Clinical Trials /

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

NCT02364713

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MC1365
  • SECONDARY ID: NCI-2015-00133
  • SECONDARY ID: MC1365
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02364713

Conditions

  • 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

Interventions

DrugSynonymsArms
Gemcitabine HydrochloridedFdCyd, Difluorodeoxycytidine Hydrochloride, Gemzar, LY-188011, LY188011Arm B (DOXIL, GEM, TOPA, TAXOL)
Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide SymporterMV-NISArm A (MV-NIS)
PaclitaxelAnzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol KonzentratArm B (DOXIL, GEM, TOPA, TAXOL)
Pegylated Liposomal Doxorubicin HydrochlorideATI-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-99Arm B (DOXIL, GEM, TOPA, TAXOL)
Topotecan HydrochlorideHycamptamine, Hycamtin, SKF S-104864-A, Topotecan HCl, topotecan hydrochloride (oral)Arm B (DOXIL, GEM, TOPA, TAXOL)

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (MV-NIS)ExperimentalPatients 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.
    Arm B (DOXIL, GEM, TOPA, TAXOL)Active ComparatorPatients 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.
    • Gemcitabine Hydrochloride
    • Paclitaxel
    • Pegylated Liposomal Doxorubicin Hydrochloride
    • Topotecan Hydrochloride

    Eligibility 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
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall survival
    Time Frame:Time from registration/randomization to death due to all causes, assessed up to 10 years
    Safety Issue:
    Description: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

    Measure:Incidence of adverse events per Common Terminology Criteria for Adverse Events version 4.0
    Time Frame:Up to 10 years
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description:Objective response rates will be compared between treatment arms using chi-square or fisher exact methodology as appropriate.
    Measure:Overall survival
    Time Frame:At 12 months
    Safety Issue:
    Description: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.
    Measure: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
    Safety Issue:
    Description: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.
    Measure:Progression-free survival
    Time Frame:At 6 months
    Safety Issue:
    Description: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.
    Measure:Quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian questionnaire
    Time Frame:Up to 10 years
    Safety Issue:
    Description: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

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Mayo Clinic

    Last Updated

    April 19, 2017