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

MC1365, 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

INTRODUCTION

  • Org Study ID: MC1365
  • Secondary ID: NCI-2015-00133, MC1365, P30CA015083
  • NTC ID: NCT02364713
  • Sponsor: 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.

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.

  • Overall Status
    Recruiting
  • Start Date
    March 13, 2015
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Overall survival

Primary Outcome 1 - Timeframe: Time from registration/randomization to death due to all causes, assessed up to 5 years

CONDITION

  • 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

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 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 for up to 7 days

Gender: Female

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Evanthia Galanis

Role: Principal Investigator

Affiliation: Mayo Clinic in Rochester

Overall Contact

Name: Evanthia Galanis

Phone: N/A

Email: N/A

LOCATION

Facility Status Contact
Facility: Mayo Clinic in Arizona
Scottsdale, Arizona 85259
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office
855-776-0015
mayocliniccancerstudies@mayo.edu
Facility: Mayo Clinic in Florida
Jacksonville, Florida 32224-9980
United States
Status: Recruiting Contact: Principal Investigator
John K. Camoriano
855-776-0015
mayocliniccancerstudies@mayo.edu
Facility: Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Status: Recruiting Contact: Contact
Clinical Trials Referral Office
855-776-0015
mayocliniccancerstudies@mayo.edu