Clinical trial NCT02068794: MV-NIS Infected Mesenchymal Stem Cells in Treating Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer
Official title: Phase I/II Trial of Intraperitoneal Administration of Adipose Tissue Derived Mesenchymal Stem Cells Infected With a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-02-21
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) (Phase I)
timeFrame: 28 days
measure: Number and severity of adverse events (Phase I)
timeFrame: Up to 5 years
measure: Overall toxicity incidence (Phase I)
timeFrame: Up to 5 years
measure: Toxicity profiles by dose level and patient (Phase I)
timeFrame: 28 days
measure: Proportion of patients alive at 12 months (Phase II)
timeFrame: At 12 months after study registration
Secondary outcomes:
measure: Tumor response (Phase II)
timeFrame: Up to 5 years
measure: Rate of progression free survival (Phase II)
timeFrame: Length of time from study registration to the first of either death due to any cause or progression, assessed at 4 months
measure: Overall survival (Phase II)
timeFrame: Length of time from study registration to date of death due to any cause or last follow up assessed up to 5 years
measure: Progression free survival (Phase II)
timeFrame: Length of time from study registration to the first of either death due to any cause or progression assessed at 5 years
measure: Maximum grade for each type of toxicity (Phase II)
timeFrame: Up to 5 years
Other outcomes:
measure: Time course of viral gene expression (Phase II)
timeFrame: Up to 5 years
measure: Virus elimination and biodistribution of virally infected cells by single photon emission computed tomography imaging (Phase II)
timeFrame: Up to 5 years
measure: Incidence of viremia (Phase II)
timeFrame: Up to 5 years
measure: Incidence of viral replication (Phase II)
timeFrame: Up to 5 years
measure: Measles virus shedding/persistence following intraperitoneal administration (Phase II)
timeFrame: Up to 5 years
measure: Humoral immune response to the injected virus (Phase II)
timeFrame: Up to 5 years
measure: Cellular immune response to the injected virus (Phase II)
timeFrame: Up to 5 years
measure: Antitumor immune response (Phase II)
timeFrame: Up to 5 years
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Evanthia Galanis, MD
role: PRINCIPAL_INVESTIGATOR
References: