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
Phase: PHASE2
Conditions: 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
Sponsor: Mayo Clinic

MC1365 
Protocol Version Date: 06Aug2020 
Mayo Clinic Cancer Center 
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 
 
Study Chair(s): 
 
 
 
 
 
 
 
Study Co-Chairs: 
 
 
 
 
 
 
 
 
 
 
 
 
 
Statisticians: 
 
 
 
†Study contributor(s) not responsible for patient care 
 
DCTD Supplied Investigational Agent(s): none 
 
 
Document History 
(Effective Date) 
 
 
 
Activation 
13 March 2015 
 
 
 
MCCC Add 1 
November 18, 2015 
 
 
 
MCCC Add 2 
March 18, 2016 
 
 
 
MCCC Add 3 
March 29, 2017 
 
 
 
MCCC Amdt 4 
April 20, 2018 
 
 
 
MCCC Amdt 5 
November 2, 2018 
 
 
 
MCCC Amdt 6 
February 5, 2019 
 
 
 
MCCC Amdt 7 
June 20, 2019 
 
 
 
MCCC Amdt 8 
September 11, 2020 
 
 
 
 
 

MC1365 
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Protocol Resources 
Questions: 
Contact Name: 
Patient eligibility*, test schedule, 
treatment delays/interruptions/adjustments, 
dose modifications, adverse events, 
forms completion and submission 
 
 
 
 
  
Forms completion and submission 
 
 
Protocol document, consent form, 
regulatory issues 
 
  
  
 
 
 
Serious Adverse Events  
  
 
 
Biospecimens issues 
 
 
  
 
  
*No waivers of eligibility per NCI  
 

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Table of Contents 
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 ........................................................................................ 1 
Protocol Resources.......................................................................................................................... 2 
Table of Contents ............................................................................................................................ 3 
Schema (non-bulky disease ≤5 cm) ................................................................................................ 4 
Schema (bulky disease >5 cm) ....................................................................................................... 5 
1.0 
Background ...................................................................................................................... 6 
2.0 
Goals............................................................................................................................... 10 
3.0 
Patient Eligibility............................................................................................................ 11 
4.0 
Test Schedule ................................................................................................................. 14 
5.0 
Stratification Factors ...................................................................................................... 19 
6.0 
Registration/Randomization Procedures ........................................................................ 19 
7.0 
Protocol Treatment ......................................................................................................... 22 
8.0 
Dosage Modification Based on Adverse Events ............................................................ 26 
9.0 
Ancillary Treatment ....................................................................................................... 27 
10.0 
Adverse Event (AE) Reporting and Monitoring......................................................... 29 
11.0 
Treatment Evaluation ................................................................................................. 32 
12.0 
Descriptive factors ...................................................................................................... 35 
13.0 
Treatment/ Follow-up Decision at Evaluation of Patient ........................................... 35 
14.0 
Pharmacologic/Correlative Studies ............................................................................ 37 
15.0 
Drug Information ........................................................................................................ 43 
16.0 
Statistical Considerations and Methodology .............................................................. 60 
17.0 
Pathology Considerations ........................................................................................... 64 
18.0 
Data Collection Procedures ........................................................................................ 65 
19.0 
Budget Considerations ................................................................................................ 66 
20.0 
References .................................................................................................................. 67 
Appendix I: ECOG PERFORMANCE STATUS ......................................................................... 69 
Appendix II: Patient Information Sheet ........................................................................................ 70 
Appendix III: FACT-O ................................................................................................................. 71 
Appendix IV: Prep and Storage of MV-NIS................................................................................. 74 
Appendix V: Arm Assignment Script for Bulky Disease ............................................................. 75 
 
 

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Schema (non-bulky disease ≤5 cm) 
Pre-registration (Informed Consent) 
 
 
 
Surgical evaluation 
 
 
 
Registration/randomization 
 
 
 
 
Arm A: MV-NIS 
Arm B: Cytotoxic Chemotherapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycle length = 28 days  
*Patients who develop PD but do not have progressive cancer-associated symptoms and are tolerating 
treatment well may continue therapy (either Arm) at the discretion of the treating investigator until 
additional progression is documented. 
†Bevacizumab may be added to liposomal doxorubicin, topotecan, or paclitaxel regimens as part of 
standard care 
Generic name or 
synonym 
Liposomal 
Doxorubicin 
Gemcitabine 
Topotecan 
Paclitaxel 
Bevacizumab 
NIS-Measles Virus 
(Edmonston 
Strain) 
Brand name 
Doxil 
Gemzar 
Hycamtin 
Taxol 
Avastin 
----- 
Mayo 
abbreviation 
PLD 
GEM 
TOPA 
TAXOL 
AVAST 
MV-NIS 
Availability 
Commercial 
Commercial 
Commercial Commercial 
Commercial 
Mayo Pharmacy 
 
Investigator’s choice of†: 
Liposomal Doxorubicin, 40 mg/m2; D1 of 28 
Or 
Gemcitabine, 1000 mg/m2; D1, D8, D15 of 28 
Or 
Topotecan, 4 mg/m2; D1, D8, D15 of 28 
Or 
Paclitaxel, 80 mg/m2; D1, D8, D15 of 28 
Intraperitoneal port placement 
Continue treatment*  
Monitor for toxicity (q28 days ±3 days) 
Monitor for PD (q56 days ±7 days) 
Event monitoring 
MV-NIS, 109 TCID 50 IP, D1 of 28 

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Schema (bulky disease >5 cm) 
Pre-registration (Informed Consent) 
 
 
 
Surgical evaluation (and radiology review by a second surgeon) 
 
 
 
Registration/blinded randomization 
 
 
 
Biopsy and debulking 
 
 
 
Unblinding of randomization in the OR 
 
 
 
 
Arm A: MV-NIS 
Arm B: Cytotoxic Chemotherapy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cycle length = 28 days  
*Patients who develop PD but do not have progressive cancer-associated symptoms and are tolerating 
treatment well may continue therapy (either arm) at the discretion of the treating investigator until 
additional progression is documented. 
†Bevacizumab may be added to liposomal doxorubicin, topotecan, or paclitaxel regimens as part of 
standard care
Investigator’s choice of: DOXIL, GEM, TAXOL, or 
TOPA† 
Intraperitoneal port placement 
Continue treatment * 
Monitor for toxicity (q28 days ±3 days) 
Monitor for PD (q56 days ±7 days) 
Event monitoring 
MV-NIS, 109 TCID 50 IP, D1 of 28 
Surgical closure (no IP port 
placement) 

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1.0 
Background 
1.1 
Ovarian, fallopian, and peritoneal cancer 
Ovarian cancer (along with fallopian and peritoneal cancer, collectively referred to as 
OC) is the second most common malignancy of the female genital tract in the United 
States. According to the American Cancer Society, there were an estimated 16,000 deaths 
in the United States in 2007 (1). Because there is no effective screening method for 
ovarian cancer, more than 70% of cases are diagnosed after the tumor has already spread 
beyond the ovaries. Although initial surgery and chemotherapy are often effective in 
inducing remission of OC, most patients will experience disease relapse despite initial 
treatment; 5-year survival with distant spread of OC is only 26.9% (2). 
Because most histologies of OC are initially sensitive to chemotherapy, patients with 
recurrent OC are frequently treated with cytotoxic therapy; however, OC ultimately 
becomes resistant or refractory to this form of treatment. Platinum-resistance, defined as 
an incomplete response to platinum-containing chemotherapy or OC progression within 
six months of receipt of platinum-containing chemotherapy, portends a poor prognosis 
and often is associated with a limited response to non-platinum-containing chemotherapy. 
Overall survival in platinum-resistant OC is often less than one year.  New therapies for 
platinum-resistant OC are badly needed. 
 
1.2 
Measles virus as cancer therapy 
The idea of using measles virus strains as anticancer therapy has emerged from the 
observation that natural measles infection can result in an antitumor effect. For example, 
natural infection with measles virus has been shown to lead to regression in patients with 
Hodgkin’s disease and non-Hodgkin’s lymphoma (3, 4). 
Measles virus is a negative strand, RNA virus, whose genome includes six protein 
products (5). Three of these proteins participate in the formation of the viral envelope; the 
H-protein is the surface glycoprotein which mediates measles virus attachment to its 
receptors, the CD46 molecule (6), the SLAM receptor (the latter being predominantly 
present on activated B and T cells) and the epithelial receptor nectin-4 (7). The F-protein 
is responsible for cell after viral attachment has taken place.  During natural infection 
with the measles virus, the virus replicates in susceptible tissues causing a very 
characteristic cytopathic effect, with development of multinucleated giant cells 
(syncytia). Cells infected by measles virus express F and H-proteins on their membranes 
and therefore become highly fusogenic. These cells can cause fusion not only with other 
infected cells but also with uninfected neighboring cells. Although wild type measles 
virus can lead to a potentially serious infectious disease, attenuated strains (vaccine 
strains) of measles virus have an excellent safety record and have resulted in significant 
decreases in measles incidence and mortality worldwide (8). 
In preclinical studies we showed that intratumoral or intravenous injection of a measles 
virus strain, deriving from the Edmonston vaccine lineage, can cause growth inhibition or 
total regression for a variety of established tumors and xenografts (9). 
Systemic use of an attenuated strain of measles virus as an anticancer agent can be 
potentially hampered by high levels of protecting anti-measles virus antibodies, which are 
present in more than 90% of the Western population as a result of immunization or 
natural infection (10). Ovarian cancer, however, provides us with a unique opportunity to 
exploit the antitumor potential of the vaccine strain of measles virus. In 85% of patients, 
ovarian cancer remains confined within the peritoneal cavity, providing an optimal 

