exam or CT scan, 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) within 1 month of 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 EXCLUSION CRITERIA:
  • Epithelial tumors of low malignant potential, stromal tumors, and germ cell tumors of the ovary
  • Evidence of measurable disease (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]) outside of the peritoneal cavity (ex: mediastinal lymphadenopathy, parenchymal liver metastasis, or symptomatic pleural effusion proven or suspected to be due to cancer)

    • Note: Asymptomatic pleural effusion with or without minimal pleural involvement as long as there is no measurable disease outside the peritoneum/retroperitoneum is allowed
  • Bulky metastases, defined as any tumor nodule or lymph nodes > 5 cm in greatest dimension on axial images on pre-treatment CT, PET/CT, or magnetic resonance imaging (MRI)

    • Note: patients with bulky (> 5 cm) disease for whom gross total cytoreduction is deemed feasible by a surgeon (with confirmation by a second surgeon after radiologic review) are eligible for participation in the context of cytoreductive surgery
  • Resistant to all of the following: DOXIL, gemcitabine hydrochloride (GEM), topotecan hydrochloride (TOPA), and weekly paclitaxel (TAXOL); (NOTE: resistance is defined as either 1) less than a complete response to any chemotherapy regimen containing the agent in question [consider weekly TAXOL as a separate agent from every-three-week TAXOL], 2) serum CA-125 >= 2 x ULN within 180 days of last dose of chemotherapy containing the agent in question, confirmed by a second CA-125 [the second CA-125 does not have to be within 180 days of chemotherapy], or 3) CT or PET/CT evidence of cancer recurrence/progression within 180 days of last dose of chemotherapy containing the agent in question; [for example, if a patient previously received carboplatin and GEM, had a complete response, and had initial evidence of relapse > 180 days after the last dose of GEM, that patient would not be considered resistant to GEM])
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4
  • 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)
  • Active infection =< 7 days prior to study entry
  • Any of the following prior therapies:

    • Chemotherapy =< 3 weeks prior to study entry
    • Immunotherapy =< 4 weeks prior to study entry
    • Biologic therapy =< 4 weeks prior to study entry
    • Extensive abdominal surgery if it includes enterotomy(ies) =< 3 weeks prior to study entry; (NOTE: this criterion does not apply to placement of the peritoneal Port-A-Cath or lysis of adhesions at the time of study entry)
    • Any viral or gene therapy prior to study entry
  • Failure to recover to =< grade 1 from acute, reversible effects of prior chemotherapy, excluding alopecia regardless of interval since last treatment; (NOTE: patients with residual peripheral neuropathy are allowed)
  • New York Heart Association classification III or IV congestive heart failure, known symptomatic coronary artery disease, 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 investigator's discretion, can impair treatment safety
  • 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)
  • Any concurrent medications which could interfere with the trial
  • History of tuberculosis or history of purified protein derivative (PPD) positivity
  • Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids or steroids given for the purpose of adrenal replacement given at physiologic doses
  • 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; (NOTE: this does not include reactions to intravenous contrast materials)
  • Any other pathology or condition which the principal investigator may deem to negatively impact treatment safety
  • On anticoagulation and unable to discontinue temporarily

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02364713


Locations
Layout table for location information
United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: John K. Camoriano, M.D.         
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Gerardo Colon-Otero, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Evanthia Galanis, M.D.         
Sub-Investigator: Matthew S. Block, M.D.         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Evanthia Galanis Mayo Clinic

Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02364713     History of Changes
Other Study ID Numbers: MC1365
NCI-2015-00133 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1365 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 18, 2015    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Transitional Cell
Fallopian Tube Neoplasms
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Paclitaxel
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Topotecan
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents