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Brief Title: MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

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

INTRODUCTION

  • Org Study ID: MC1266
  • Secondary ID: NCI-2014-00016, MC1266, P30CA015083, P50CA136393, P50CA083639
  • NTC ID: NCT02068794
  • Sponsor: Mayo Clinic

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.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

  • Overall Status
    Recruiting
  • Start Date
    March 31, 2014
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Maximum tolerated dose (MTD) (Phase I)

Primary Outcome 1 - Timeframe: 28 days

Primary Outcome 2 - Measure: Number and severity of adverse events (Phase I)

Primary Outcome 2 - Timeframe: Up to 5 years

Primary Outcome 3 - Measure: Overall toxicity incidence (Phase I)

Primary Outcome 3 - Timeframe: Up to 5 years

Primary Outcome 4 - Measure: Toxicity profiles by dose level and patient (Phase I)

Primary Outcome 4 - Timeframe: 28 days

Primary Outcome 5 - Measure: Proportion of patients alive at 12 months (Phase II)

Primary Outcome 5 - Timeframe: At 12 months after study registration

CONDITION

  • 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

ELIGIBILITY

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 multi gated acquisition scan (MUGA) 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Evanthia Galanis

Role: Principal Investigator

Affiliation: Mayo Clinic

Overall Contact

Name: Evanthia Galanis

Phone: N/A

Email: N/A

LOCATION

Facility Status Contact
Facility: Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office
855-776-0015
mayocliniccancerstudies@mayo.edu