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setting for viral delivery and direct virus-tumor interaction. 
MV strains have demonstrated potent antitumor activity against human epithelial ovarian 
cancer cells in vitro and in vivo. Most importantly, the virus was selectively oncolytic for 
ovarian tumor cells but caused minimal cytopathic damage on normal ovarian surface 
epithelium and normal mesothelium. This selectivity was in part mediated through 
overexpression of the measles virus receptor CD46 in ovarian cancer cells in contrast to 
low levels of expression in mesothelial cells and normal ovarian surface epithelial cells. 
When an MV derivative producing the human carcinoembryonic antigen (MV-CEA) was 
injected directly into established subcutaneous SKOV3ip.1 human epithelial ovarian 
xenografts in athymic mice, the virus induced complete regression of 80% of the tumors. 
Survival of mice bearing intraperitoneal tumors was significantly enhanced by virus 
therapy. The median survival of mice in the treated group was more than 80 days 
compared to 30 days for the control group. By day 48 post-implantation of cells, all mice 
in the control group had developed ascites and had to be euthanized. Similar data were 
subsequently obtained with MV-NIS (11, 12). Toxicology and biodistribution studies in 
measles virus infection susceptible Infarko CD46 Ge mice have demonstrated the safety of 
the approach (13). 
1.3 
Clinical experience with MV-NIS in ovarian cancer 
A phase I trial of intraperineal administration of MV-CEA has been completed (14). 21 
patients were treated with MV-CEA i.p. every four weeks for up to six cycles at ten 
different dose levels from 103 to 109 TCID50. We observed no dose-limiting toxicity, 
treatment induced immunosuppression, development of anti-CEA antibodies, increase in 
anti-CEA antibody titers or viral shedding in urine or saliva. Dose dependent CEA 
elevation in peritoneal fluid and serum was observed. Immunohistochemical analysis of 
patient tumor specimens revealed overexpression of measles virus receptor CD46 in 
13/15 patients. Best objective response was dose-dependent disease stabilization in 14/21 
patients with a median duration of 92.5 days (range 54 to 277 days). Five patients had 
significant decrease in CA-125 levels. Median survival of patients on study was 12.5 
months, (range 1.3 to 38.4 months) comparing favorably to an expected median survival 
of 6 months in this patient population. MV-NIS is an MV-Edmonston derivative, 
identical to MV-CEA except that it encodes the sodium iodine symporter (NIS) gene 
instead of the CEA gene (15). MV-NIS is at least as efficacious as MV-CEA in 
orthotopic ovarian cancer models (12)and it allows use of radioactive iodine isotopes for 
imaging (12) and treatment purposes.   
Six patients have been treated in 2 dose levels of MV-NIS (108 -109 TCID50), and an 
additional 10 patients at a 109 TCID50 dose expansion cohort for a total of 16 patients. 
No dose-limiting toxicity was observed. Most common cycle 1 toxicities included mild 
(grade 1-2) abdominal pain (8 patients); grade 1-2 fatigue (7 patients); and grade 1-2 
fever (3 patients). There was no treatment-induced immunosuppression as assessed by 
DTH, CD4, CD8, IgG and complement levels, no significant increase in the titers of MV 
antibodies in response to treatment and no viral shedding in urine or mouth gargle 
specimens. NIS expression in patient tumors following treatment was demonstrated in 
3 patients by 123I uptake on SPECT CTs and was associated with long progression-free 
survival. Study patients were heavily pretreated with a mean of 4.3 chemotherapy 
regimens at study entry (range 1-8). Median time to progression was 2.13 months (range 
0.8-32.5 + mo), and median overall survival 26.6 months (range 1.8-33.9 + mo); the latter 
compares favorably with outcomes in other contemporary series of novel therapeutics in 
recurrent platinum-resistant OC (6-12 months). In a pilot study to investigate the 
mechanism of these favorable outcomes, the development of antitumor immune response 

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in study patients was tested by performing pre- and post-treatment IFN-gamma and IL-4 
ELISPOT assays against insulin-like growth factor binding protein 2 (IGFBP2) and folate 
receptor alpha. In 3/4 patients, there was significant increase of anti-tumor specific T-
cells (p<0.05) suggesting that MV treatment of recurrent ovarian cancer patients can 
elicit cellular immune response against the patients’ tumor (16). 
1.4 
Liposomal doxorubicin in platinum-resistant ovarian cancer 
There are several chemotherapy regimens that demonstrated clinical efficacy in patients 
with platinum-resistant OC. Among these are liposomal doxorubicin (DOXIL), 
gemcitabine (GEM), topotecan (TOPA), and weekly paclitaxel (TAXOL). Each of these 
regimens is, therefore, a reasonable comparator for MV-NIS as therapy for platinum-
resistant OC. 
DOXIL has been approved by the FDA for use in OC patients whose cancer has 
progressed or recurred after platinum-based chemotherapy. Single-agent DOXIL was 
initially studied as a single-agent therapy for OC patients at 50 mg/m2 (17), but due to 
toxicity at this dose, DOXIL is generally given at 40 mg/m2 in clinical practice and as a 
standard in clinical trials (18). Common toxicities from DOXIL include hematologic 
toxicity (neutropenia and thrombocytopenia), palmar-plantar erythrodysesthesia (hand-
foot syndrome), and stomatitis. Median time to progression (TTP) and OS for patients 
treated with DOXIL in a phase III clinical trial were 16 weeks and 56 weeks, respectively 
(18). 
1.5 
Gemcitabine in platinum-resistant ovarian cancer 
GEM is an alternative to DOXIL that is also commonly used as a single agent therapy for 
platinum-resistant OC. GEM is also FDA-approved in combination with carboplatin for 
patients with platinum-sensitive OC. When used as a single agent in platinum-resistant 
OC in the context of a randomized phase III clinical trial, GEM was associated with 
neutropenia, anemia, and thrombocytopenia. Median time to progression (TTP) and OS 
for patients treated with DOXIL in a phase III clinical trial were 20 weeks and 51 weeks, 
respectively (18). 
1.6 
Topotecan in platinum-resistant ovarian cancer 
TOPA gained approval as a treatment for relapsed ovarian cancer based on a study 
comparing topotecan administered at 1.5 mg/m2 daily for 5 days. In this study, TOPA 
showed superiority to paclitaxel 175 mg/m2 in TTP (23 vs 14 weeks, P=0.002) (19). 
Because of the high rate of myelosuppression seen with the daily TOPA schedule in 
patients with relapsed ovarian cancer, investigators have studied alternative dosing 
schedules for single-agent topotecan. A prospective study evaluating patients receiving 
TOPA given weekly at 4 mg/m2 on Days 1, 8, and 15 of a 28 day cycle demonstrated 
good tolerability (20). A randomized phase II study compared daily TOPA with weekly 
TOPA, and this study showed that while clinical benefit rate and PFS slightly favored 
daily TOPA, OS was similar between daily and weekly TOPA (21). As a result, weekly 
TOPA is commonly used in patients with platinum-resistant OC. Hematologic toxicity is 
the most common dose-limiting side effect for TOPA. 
1.7 
Weekly paclitaxel in platinum-resistant ovarian cancer 
Because most patients with OC are initially treated with TAXOL and either carboplatin 
or cisplatin, many patients with platinum-resistant OC are also resistant to TAXOL. 
However, several studies have demonstrated objective tumor responses to weekly 
TAXOL even in TAXOL-resistant patients (22). This has led to the formal investigation 

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of weekly TAXOL in a multicenter phase II clinical trial (23). This study demonstrated a 
favorable toxicity profile, with peripheral neuropathy as the most common grade 3/4 
toxicity. PFS and OS with weekly TAXOL 80 mg/m2 are 6.1 and 10.43 months, 
respectively (22). 
1.8 
Bevacizumab in combination with chemotherapy for platinum-resistant ovarian cancer 
Multiple studies have demonstrated the clinical activity of bevacizumab in various 
clinical contexts of OC. In the AURELIA open-label randomized phase III trial, patients 
with platinum-resistant OC were assigned to treatment with chemotherapy alone 
(liposomal doxorubicin, topotecan, or weekly paclitaxel) or chemotherapy plus 
bevacizumab. The addition of bevacizumab led to an improvement in PFS from a median 
of 3.4 to 6.7 months, although the difference in OS was not deemed statistically 
significant (Ref PMID: 24637997). Based on this trial, bevacizumab is approved by the 
FDA for platinum-resistant OC at a dose of 10 mg/kg every 2 weeks in combination with 
liposomal doxorubicin, topotecan, or weekly paclitaxel. 
1.9a 
Surgery for recurrent ovarian cancer 
Secondary cytoreductive surgery is sometimes employed as a means of cancer control for 
patients with recurrent OC. While secondary cytoreduction is most commonly used in 
patients with platinum-sensitive recurrent OC, prospective randomized studies have not 
definitively identified which patients with recurrent OC benefit from secondary 
cytoreduction. For patients with platinum-resistant OC, secondary cytoreduction is 
infrequently offered, most often in a scenario in which the surgeon believes that a gross 
total cytoreduction is feasible without a high risk for major perioperative morbidity. 
1.9b 
Rationale for the study design 
Viral therapy with MV-NIS has demonstrated promising clinical activity in patients with 
platinum-resistant OC, with especially favorable survival demonstrated in patients with 
non-bulky disease. DOXIL, GEM, TOPA, and TAXOL are conventional chemotherapy 
options that are acceptable therapies commonly used in the setting of platinum-resistant 
OC, and selection of which of these regimens to use is often individualized based on prior 
chemotherapy exposure and toxicity. Given that the maximal benefit from MV-NIS 
therapy was in those patients with non-bulky disease, and given that secondary 
cytoreduction is an acceptable practice in a limited number of platinum-resistant OC 
patients in whom gross total cytoreduction can be achieved without high risk of major 
perioperative morbidity, it is reasonable to include patients with non-bulky (≤5 cm) 
disease, as well as patients with bulky disease for whom gross total cytoreduction is 
deemed achievable. Therefore, we will compare efficacy of MV-NIS therapy with 
conventional chemotherapy chosen from the above four regimens by the treating 
investigator. To ensure similar patient characteristics among patients treated with MV-
NIS versus conventional chemotherapy, we will randomize patients adjudged to be 
candidates for intraperitoneal port placement (and cytoreductive surgery, for those 
patients with >5 cm disease) to either MV-NIS or “dealer’s choice” chemotherapy, in a 
2:1 ratio, stratifying patients by the number of prior therapies to which the patient is 
resistant, as well as by disease extent (non-bulky versus bulky). In this way, we will 
compare the safety, tolerability, and clinical efficacy of MV-NIS and chemotherapy. We 
will also compare anti-tumor immune responses elicited by MV-NIS therapy with those 
elicited by chemotherapy. 
 
 

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2.0 
Goals 
2.1 
Primary objective:  
2.11 
Compare clinical efficacy of Arm A (MV-NIS therapy) and Arm B (standard 
cytotoxic chemotherapy), as measured by overall survival (OS). 
 
2.2 
Secondary clinical objectives: 
2.21 
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.  
 
2.22 
Assess safety and tolerability of MV-NIS, and compare with standard 
chemotherapy. 
 
2.23 
Compare quality of life as assessed by FACT-O between MV-NIS and standard 
chemotherapy. 
 
2.3 
Translational objectives: 
2.31 
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 SPECT/CT imaging within the NV-NIS treatment arm. 
 
2.32 
Assess viremia, viral replication, and viral shedding/persistence following 
intraperitoneal administration within the NV-NIS treatment arm. 
 
2.33 
Measure humoral and cellular immune responses to MV-NIS within the NV-NIS 
treatment arm. 
 
2.34 
Measure changes in anti-OC immune responses in both treatment arms. 
 
2.35 
Perform transcriptomic analysis on tumor biopsy specimens to determine a gene 
expression profile predictive of therapeutic response to MV-NIS. 
 
 
 

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3.0 
Patient Eligibility 
3.1 
Pre-Registration -Inclusion Criteria 
3.11 
Ability to understand and the willingness to sign a written informed consent 
document. 
3.12 
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(see Section 3.22). 
3.13  
Willingness to be evaluated for surgical placement of an intraperitoneal port and 
undergo biopsy if feasible for a research sample. 
3.2 
Registration/Randomization - Inclusion Criteria 
3.21 
Age ≥18 years. 
3.22 
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. 
3.23 
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 CA-125 ≥2 x 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 PET/CT evidence of cancer recurrence within 180 days of last dose of 
carboplatin- or cisplatin-containing chemotherapy. 
3.24 
The following laboratory values obtained ≤7 days prior to registration: 
• 
ANC ≥1500/µL 
• 
PLT ≥100,000/µL 
• 
Total bilirubin ≤ ULN 
• 
AST ≤2 x ULN  
• 
Creatinine ≤1.5 x ULN 
• 
Hgb ≥9.0 g/dL 
3.25 
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. 
3.26 
Life expectancy ≥12 weeks. 
3.27 
Willingness to provide all biologic specimens as required by the protocol. 

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3.28 
Measurable disease by RECIST criteria (see Section 11.0), 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.) 
3.29a 
Normal cardiac function, as determined by LVEF ≥ institutional lower limit of 
normal on echocardiogram or MUGA ≤1 month prior to registration. 
3.29b If DOXIL is selected as the investigator’s choice chemotherapy: 
• 
Lifetime exposure to doxorubicin ≤240 mg/m2 (or equivalent biologic dose if 
prior exposure to a different anthracycline). 
3.29c 
Candidate for surgical placement of an intraperitoneal port, as determined by a 
gynecologic oncology surgeon. 
3.29d Must have anti-measles immunity as demonstrated by serum IgG anti-measles 
antibody levels of ≥1.1 EU/ml as determined by BioPlex Measles IgG multiplex 
flow immunoassay 
3.3 
Registration/Randomization - Exclusion criteria 
3.31 
Epithelial tumors of low malignant potential, stromal tumors, and germ cell 
tumors of the ovary. 
3.32 
Evidence of measurable disease (per 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. 
3.33 
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 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. 
3.34 
Resistant to all of the following: DOXIL, GEM, TOPA, and weekly 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.)) 
3.35 
ECOG performance status (PS) of 3 or 4. 
3.36 
History of other malignancy ≤5 years prior to registration except for non-
melanoma skin cancer, carcinoma in situ of the cervix, and DCIS. 

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3.37 
Active infection ≤7 days prior to study entry. 
3.38 
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 
3.39a 
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.) 
3.39b 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 
SVT). 
3.39c 
Other cardiac or pulmonary disease that, at the investigator’s discretion, can 
impair treatment safety. 
3.39d CNS metastases or seizure disorder. 
3.39e 
HIV-positive test result, or history of other immunodeficiency. 
3.39f 
History of organ transplantation. 
3.39g History of chronic hepatitis B or C. 
3.39h Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary 
therapy considered investigational (utilized for a non-FDA-approved indication 
and in the context of a research investigation). 
3.39i 
Any concurrent medications which could interfere with the trial. 
3.39j 
History of tuberculosis or history of PPD positivity. 
3.39k 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. 
3.39l 
Exposure to household contacts ≤15 months old or household contact with 
known immunodeficiency. 
3.39m Allergy to measles vaccine or history of severe reaction to prior measles 
vaccination. 
3.39n Allergy to iodine. (NOTE: This does not include reactions to intravenous contrast 
materials.) 
3.39o Any other pathology or condition which the principal investigator may deem to 
negatively impact treatment safety. 
3.39p On anticoagulation and unable to discontinue temporarily for  up to 7 days. 

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4.0 
Test Schedule 
4.1 
Arm A: MV-NIS 
Tests and procedures 
Pre-treatment phase 
Treatment phase 
 
≤28 
days 
prior to 
regis-
tration 
≤7 days 
prior to 
regis-
tration 
Surgery  
(after  
randomization 
prior to  
Cycle 1,  
Day 1) 
After 
randomization 
after port 
placement, 
prior to  
Cycle 1, Day 1 
Cycle 1, 
Day 3 
(±1 day) 
Cycle 1, 
Day 8  
(±1 day) 
Cycle 1, 
Day 15  
(±1 day) 
≤5 days 
prior to  
Day 1 of 
Cycle 2 and 
every cycle 
thereafter 
≤5 days prior 
to Day 1 of 
Cycle 3 and 
every other 
cycle 
thereafter 
End 
of 
treat-
ment 
History, exam, vital signs, PS, weight 
 
 
 
X9 
 
 
 
X 
 
 
Assessment of AEs 
X 
 
 
X9 
 
 
 
X 
 
 
Surgical evaluation1 
X 
 
 
 
 
 
 
 
 
 
Intraperitoneal port placement and excisional 
biopsy (+ cytoreduction in patients with 
bulky disease) 
 
 
X10 
 
 
 
 
 
 
 
Hematology group2: Hb, WBC, ANC, ALC, Plt 
 
X 
 
 
 
 
 
X 
 
 
Chemistry group3: Cr, AST, AP, Tbili 
 
X 
 
X9 
 
 
 
X 
 
 
Coagulation panel4: PT, apTT, INR 
X 
 
 
 
 
 
 
 
 
 
Anti-Measles IgG testingR 
X 
 
 
 
 
 
 
 
 
 
Chest X-ray 
X 
 
 
 
 
 
 
 
 
 
Tumor imaging CT abdomen/pelvis or PET/CT 
abdomen/pelvis or MRI abdomen/pelvis 
 
 
 
X5,9 
 
 
 
 
X5 
 
CA-125 
X 
 
 
X9 
 
 
 
X 
 
 
Echocardiogram/MUGAR 
X 
 
 
 
 
 
 
 
 
 
HIV blood testR 
X 
 
 
 
 
 
 
 
 
 
Mouth gargle specimen7,R 
 
 
 
X9 
X 
X 
 
X11 
 
 
Peritoneal aspirate7,R 
 
 
X 
 
X 
X 
 
 
 
 
Urine sample7,R 
 
 
 
X9 
X 
X 
 
X11 
 
 
Research blood tests7,R 
X 
 
 
X9 
X 
X 
X 
X 
 
X 
SPECT/CT imaging8,R 
 
 
 
X9 
X 
X 
X8 
X8 
 
 
FACT-O questionnaire6 
 
 
 
X9 
 
 
 
X 
 
 
1. Pre-registration procedure: To determine if peritoneal port placement is feasible. 
[FOOTNOTES CONTINUE ON NEXT PAGE] 

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2. Hb = hemoglobin, WBC = white blood cell count, ANC = absolute neutrophil count, ALC = absolute lymphocyte count, Plt = platelet count 
3. Cr = creatinine, AST = aspartate aminotransferase, AP = alkaline phosphatase, Tbili = total bilirubin 
4. PT = prothrombin time (including international normalized ratio—INR), aPTT = activated partial thromboplastin time 
5. Measurement of indicator lesions. For surveillance during treatment, patients will undergo CT or PET/CT or MRI before every odd cycle (prior to Cycle 3, 
Cycle 5, etc) until PD. If a patient develops asymptomatic PD and wishes to continue study treatment, another CT or PET/CT or MRI will be performed after 
one additional cycle. If no further progression is noted, CT or PET/CT or MRI will be performed every other cycle. 
6. QOL booklets must be used. 
7. For a complete list of research tests, see Section 14. NOTE: Some testing is only done in Rochester. 
8. SPECT/CT scans on Cycle 1, Days 15 and 28 will be elective, based on whether there is continued uptake on prior imaging studies. SPECT/CT will only be 
performed in Cycle 2 if positive imaging is obtained in Cycle 1. In this case, SPECT/CT imaging in Cycle 2 will be timed to correspond to the most positive 
SPECT/CT in Cycle 1. 
9. These evaluations should take place after peritoneal Port placement and ≤7 days prior to initiation of MV treatment (≤14 days for CT/MRI). 
10. To be completed per treatment Section 7.11; 4 weeks (±2 week) prior to administration of Cytomel®. A biopsy should be attempted in all patients, if tissue 
is not found, patient remains eligible. For patients with bulky disease, cytoreduction to no gross residual disease should be attempted; however, if this is not 
feasible, the patient is still eligible for IP port placement and protocol treatment. 
11. Prior to Cycle 2 only. 
R. Research-funded 
 
4.2 
Arm B: Cytotoxic chemotherapy (non-bulky disease ≤5 cm) 
Tests and procedures 
Pre-treatment phase 
Treatment phase 
 
≤28 days 
prior to 
regis-
tration 
≤7 days 
prior to 
regis-
tration 
After 
randomization, 
prior to  
Cycle 1, Day 19 
Day 8 of 
each cycle  
(±3 days) 
Day 15 of 
each cycle 
(±3 days) 
≤7 days prior 
to Day 1 of 
Cycle 2 and 
every cycle 
thereafter12 
≤7 days prior to 
Day 1 of Cycle 3 
and every other 
cycle thereafter12 
End of 
treatment 
History, exam, vital signs, PS, weight 
 
 
X 
 
 
 
X 
 
Assessment of AEs 
X 
 
X 
 
 
 
X 
 
Surgical evaluation1 
X 
 
 
 
 
 
 
 
Hematology group2: Hb, WBC, ANC, ALC, Plt 
 
X 
X 
X8 
X8 
X 
 
 
Chemistry group3: Cr, AST, AP, Tbili 
 
X 
X 
 
 
X 
 
 
Coagulation panel4: PT, apTT, INR 
X 
 
 
 
 
 
 
 
Anti-Measles IgG testingR 
X 
 
 
 
 
 
 
 
Chest X-ray 
X 
 
 
 
 
 
 
 
CT abdomen/pelvis or PET/CT abdomen/pelvis 
or MRI abdomen/pelvis5 
 
 
X 
 
 
 
X5 
 
CA-12511 
X 
 
X 
 
 
X 
 
 
Echocardiogram/MUGA 
XR 
 
 
 
 
 
X6 
 

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Tests and procedures 
Pre-treatment phase 
Treatment phase 
 
≤28 days 
prior to 
regis-
tration 
≤7 days 
prior to 
regis-
tration 
After 
randomization, 
prior to  
Cycle 1, Day 19 
Day 8 of 
each cycle  
(±3 days) 
Day 15 of 
each cycle 
(±3 days) 
≤7 days prior 
to Day 1 of 
Cycle 2 and 
every cycle 
thereafter12 
≤7 days prior to 
Day 1 of Cycle 3 
and every other 
cycle thereafter12 
End of 
treatment 
HIV blood testR 
X 
 
 
 
 
 
 
 
Research blood tests7,R 
X 
 
X 
 
 
X10 
X10 
X 
FACT-O questionnaire13 
 
 
X 
 
 
 
X 
 
1. Pre-registration procedure: To determine if peritoneal port placement is feasible. 
2. Hb = hemoglobin, WBC = white blood cell count, ANC = absolute neutrophil count, ALC = absolute lymphocyte count, Plt = platelet count 
3. Cr = creatinine, AST = aspartate aminotransferase, AP = alkaline phosphatase, Tbili = total bilirubin 
4. PT = prothrombin time (including international normalized ratio—INR), aPTT = activated partial thromboplastin time 
5. Measurement of indicator lesions. For surveillance during treatment, patients will undergo CT or PET/CT or MRI before every odd cycle (Cycle 3, Cycle 5, 
etc) until PD. If a patient develops asymptomatic PD and wishes to continue study treatment, another CT or PET/CT or MRI will be performed after one 
additional cycle. If no further progression is noted, CT or PET/CT, or MRI will be performed every other cycle. 
6. For patients receiving DOXIL, an echocardiogram or MUGA is required once the patient has received 480 mg/m2 DOXIL or equivalent and every other 
cycle thereafter while receiving DOXIL therapy. 
7. For a complete list of research tests, see Section 14. NOTE: No research tests are required for Arm B patients in Florida and Arizona. 
8. Day 8 and Day 15 Hematology group testing is required only for patients receiving GEM, TAXOL, or TOPA. 
9. ≤7 days prior to initiation of treatment. 
10. ONLY for patients receiving chemotherapy at Mayo Clinic in Rochester, MN. Prior to Cycle 2, Day 1; After Cycle 2, research blood tests will be performed 
at the same times as the patient undergoes CT or PET/CT or MRI abdomen pelvis (i.e., before every odd cycle starting with Cycle 3). 
11. Not required at non-Mayo visits, but if obtained, CA-125 results are to be submitted even if the test is completed more often. 
12. Data may be submitted more often if there are clinic visits where tests and procedures are conducted. 
13. QOL booklets must be used. They are completed prior to each cycle of treatment. If an Arm B patient will be receiving treatment without a monthly clinic 
visit, send extra booklets and stamped return envelopes home with the patient so the patient may complete the questionnaires at the appropriate times and 
return them to the clinic. 
R 
Research-funded 
 
 
 

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4.3 
Arm B: Cytotoxic chemotherapy (bulky disease >5 cm) 
Tests and procedures 
Pre-treatment phase 
Treatment phase 
 
≤28 days 
prior to 
regis-
tration 
≤7 days 
prior to 
regis-
tration 
Surgery (after 
randomization  
prior to Cycle 1,  
Day 1) 
After randomization,  
after port placement, 
prior to Cycle 1,  
Day 19 
Day 8 
of each 
cycle 
(±3 
days) 
Day 15 
of each 
cycle 
(±3 
days) 
≤7 days prior to 
Day 1 of 
Cycle 2 and 
every cycle 
thereafter12 
≤7 days prior to 
Day 1 of Cycle 3 
and every other 
cycle thereafter12 
End of 
treatment 
History, exam, vital signs, PS, weight 
 
 
 
X 
 
 
 
X 
 
Assessment of AEs 
X 
 
 
X 
 
 
 
X 
 
Surgical evaluation1 
X 
 
 
 
 
 
 
 
 
Cytoreductive surgery and excisional 
biopsy 
 
 
X10 
 
 
 
 
 
 
Hematology group2: Hb, WBC, ANC, 
ALC, Plt 
 
X 
 
 
X11 
X11 
X 
 
 
Chemistry group3: Cr, AST, AP, Tbili 
 
X 
 
X 
 
 
X 
 
 
Coagulation panel4: PT, apTT, INR 
X 
 
 
 
 
 
 
 
 
Anti-Measles IgG testingR 
X 
 
 
 
 
 
 
 
 
Chest X-ray 
X 
 
 
 
 
 
 
 
 
CT abdomen/pelvis or PET/CT 
abdomen/pelvis or MRI 
abdomen/pelvis 
 
 
 
X5 
 
 
 
X5 
 
CA-125 
X 
 
 
X 
 
 
X 
 
 
Echocardiogram/MUGAR 
X 
 
 
 
 
 
 
X8 
 
HIV blood testR 
X 
 
 
 
 
 
 
 
 
Research blood tests7,R 
X 
 
 
X 
 
 
X14 
X14 
X 
FACT-O questionnaire6 
 
 
 
X 
 
 
X 
 
 
1. Pre-registration procedure: To determine if peritoneal port placement is feasible. 
2. Hb = hemoglobin, WBC = white blood cell count, ANC = absolute neutrophil count, ALC = absolute lymphocyte count, Plt = platelet count 
3. Cr = creatinine, AST = aspartate aminotransferase, AP = alkaline phosphatase, Tbili = total bilirubin 
4. PT = prothrombin time (including international normalized ratio—INR), aPTT = activated partial thromboplastin time 
5. Measurement of indicator lesions. For surveillance during treatment, patients will undergo CT or PET/CT or MRI before every odd cycle (prior to Cycle 3, 
Cycle 5, etc) until PD. If a patient develops asymptomatic PD and wishes to continue study treatment, another CT or PET/CT or MRI will be performed after 
one additional cycle. If no further progression is noted, CT or PET/CT or MRI will be performed every other cycle. 
6. QOL booklets must be used. They are completed prior to each cycle of treatment. If an Arm B patient will be receiving treatment without a monthly clinic 
visit, send extra booklets and stamped return envelopes home with the patient so the patient may complete the questionnaires at the appropriate times and 
return them to the clinic. 

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7. For a complete list of research tests, see Section 14. NOTE: No research tests are required for Arm B patients in Florida and Arizona. 
8. For patients receiving DOXIL, an echocardiogram or MUGA is required once the patient has received 480 mg/m2 DOXIL or equivalent and every other cycle 
thereafter while receiving DOXIL therapy. 
9. ≤7 days prior to initiation of treatment. 
10. To be completed per treatment Section 7.11; 4 weeks (±2 week) prior to Cycle 1, Day 1. Cytoreduction and biopsy should be attempted in all patients, if 
tissue is not found or removed, patient remains eligible. 
11. Day 8 and Day 15 Hematology group testing is required only for patients receiving GEM, TAXOL, or TOPA. 
12. Not required at non-Mayo visits, but if obtained, CA-125 results are to be submitted even if the test is completed more often. 
13. Data may be submitted more often if there are clinic visits where tests and procedures are conducted. 
14. ONLY for patients receiving chemotherapy at Mayo Clinic in Rochester, MN: Prior to Cycle 2, Day 1; After Cycle 2, research blood tests will be performed 
at the same times as the patient undergoes CT or PET/CT or MRI abdomen pelvis (i.e., before every odd cycle starting with Cycle 3). 
R. Research-funded 
 

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5.0 
Stratification Factors 
5.1 
Number of control arm regimens to which the patient is resistant (see definition of 
resistance under Section 3.34): 0 vs. 1 vs. 2 vs. 3. 
5.2 
ECOG performance status: 0 vs. 1vs. 2. 
5.3 
Extent of disease at enrollment: ≤2 cm vs. greater than 2 cm but less than or equal to 
5 cm vs. >5 cm. 
6.0 
Registration/Randomization Procedures 
6.1 
Pre-Registration (Step 1)  
6.11 
To register a patient, access the Mayo Clinic Cancer Center (MCCC) web page 
and enter the registration/randomization application. The registration/ 
randomization application is available 24 hours a day, 7 days a week. Back up 
and/or system support contact information is available on the website. If unable 
to access the website, call the MCCC Registration Office at 
 
between the hours of 8 a.m. and 5:00 p.m. Central Time (Monday through 
Friday). 
The instructions for the registration/randomization application are available on 
the MCCC web page 
and detail the 
process for completing and confirming patient registration. Prior to initiation of 
protocol treatment, this process must be completed in its entirety and an MCCC 
subject ID number must be available as noted in the instructions. It is the 
responsibility of the individual and institution registering the patient to confirm 
the process has been successfully completed prior to release of the study agent. 
Patient registration via the registration/randomization application can be 
confirmed in any of the following ways: 
• 
Contact the MCCC Registration Office 
If the patient 
was fully registered, the MCCC Registration Office staff can access 
the information from the centralized database and confirm the 
registration. 
• 
Refer to “Instructions for Remote Registration” in section 
“Finding/Displaying Information about A Registered Subject.” 
6.12 
Prior to accepting the pre-registration, the registration/randomization application 
will verify the following: 
• 
IRB approval at the registering institution 
• 
Patient pre-registration eligibility  
• 
Existence of a signed consent form   
• 
Existence of a signed authorization for use and disclosure of protected health 
information. 
6.13 
Pre-registration tests/procedures (see Section 4.0) must be completed within the 
guidelines specified on the test schedule. 
6.2 
Registration Requirement:  
NOTE: Patient case must be evaluated by a gynecologic oncologist prior to registration. 
6.21 
To register a patient, access the Mayo Clinic Cancer Center (MCCC) web page 
and enter the registration/randomization application.  The registration/ 
randomization application is available 24 hours a day, 7 days a week. Back up 
and/or system support contact information is available on the website. If unable 

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to access the website, call the MCCC Registration Office at 
 
between the hours of 8 a.m. and 4:30 p.m. Central Time (Monday through 
Friday). 
The instructions for the registration/randomization application are available on 
the MCCC web page 
and detail the 
process for completing and confirming patient registration. Prior to initiation of 
protocol treatment, this process must be completed in its entirety and an MCCC 
subject ID number must be available as noted in the instructions. It is the 
responsibility of the individual registering the patient to confirm the process has 
been successfully completed prior to release of the study agent. Patient 
registration via the registration/randomization application can be confirmed in 
any of the following ways: 
• 
Contact the MCCC Registration Office 
If the patient 
was fully registered, the MCCC Registration Office staff can access the 
information from the centralized database and confirm the registration. 
• 
Refer to “Instructions for Remote Registration” in section 
“Finding/Displaying Information about A Registered Subject.” 
6.22 
A mandatory correlative research component is part of this study, the patient will 
be automatically registered onto this component (see Sections 3.27, 14.1 and 
17.1). 
6.23 
Documentation of IRB approval must be on file in the Registration Office before 
an investigator may register any patients. 
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file (no less than annually) at the Registration Office 
 If the necessary documentation is not submitted in advance 
of attempting patient registration, the registration will not be accepted and the 
patient may not be enrolled in the protocol until the situation is resolved. 
When the study has been permanently closed to patient enrollment, submission of 
annual IRB approvals to the Registration Office is no longer necessary. 
6.24 
At the time of registration, Registration Randomization Application will verify 
the following: 
• 
IRB approval 
• 
patient eligibility  
6.25 
At the time of registration, the following will be recorded: 
• 
Patient has/has not given permission to store and use his/her 
sample(s) for future research at Mayo. 
• 
Patient has/has not given permission to store and use his/her 
sample(s) for future research to learn, prevent, or treat other health 
problems. 
• 
Patient has/has not given permission for MCCC to give his/her 
sample(s) to researchers at other institutions. 
6.26 
Consent and treatment on this protocol must commence at Mayo Clinic 
Rochester or a participating site under the supervision of a gynecologic 
oncologist. 
6.27 
Treatment cannot begin prior to registration. For patients in Arm A, surgery must 
occur ≤14 days after registration. For patients in Arm B, chemotherapy must 

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begin ≤14 days after registration in non-Bulky Disease patients, 14-42 days after 
surgery in Bulky Disease patients. 
6.28 
Pretreatment tests/procedures (see Section 4.0) must be completed within the 
guidelines specified on the test schedule. 
6.29a 
All required baseline symptoms (see Section 10.5) must be documented and 
graded. 
6.29b Blood draw kits will be available on site for patients being treated at Mayo Clinic 
and will be given or sent to patients being treated at local institutions (Arm B 
only), as needed. 
6.29c 
Patient questionnaire booklets must be utilized; copies are not acceptable for this 
submission. 
6.3 
Randomization Procedures 
6.31 
The factors defined in Section 5.0, together with the registering membership, will 
be used as stratification factors. 
6.32 
After the patient has been registered into the study, the values of the stratification 
factors will be recorded, and the patient will be assigned in a 2:1 fashion to one 
of the following treatment groups using the Pocock-Simon dynamic allocation 
procedure which assigns patients to the arm that minimizes the stratification 
factor imbalance with 75% probability (28). The procedure has been shown to be 
able to accommodate a large number of factors (10-20) without difficulty (29). 
We use the range method and the stratification factors are all assumed to have 
equal weights. 
• 
Arm A: MV-NIS  
• 
Arm B: Cytotoxic Chemotherapy  
6.33 
For patients with bulky disease (>5 cm), the study coordinator will assure the 
surgeon is aware of the arm assignment AFTER debulking so the surgeon knows 
whether to place the intraperitoneal port or whether to proceed with surgical 
closure. See Appendix V. 
 
 

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7.0 
Protocol Treatment 
There are different surgical procedures post-registration depending on bulky vs non-bulky 
disease, thus patients with bulky disease will be unblinded post biopsy and debulking. Upon 
surgeon notification of arm assignment, those on Arm A will undergo port placement prior to 
surgical closure (see Section 7.122) and those on Arm B will undergo surgical closure (see 
Section 7.222). 
7.1 
Treatment schedule – Arm A (MV-NIS) 
7.11 
Pre-Registration 
7.111 Patients with non-bulky disease will be evaluated for intraperitoneal port 
placement by a gynecologic oncologist. 
7.112 Patients with bulky disease will be evaluated for cytoreductive surgery 
and intraperitoneal port placement by a gynecologic oncologist. If 
deemed a candidate for surgery, a second gynecologic oncologist must 
review imaging studies and concur that surgery is appropriate. 
7.12 
Post-Registration 
7.121 Patients with non-bulky disease will have surgery for biopsy and 
intraperitoneal port placement. A waiting period of 4 weeks (±2 weeks) 
will commence prior to receipt of Cytomel®. 
7.122 Patients with bulky disease will undergo surgery for biopsy and 
debulking. Patients will undergo intraperitoneal port placement prior to 
surgical closure. A waiting period of 4 weeks (±2 weeks) will commence 
prior to receipt of Cytomel®. 
Pre-medication Prior to Administration of MV-NIS 
Agent 
Dose 
Route 
Day 
Cytomel®* 
0.025 mg 1 tablet three times a day 
Day -7 through day of last 
SPECT/CT scan 
*For a patient who is receiving thyroid replacement (e.g., levothyroxine), discuss the 
case with Endocrinology prior to administering Cytomel®. It may be appropriate to 
reduce or omit Cytomel® for patients receiving thyroid replacement to avoid 
thyrotoxicosis. 
 
MV-NIS Administration 
Agent 
Dose 
Route 
Day 
Re RX 
MV-NIS 
109 TCID50 
IP 
1 
q 4 wks 
After MV-NIS Administration 
123I 
5 mCi (±10%) 
Oral 
Day 3 and 8 of study  
(2 additional doses may be 
given for imaging based on 
imaging results) 
 
 
7.123 Patients will receive Cytomel® to prevent thyroid uptake when 
repeated imaging doses of 123I are administered. 

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7.124 The in vivo distribution of MV-NIS infected cells and the kinetics of virus 
spread and elimination will be monitored by SPECT/CT imaging of the 
abdomen and pelvis after oral 123I administration (2 hours after a range of 
–5 mCi, ±10%). 
SPECT/CT imaging (i.e. abdomen and pelvis) will be performed on Days3 
and 8 after MV-NIS administration. In addition patients may be imaged 
on Days 15 and 28. These scans will be elective, based on whether there 
is continued uptake on prior imaging studies. Imaging by SPECT/CT is 
to be performed in Cycle 2 only if positive imaging is obtained in Cycle 
1. In this case, SPECT/CT imaging in Cycle 2 will be timed to 
correspond to SPECT/CT in Cycle 1. 
7.125 The virus will be administered through intraperitoneal port that will be 
surgically placed at the time of study entry. If ascites is present, it will be 
drained through the intraperitoneal port prior to administration of MV- 
NIS. The patient will receive an infusion of the assigned dose of MV-
NIS diluted in 500 ml of NS over 30 minutes. Treatment will be 
administered at the Clinical Research and Trials Unit (CRTU). 
7.126 In Rochester, patients will be admitted the evening prior to 
administration and dismissed 24 hours after administration of the agent.  
For the first cycle, patients should be observed for at least 8 hours after 
administration. Patients who are not local will need to stay in town 
overnight to ensure no subacute issues arise.  
For subsequent cycles, the agent will be administered in the outpatient 
setting and the patients will be observed in the facility for at least one 
hour and up to three hours after administration of the agent.  
A saline lock for IV access, if necessary, will be placed prior to viral 
administration. 
7.2 
Treatment schedule – Arm B 
7.21 
Pre-Registration 
7.211  Patients with non-bulky disease will be evaluated for intraperitoneal port 
placement by a gynecologic oncologist. 
7.112 Patients with bulky disease will be evaluated for cytoreductive surgery 
and intraperitoneal port placement by a gynecologic oncologist.  If 
deemed a candidate for surgery, a second gynecologic oncologist must 
review imaging studies and concur that surgery is appropriate. 
7.22 
Post-Registration 
7.221 Patients with non-bulky disease will not be subject to a waiting period 
and may start treatment within 7 days post-registration/randomization but 
no later than 14 days. 
7.222 Patients with bulky disease will undergo surgery for biopsy and 
debulking. After completion of debulking, patients will NOT undergo 
intraperitoneal port placement and will simply have surgical closure. A 
waiting period of 4 weeks (±2 weeks) will commence prior to receipt of 
chemotherapy. 
7.223 Treatment is with one of the following agents: liposomal doxorubicin, 
gemcitabine, topotecan, or paclitaxel, as selected by the treating 

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investigator. Premedications may be adjusted after Cycle 1, Day 1 at the 
discretion of the treating investigator. The treating investigator may 
select any of the four treatment options to which a patient is not already 
resistant based on clinical judgment or based on chemotherapy 
sensitivity assays, including participation in a clinical trial using tumor 
xenografts to predict chemotherapy sensitivity. 
7.224 A patient may not begin study on one treatment and switch to a different 
treatment. If the clinician determined the selected treatment is not 
beneficial to the patient, the patient will go off treatment for the purposes 
of this study and will be followed per protocol (see Section 13.61). 
7.23 
Information per Treatment Agent 
7.231 
Liposomal Doxorubicin 
7.2311 
Pretreatment 
Agent 
Dose 
Route 
Day 
Dexamethasone* 
10-20 mg 
PO (preferred) or IV 
1 
*Dexamethasone is optional at the discretion of the treating investigator.  Default 
is to omit. 
7.2312 
Protocol treatment 
Agent 
Dose 
Route 
Day 
Retreatment 
Liposomal Doxorubicin 
(DOXIL) 
40 mg/m2 IV* 
1 
Every 28 days. 
*In 250 ml D5W over one hour.  Initial rate is 1 mg/min and increased after the 
first 30 minutes of uneventful observation to be completed over 1 hour. 
7.232 
Gemcitabine 
7.2321 
Pretreatment 
Agent 
Dose 
Route 
Day 
Dexamethasone* 
Per institutional 
standard of care 
PO (preferred) 
or IV 
1, 8, 15 
*Dexamethasone is optional at the discretion of the treating investigator. Default 
is to omit. 
7.2322 
Protocol treatment 
Agent 
Dose 
Route 
Day 
Retreatment 
Gemcitabine 
(GEM) 
1000 mg/m2 
IV* 
1, 8, 15 
Every 28 days. 
*Round to nearest 100 mg. Give in 250 mL 0.9 Normal Saline IV infusion over 
30 minutes. 
 
 

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Amendment 8 
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7.233 
Topotecan 
7.2331 
Pretreatment 
Agent 
Dose 
Route 
Day 
Dexamethasone* 
Per institutional 
standard of care 
PO (preferred) 
or IV 
1, 8, 15 
*Dexamethasone is optional at the discretion of the treating investigator. Default 
is to omit. 
7.2332 
Protocol treatment 
Agent 
Dose 
Route 
Day 
Retreatment 
Topotecan (TOPA) 
4 mg/m2 
IV* 
1, 8, 15 
Every 28 days. 
*In 100 ml D5W or 0.9 Normal Saline IV infusion over 30 minutes. 
7.234 
Paclitaxel 
7.2341 
Pretreatment 
Agent 
Dose 
Route 
Day 
Dexamethasone 
20 mg 
IV* 
1 
Dexamethasone 
10 mg 
IV* 
8, 15 
Famotidine 
20 mg 
IV* 
1, 8, 15 
Diphenhydramine 
50 mg 
IV* 
1 
Diphenhydramine 
25 mg 
IV* 
8, 15 
*Give 15 minutes before paclitaxel. 
7.2342 
Protocol treatment 
Agent 
Dose 
Route Day 
Retreatment 
Paclitaxel (TAXOL) 
80 mg/m2 IV* 
1, 8, 15 
Every 28 days. 
*In 250 ml 0.9% Normal Saline IV infusion over 1 hour. 
7.235 
Bevacizumab 
Bevacizumab may be added to liposomal doxorubicin, topotecan, or 
paclitaxel, NOT gemcitabine 
7.2351 
Pretretment - None 
7.2352 
Protocol treatment 
Agent 
Dose 
Route Day 
Retreatment 
Bevacizumab (BEV) 
10 mg/kg 
IV 
1, 15 
Every 28 days. 

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8.0 
Dosage Modification Based on Adverse Events 
For Arm A, strictly follow the modifications in this table until individual treatment tolerance can 
be ascertained. For Arm B (all FDA-approved therapies), the dose modifications are suggestions, 
and actual dose modification will be performed at the discretion of the treating provider. (The 
treating provider does not need to be from the consenting site for patients randomized to Arm B.) 
If multiple adverse events are seen, administer dose based on greatest reduction required for any 
single adverse event observed. Dose modifications apply to the treatment given in the preceding 
cycle and are based on adverse events observed since the prior dose. 
8.1 
Criteria for dose delays, dose modifications, and treatment discontinuation 
ALERT: ADR reporting may be required for some adverse events. See Section 10.0 
 Use Common Terminology Criteria for Adverse Events (CTCAE) v4.0 unless otherwise specified  
CTCAE 
CATEGORY 
ADVERSE EVENT 
AGENT(S) 
DOSE MODIFICATIONS 
BASED ON INTERVAL ADVERSE EVENT (Day 8 or Day 15) 
Investigations 
Platelet count 
decreased Grade 2+: 
<75,000 
GEM, 
TOPA, or 
TAXOL  
Omit treatment until ≤Grade 1, then ↓ by one dose 
level. If no recovery to ≤Grade 1 after 21 days, then 
discontinue treatment and follow up per Section 18. 
Neutrophil count 
decreased Grade 3+: 
<1,000 
All other non-
hematologic 
categories* 
Nonhematologic 
Grade 3 
Omit treatment until ≤Grade 1, then ↓ by one dose 
level. If no recovery to ≤Grade 1 after 14 days, then 
discontinue treatment and follow up per Section 18. 
Grade 4 
Discontinue treatment and follow up per Section 18. 
AT SCHEDULED RETREATMENT (e.g. Day 1 of subsequent cycle) 
Investigations 
Platelet count 
decreased  
75,000-100,000 
DOXIL, 
GEM, 
TOPA, 
TAXOL, or  
MV-NIS 
Hold treatment until ≤Grade 1 and platelet count 
>100,000. If this is the first treatment delay for a 
patient at this dose level, then it is acceptable to 
continue this dose level or ↓ by one dose level (at the 
discretion of the treating investigator). If this the 
second treatment delay, then ↓ by one dose level. If 
no recovery to ≤Grade 1 after 14 days, then 
discontinue treatment and follow up per Section 18. 
Neutrophil count 
decreased  
Grade 2: 1,000-1,500 
Platelet count 
decreased  
Grade 2+: <75,000 
Hold treatment until ≤Grade 1, then ↓ by one dose 
level. If no recovery to ≤Grade 1 after 14 days, then 
discontinue treatment and follow up per Section 18. 
Neutrophil count 
decreased  
Grade 3+: <1,000 
All other non-
hematologic 
categories* 
Nonhematologic 
Grade 3 
Hold treatment until ≤Grade 1, then ↓ by one dose 
level. If no recovery to ≤Grade 1 after 14 days, then 
discontinue treatment and follow up per Section 18. 
Grade 4 
Discontinue treatment and follow up per Section 18 

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CTCAE 
CATEGORY 
ADVERSE EVENT 
AGENT(S) 
DOSE MODIFICATIONS 
Viremia 
Any 
MV-NIS 
Hold treatment until viral titer undetectable and 
recheck weekly, then ↓ by one dose level. If no 
recovery to undetectable after 14 days, then 
discontinue treatment and follow up per Section 18. 
*Dose modification for nausea and vomiting will be implemented only if they persist despite 
optimal antiemetic treatment. 
 
8.2 
Dose levels 
Agent 
Initial treatment 
(dose level 0) 
First dose reduction 
(dose level -1) 
Second dose reduction 
(dose level -2) 
Third dose reduction 
(dose level -3) 
DOXIL* 
40 mg/m2 
30 mg/m2 
20 mg/m2 
Discontinue treatment 
GEM* 
1000 mg/m2 
750 mg/m2 
500 mg/m2 
Discontinue treatment 
TOPA* 
4 mg/m2 
3 mg/m2 
2 mg/m2 
Discontinue treatment 
TAXOL* 
80 mg/m2 
60 mg/m2 
40 mg/m2 
Discontinue treatment 
MV-NIS 
109 TCID50 
108 TCID50 
107 TCID50 
Discontinue treatment 
*For Arm B patients, the above dose levels are suggestions. Dose modifications will be initiated by 
the treating provider. 
 
9.0 
Ancillary Treatment 
9.1 
Full Supportive Care 
Patients should receive full supportive care while on this study. This includes blood 
product support, antibiotic treatment and treatment of other newly diagnosed or 
concurrent medical conditions. All blood products and concomitant medications such as 
antidiarrheals, analgesics, anti-emetics received from the first administration of study 
drugs until 30 days after the final dose are to be recorded in the medical record. 
9.2 
Antiemetics and Antidiarrheals 
Prophylactic administration of antiemetics or antidiarrheals prior to Cycle 1 Day 1 of 
treatment will not be allowedfor patients on Arm A. However, antiemetics and/or 
antidiarrheals may be given prior to all other treatments should a patient develop 
nausea/vomiting/diarrhea associated with treatment. 
Acceptable treatment options for nausea/vomiting include: 
• 
ondansetron 4-8 mg po q 8 hours prn or 4 mg IV q 8 hours prn 
• 
granisetron 1 mg po q 12 hours prn or 10 mcg/kg q 12 hours prn 
• 
prochlorperazine 5-10 mg po q 6-8 hours prn, 25 mg rectally bid prn, or 2.5-5 mg IV 
by slow infusion (5 mg/min) q 6 hours prn 
• 
lorazepam 0.5-2 mg po q 4-6 hours prn 
• 
Dexamethasone as an antiemetic is not allowed for patients on Arm A. 
Acceptable treatment options for diarrhea include:  
Loperamide 4 mg after first diarrheal bowel movement and 2 mg after each subsequent 
one up to 16 mg a day and atropine sulfate/diphenoxylate hydrochloride (Lomotil) 2 tab q 
6 hours prn or 10 ml q 6 hours prn. 

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Acceptable treatment options for fever include acetaminophen 500 mg 1-2 tabs q 4-6 
hours prn up to 4 grs a day and NSAIDs, such as ibuprofen 400 mg q 4-6 hours prn or 
naproxen 250-500 mg bid. 
9.3 
Bevacizumab infusion reactions 
If a patient develops an infusion reaction to bevacizumab, the patient may be treated with 
acetaminophen 650 mg by mouth every 4 hours as needed for fever, diphenhydramine 
25 mg by mouth every 4 hours as needed for infusion reactions (may repeat after 
15 minutes if first dose ineffective), and meperidine 25 mg IV every 15 minutes as 
needed for rigors (maximum dose 50 mg). 
9.4 
Measles - diagnosis 
Diagnosis of measles in this trial is based on the CDC definition of clinical measles and 
includes: 
• 
a generalized rash lasting ≥3 days, and 
• 
temperature ≥38.3°C (≥101°F), and 
• 
cough, coryza, and conjunctivitis. 
 
9.5 
Measles - treatment 
Should a patient develop measles, treatment with immune globulin will be administered 
400 mg/kg/d for 3-5 days. Aerosolized ribavirin (6 gr/d) can also be considered at the 
discretion of the treating physician for patients not responding to immune globulin. 
Patients who develop measles will be removed from the trial and followed up to 15 years 
for evidence of persistent toxicity. 
 
9.6 
Co-enrollment in other trials 
Patients randomized to Arm A are not to be considered for enrollment in any other study 
involving a pharmacologic agent (drugs, biologics, immunotherapy approaches, gene 
therapy) during enrollment on MC1365, whether for symptom control or therapeutic 
intent. Patients randomized to Arm B may be considered for concurrent enrollment in 
other studies of pharmacologic agents for symptom control, but not in studies of 
pharmacologic agents for therapeutic intent. 
 
9.7 
Echocardiogram/MUGA for DOXIL Treatment 
Patients receiving DOXIL must undergo an echocardiogram or MUGA upon reaching a 
lifetime doxorubicin dose of 480 mg/m2 (or equivalent amount when added with other 
anthracyclines), and every other cycle thereafter. Left ventricular ejection fraction 
(LVEF) must be within normal limits to continue DOXIL. 
 
 
 

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10.0 
Adverse Event (AE) Reporting and Monitoring 
10.1 
Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
4.0 will be utilized for AE reporting. All appropriate treatment areas should have access 
to a copy of the CTCAE version 4.0. A copy of the CTCAE version 4.0 can be 
downloaded from the CTEP web site: 
 
10.11 Adverse event monitoring and reporting is a routine part of every clinical trial. 
First, identify and grade the severity of the event using the CTCAE version 4.0. 
Next, determine whether the event is expected or unexpected (refer to Section 
10.2) and if the adverse event is related to the medical treatment or procedure 
(see Section 10.5). With this information, determine whether an adverse event 
should be reported as an expedited report (see Section 10). Expedited reports are 
to be completed within the timeframes and via the mechanisms specified in 
Sections 10.4. All AEs reported via expedited mechanisms must also be reported 
via the routine data reporting mechanisms defined by the protocol (see Sections 
10.5 and 18.0). 
10.12 
Each CTCAE term in the current version is a unique representation of a specific event 
used for medical documentation and scientific analysis and is a single MedDRA 
Lowest Level Term (LLT). Grade is an essential element of the Guidelines and, in 
general, relates to severity for the purposes of regulatory reporting to NCI. 
NOTE: A severe AE, as defined by the above grading scale, is NOT the same 
as serious AE which is defined in the table in Section 10.4 
10.2 
Expected vs. Unexpected Events  
• 
The determination of whether an AE is expected is based on agent-specific 
information provided in Section 15.0 of the protocol and the study specific 
consent form. 
• 
Unexpected AEs are those not listed in the agent-specific information 
provided in Section 15.0 of the protocol and the study specific consent form. 
NOTE: “Unexpected adverse experiences” means any adverse experience that is not 
identified in nature, severity, or frequency of risk in the information provided for 
IRB review nor mentioned in the consent form.  
10.3 
Assessment of Attribution 
When assessing whether an adverse event is related to a medical treatment or procedure, 
the following attribution categories are utilized. 
Definite - The adverse event is clearly related to the agent(s). 
Probable - The adverse event is likely related to the agent(s). 
Possible - The adverse event may be related to the agent(s). 
Unlikely - The adverse event is doubtfully related to the agent(s). 
Unrelated - The adverse event is clearly NOT related to the agent(s). 
Events determined to be possibly, probably or definitely attributed to a 
medical treatment suggest there is evidence to indicate a causal relationship 
between the drug and the adverse event. 
 
 

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10.4 
Expedited Reporting Requirements for IND/IDE Agents  
Phase 1 and Early Phase 2 Studies: Expedited Reporting Requirements for Adverse Events that 
Occur on Studies under an IND/IDE within 30 Days of the Last Administration of the 
Investigational Agent/Intervention 1, 2 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor ANY Serious Adverse Events, whether or not they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or subject 
and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. (FDA, 
21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the sponsor within 
the timeframes detailed in the table below.  
Hospitalization 
Grade 1 and Grade 2 Timeframes 
Grade 3-5 
Timeframes 
Resulting in 
Hospitalization  
≥24 hrs 
7 Calendar Days 
24-Hour 3 Calendar 
Days 
Not resulting in 
Hospitalization 
≥24 hrs 
Not required 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” - The AE must initially be reported within 24 hours of learning of the AE, 
followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” - A complete expedited report on the AE must be submitted within 7 calendar days of 
learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• All Grade 3, 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• Grade 2 AEs resulting in hospitalization or prolongation of hospitalization 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered.  Footnote “1” above 
applies after this reporting period. 
Effective Date: May 5, 2011 
Additional instructions: 
1. Use Mayo Clinic Cancer Center Electronic Serious Adverse Event Reporting Form 
 
2. Provide copies to 
by email  
3. The MCCC Regulatory Affairs Unit (RAU) Risk Information Specialist who will determine 
and complete IRB reporting. The RAU will submit to the MCCC SAE Coordinator and the 
MCCC IND Coordinator to determine if FDA submission is needed. 

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10.5 
Required Routine Reporting  
Adverse events to be graded at each evaluation and pretreatment symptoms/conditions to 
be evaluated at baseline per the CTCAE v4.0 grading unless otherwise stated in the table 
below: 
Category 
Adverse events/Symptoms 
Baseline 
Each evaluation 
General Disorders and 
Administrative Site 
Conditions 
Fever  
X 
X 
Chills 
X 
X 
Skin and subcutaneous 
tissue disorders 
Rash maculo-papular 
X 
X 
Palmar-plantar 
erythrocysesthesia syndrome 
X 
X 
Gastrointestinal disorders 
Diarrhea  
 
X 
# of stools 
X 
 
Flatulence 
X 
X 
Nausea 
X 
X 
Vomiting 
X 
X 
Enterocolitis infectious 
X 
X 
Respiratory, thoracic and 
mediastinal disorders 
Dyspnea  
X 
X 
Neurologic disorders 
Peripheral sensory 
neuropathy 
X 
X 
Peripheral motor neuropathy 
X 
X 
Cardiovascular disorders 
Left ventricular systolic 
dysfunction 
X 
(once the patient reaches a 
lifetime cumulative dose of 
DOXIL of 480 mg/m2, then 
every other cycle thereafter) 
10.51 Submit via appropriate MCCC Case Report Forms (i.e., paper or electronic, as 
applicable) the following AEs experienced by a patient and not specified in 
Section 10.5: 
10.511 Grade 2 AEs deemed possibly, probably, or definitely related to the study 
treatment or procedure. 
10.512 Grade 3 and 4 AEs regardless of attribution to the study treatment or 
procedure. 
10.513 Grade 5 AEs (Deaths) 
10.5131 
Any death within 30 days of the patient’s last study 
treatment or procedure regardless of attribution to the study 
treatment or procedure. 
10.5132 
Any death more than 30 days after the patient’s last study 
treatment or procedure that is felt to be at least possibly 
treatment related must also be submitted as a Grade 5 AE, 
with a CTCAE type and attribution assigned. 
 

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11.0 
Treatment Evaluation 
For the purposes of this study, patients should be re-evaluated every 8 weeks. Modified Response 
Evaluation Criteria in Solid Tumors (RECIST) criteria will be used. 
11.1 
Definitions 
11.11 Measurable disease: the presence of at least one measurable lesion.  
11.12 Measurable lesions: lesions that can be accurately measured in at least one 
dimension with longest diameter >20 mm.  With spiral CT scan, lesion must be  
>10 mm in at least one dimension. 
11.13 Non-measurable lesions: all other lesions, including small lesions (longest 
diameter <20 mm with conventional techniques or <10 mm with spiral CT) and 
other non-measurable lesions. These include: ascites; abdominal masses that are 
not confirmed and followed by imaging techniques; and cystic lesions. 
11.2 
Response Criteria 
11.21 Evaluation of target lesions 
A maximum of 4 (two per organ) measurable lesions should be identified as 
target lesions and recorded and measured at baseline.  Target lesions should be 
selected on the basis of their size (lesions with the longest diameter) and their 
suitability for accurate repetitive measurements (either by imaging techniques or 
clinically). A sum of the longest diameter (LD) for all target lesions will be 
calculated and reported as the baseline sum LD. The baseline sum LD will be 
used as reference to further characterize the objective tumor response of the 
measurable dimension of the disease. 
Complete Response (CR): Disappearance of all target lesions and normalization 
of CA125 if elevated at baseline. 
Partial Response (PR): 
At least 30% decrease in the sum of the longest 
diameter (LD) of target lesion taking as reference the 
baseline sum LD 
Progression (PD): 
As least a 20% increase in the sum of LD of target 
lesions taking as reference the smallest sum LD 
recorded since the treatment started or the 
appearance of one or more new lesions 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD taking as 
references the smallest sum LD 
11.22 Evaluation of non-target lesions 
All other lesions (or sites of disease) should be identified as non-target lesions 
and should also be recorded at baseline. Measurements are not required, and 
these lesions should be followed as “present” or “absent.” 
Complete Response (CR): Disappearance of all non-target lesions and 
normalization of tumor maker level 
Non-Complete 
Response: (non-CR): 
Persistence of one or more non-target lesions or/and 
maintenance of tumor marker level above the normal 
limits 

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Progression (PD): 
Appearance of one or more new lesions.  
Unequivocal progression of existing non-target 
lesions. Although a clear progression of “non-target” 
lesions only is exceptional, in such circumstances, 
the opinion of the treating physician should prevail, 
and the progression status should be confirmed at a 
later time by the review panel (or study chair). 
Notes: 
• 
If tumor markers are measured and are initially above the upper normal limit, 
they must normalize for a patient to be considered in complete clinical 
response. 
• 
Cytology and histology 
If the measurable disease is restricted to a solitary lesion, its neoplastic nature 
should be confirmed by cytology/histology. 
These techniques can be used to differentiate between PR and CR in rare 
cases (for example, residual lesions in tumor types such as germ cell tumors, 
where known residual benign tumors can remain). 
The cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment when the measurable tumor has met 
criteria for response or stable disease is mandatory to differentiate between 
response or stable disease (an effusion may be a side effect of the treatment) 
and progressive disease. 
11.23 Evaluation of response by CA-125 
11.231 
CA-125 should not be used in evaluating response to therapy unless 
there is no measurable or evaluable disease by imaging criteria as 
defined above. 
11.232 
If a patient has no measurable or evaluable disease by imaging criteria, 
responses are defined as follows: 
Complete Response (CR): 
Normalization of CA-125 
Partial Response (PR): 
At least 50% decrease in CA-125 
Progression (PD): 
As least a 50% increase in CA-125 
Stable Disease (SD): 
Neither sufficient decrease in CA-
125 to qualify for PR nor sufficient 
increase to qualify for PD 
11.24 Evaluation of best overall response 
The best overall response is the best response recorded from the start of the 
treatment until disease progression/recurrence (taking as reference for 
progressive disease the smallest measurements recorded since the treatment 
started). The patient’s best response assignment will depend on the achievement 
of both measurement and confirmation criteria. 
 
 

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Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Notes: 
Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as 
“symptomatic deterioration.”  Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
In some circumstances, it may be difficult to distinguish residual disease from normal 
tissue.  When the evaluation of complete response depends upon this determination, it is 
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) before 
confirming the complete response status. 
11.3 
Guidelines for Evaluation of Measurable Disease 
All measurements should be recorded in metric notation using a ruler or calipers.  All 
baseline evaluations should be performed as close as possible to the treatment start and 
never more than 4 weeks before the beginning of the treatment. 
Note: Tumor lesions in a previously irradiated area are not optimally considered 
measurable disease. 
The same method of assessment and the same technique should be used to characterize 
each identified and reported lesion at baseline and during follow-up.  Imaging-based 
evaluation is preferred to evaluation by clinical examination when both methods have 
been used to assess the antitumor effect of a treatment. 
• 
Conventional CT and MRI should be performed with cuts of 10mm or less in slice 
thickness contiguously.  Spiral CT should be performed using a 5 mm contiguous 
reconstruction algorithm.  This applies to the chest, abdomen, and pelvis.  
11.4 
Duration of response 
11.41 Duration of overall response 
The duration of overall response is measured from the time measurement criteria 
are met for CR/PR (whichever is first recorded) until the first date that recurrent 
or progressive disease is objectively documented (taking as reference for 
progressive disease the smallest measurements recorded since the treatment 
started). 
The duration of overall complete response is measured from the time 
measurement criteria are first met for CR until the first date that recurrent disease 
is objectively documented. 
 
 

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11.42 Duration of stable disease 
Stable disease is measured from the start of the treatment until the criteria for 
progression are met, taking as reference the smallest measurements recorded 
since the treatment started.  
 
12.0 
Descriptive factors 
12.1 
Serous histology: Yes vs. No. 
12.2 
Prior bevacizumab: Yes vs. No. 
12.3 
Measurable disease: Yes vs. No. 
 
13.0 
Treatment/ Follow-up Decision at Evaluation of Patient 
13.1 
Patients will be treated until PD. 
13.2 
Patients who have not had PD at time of their reassessment and have not experienced 
intolerable toxicity will be allowed to continue protocol treatment at the same dose level 
until PD. 
13.3 
Those patients who have not had PD but have experienced unacceptable toxicity may be 
eligible for retreatment at a lower dose (see Section 8.0). 
13.4 
Patients with PD but no progression of cancer-related symptoms may continue study 
treatment (either Arm) for one additional cycle at the discretion of the treating 
investigator followed by restaging studies. If the new imaging and/or CA-125 do not 
demonstrate additional PD, then patients may continue protocol treatment and will revert 
to the disease evaluation plan detailed in Section 4.0. (The imaging and/or CA-125 that 
initially demonstrated PD will serve as a new baseline going forward.) If the new 
imaging and/or CA-125 demonstrate additional PD, then patients will go off treatment 
and will be followed as described in Section 18.1. 
13.5 
Those patients who have had PD with progression of cancer-related symptoms will go off 
treatment and will be followed as described in Section 18.1. 
13.6 
Off-Study Criteria 
13.61 Those patients who refuse further treatment, or are on Arm B and will be 
changing treatment regimens, will go off treatment and will be followed for the 
purpose of this study as described in Section 18.1. 
13.62 A screen failure is a consented subject that has not been registered/randomized 
and fails to satisfy eligibility criteria or has decided not to continue treatment 
(either on their own behalf or under the direction of their physician). 
• 
All materials required for pre-randomization and a Screen Failure CRF will 
be submitted. 
13.63 A patient is deemed ineligible if after registration, it is determined that at the time 
of registration, the patient did not satisfy each and every eligibility criteria for 
study entry. The patient may continue treatment off-protocol at the discretion of 
the physician as long as there are no safety concerns, and the patient was 
properly registered. The patient will go directly to the event-monitoring phase of 
the study (or off study, if applicable). 

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• 
If the patient received treatment, all data up until the point of confirmation of 
ineligibility must be submitted.  Event monitoring will be required per 
Section 18.0 of the protocol.  
• 
If the patient never received treatment, on-study material must be submitted. 
Event monitoring will be required per Section 18.0 of the protocol. 
 
13.64 A patient is deemed a major violation, if protocol requirements regarding 
treatment in cycle 1 of the initial therapy are severely violated that evaluability 
for primary end point is questionable. All data up until the point of confirmation 
of a major violation must be submitted. The patient will go directly to the event-
monitoring phase of the study. The patient may continue treatment off-protocol at 
the discretion of the physician as long as there are no safety concerns, and the 
patient was properly registered. Event monitoring will be required per section 
18.0 of the protocol. 
 
13.65 A patient is deemed a cancel if he/she is removed from the study for any reason 
before any study treatment is given. On-study material and the End of Active 
Treatment/Cancel Notification Form must be submitted. The patient will go 
directly to the event-monitoring phase of the study, and event monitoring will be 
required per Section 18.0 of the protocol. 
 

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14.0 
Pharmacologic/Correlative Studies 
14.1 
Summary Table of Research Blood and Body Fluid Specimens to be Collected for this Protocol 
14.11 Arm A: MV-NIS 
Assessment 
Mandatory 
or optional 
Blood or 
body fluid 
being 
collected 
Volume 
to collect 
per tube 
Prior to 
registration 
≤7 days prior to 
Cycle 1, Day 1 
Cycle 1, 
Days 3 and 
8 
Cycle 1, 
Day 15 
≤5 days prior 
to Day 1 each 
subsequent 
cycle 
End of 
treatment 
Storage 
Immunologic1 Mandatory 
Blood 
Variable 
5 mL  
(1x5 mL red top 
tube) 
20 mL  
(2x10 mL red top 
tubes) 
 
 
5 mL  
(1x5 mL red 
top tube) 
5 mL  
(1x5 mL red 
top tube) 
Ambient 
Immunologic1 Mandatory 
Blood 
Variable 
60 mL  
(6x10 mL green 
top tubes or 1x60 
mL heparin 
syringe) 
180 mL  
(18x10 mL green 
top tubes or 3x60 
mL heparin 
syringes)  
10 mL  
(1 x 10 mL 
green top 
tube)  
10 mL  
(1 x 10 mL 
green top 
tube)  
60 mL  
(6x10 mL 
green top 
tubes or 1x60 
mL heparin 
syringe)  
60 mL  
(6x10 mL 
green top 
tubes or 1x60 
mL heparin 
syringe)  
Ambient 
Viral 
Mandatory 
Blood 
5 mL 
 
5 mL 
(2 x 2.5mL 
PAXgene tubes) 
5 mL 
(2 x 2.5mL 
PAXgene 
tubes) 
5 mL 
(2 x 2.5mL 
PAXgene 
tubes) 
5 mL 
(2 x 2.5mL 
PAXgene 
tubes)4 
5 mL 
(2 x 2.5mL 
PAXgene 
tubes) 
Ambient 
Viral1 
Mandatory 
Urine 
50 mL 
 
X 
X 
 
X4 
 
Frozen -80°C 
after processing 
and adding 
Trizol at CRTU 
Viral1 
Mandatory 
Mouth 
gargle 
50 mL 
 
X 
X 
 
X4 
 
Frozen -80°C 
after processing 
and adding 
Trizol at CRTU 
Viral1 
Mandatory Peritoneal 
fluid2 
500 mL 
 
X3 
X 
 
 
 
On ice after 
draw 
1. Rochester only: This testing will *only* be done for patients seen in Rochester MN. 
2. Before administering MV-NIS, attempt to aspirate 500 ml of peritoneal fluid. If less than 100 ml of fluid can be aspirated, add 1000 ml of 
0.9 normal saline intraperitoneally and re-attempt to aspirate up to 500 ml of peritoneal fluid. NOTE: If aspiration was attempted and no 
aspirate was obtained, it is not a deviation. 
3. Use peritoneal fluid obtained at the time of port placement for this instance (≤7 days prior to Cycle 1, Day 1) only. 
4. Prior to Cycle 2 only.  
 

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14.12 Arm B: Cytotoxic Chemotherapy – Rochester only 
Assessment 
Mandatory 
or optional 
Blood or 
body fluid 
being 
collected 
Volume to 
collect per 
tube 
Prior to 
registration 
≤7 days prior 
to Cycle 1 
Prior to Cycle 2 
(Only for Pts 
treated at Mayo 
Clinic) 
≤7 days prior to 
Day 1 of Cycle 3 
and every other 
cycle thereafter2 
End of 
treatment 
Storage 
Immunologic1 
Mandatory 
Blood 
Variable 
5 mL  
(1x5 mL red top 
tube) 
20 mL  
(2x10 mL red 
top tubes) 
5 mL  
(1x5 mL red top 
tube) 
5 mL  
(1x5 mL red top 
tube) 
5 mL  
(1x5 mL red 
top tube) 
Ambient 
Immunologic1 
Mandatory 
Blood 
Variable 
60 mL  
(6x10 mL green 
top tubes or 
1x60 mL 
heparin syringe) 
180 mL  
(18x10 mL 
green top tubes 
or 3x60 mL 
heparin 
syringes) 
60 mL  
(6x10 mL green 
top tubes or 
1x60 mL heparin 
syringe) 
60 mL  
(6x10 mL green 
top tubes or 1x60 
mL heparin 
syringe) 
60 mL  
(6x10 mL 
green top tubes 
or 1x60 mL 
heparin 
syringe) 
Ambient 
1. Rochester only: This testing will *only* be done for patients seen in Rochester, MN. 
2. After Cycle 2, research blood tests will be performed at the same times as the patient undergoes imaging for their cancer (i.e., before every 
odd cycle starting with Cycle 3) 
14.2 
Shipping and Handling 
14.21 Samples collected in CRTU (Rochester) will be processed and held perTables 14.11and 14.12 until picked up by  
 
 
 
 
 
 
 
 
14.22 Samples collected at Mayo Clinic in Florida or Arizona will be shipped overnight: 
• 
PAXgene blood tubes – room temperature overnight shipping 
 
 
 
 
 

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14.3 
Background and Methodology  
(Protocols for assays conducted by Mayo Clinic Department of Laboratory Medicine not 
included). 
The goals of the immunologic studies is to determine whether an immune measurement 
or tissue marker can predict increased clinical benefit from MV-NIS treatment relative to 
cytotoxic chemotherapy, and to determine how MV-NIS impacts the endogenous 
immune response to OC. 
 
14.31 Interferon gamma (IFN-γ) ELISpot Assay 
ELISpot Assays measure the frequency of responding antigen-specific T cells per 
unit of peripheral blood mononuclear cells (PBMCs). On Day 1, 2.5 x105 
PBMCs/well will be plated into 96-well plates in 3-well replicates in 200 mcl of 
RPMI-1640 containing 10% human AB serum (T-cell medium) in the presence 
or absence of 10 mcg/ml peptide antigen. The cells will be incubated at 37°C. For 
the 10 day assay, IL-2 (Zeptometric, Inc. Buffalo, NY) will be added to 10 U/ml 
on day 5. On Day 8, 2.5 x 105/well irradiated autologous PBMCs and 10 mcg/ml 
antigens (folate receptor alpha—FRα, HER-2, IGFBP2, p53, NY-ESO-1, 
mesothelin, and MV) will be added. On day 9, the cells are then transferred to an 
anti-IFN-γ−coated nitrocellulose (NC)-plate (Millipore Corporation, Bedford, 
MA). The NC-plate will be incubated (37°C) for a further 20–24 hours followed 
by washing three times using PBS containing 0.05% Tween-20. Alternatively, 
for the 3 day assay, antigens will be added on day 1. For both assays, once 
incubation with antigen is complete, the plate will be incubated for 2.5 hours at 
RT in PBS with 5 mcg/ml biotinylated anti–IFN-γ Ab, washed in PBS, and 
further incubated with 100 mcl/well avidin-horseradish peroxidase (HRP, Vector 
Laboratories, Burlingame, CA)) for 2 hours at room temperature. The anti-IFN-γ 
and biotinylated anti-IFN-γ antibody pair will be obtained from Mabtech 
(Sweden). After 3 washes in PBS, the plate will be incubated with 100 mcl/well 
HRP-colorimetric substrate (BD Biosciences) for 20 minutes, rinsed with cool 
tap water, and allowed to dry completely. The nitrocellulose plates will be read 
on an AID ELISpot reader (Cell Technology, Inc., Columbia MD, reader 
software v.3.1.1.). A positive response is defined as a frequency that is 
significantly (p<0.05, two-tailed t test) greater than the mean of control no-
antigen wells and detectable (i.e., >1:100,000). We will test responses to media 
(negative control), phorbol 12-myristate 13-acetate (PMA) and ionomycin 
(positive control), Candida, Influenza vaccine, folate receptor alpha (FRα), and 
insulin-like growth factor receptor binding protein two (IGFBP2). 
 
14.32 Multiplexed Cytokine Analysis  
Antigen-specific cytokine profiles will also be examined to determine the 
skewing of the T cell response. PBMCs (4 x 105) will be cultured in 200 mcl 
medium (RPMI 1640 medium plus 10% FBS plus 1% penicillin/streptomycin/ 
glutamine) containing the immune stimulus of interest (or media alone) in 
duplicate wells of a microtiter plate. The PBMCs will be incubated at 37°C in 5% 
CO2 for 48 h; the supernatants subsequently harvested, transferred to a storage 
plate, and frozen at –80°C for later analysis. A panel of 17 cytokines and 
chemokines will be analyzed using a multiplexed approach with commercially 
available human 17-plex kits. The following cytokines will be assessed: IL-1β, 
IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12, IL-13, IL-17A, IFN-γ, 

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TNF-α, CCL2 (MCP-1), CCL4 (MIP-1β), G-CSF, and GM-CSF. A customized 
platform obtained from Meso Scale Discovery (Gaithersburg, MD) will be used 
to determine the cytokine concentrations using the Sector 2400 instrument (Meso 
Scale Discovery). Cytokine concentrations will be determined based on a 
standard curve generated on each plate using the manufacturer-supplied reagents.  
 
14.33 Enzyme-linked immunosorbent assay (ELISA) 
Antibodies are a key aspect of immune responses to tumors. Antigen 
(10 mcg/well) will be prepared in 0.06 M carbonate buffer and added to ELISA 
microtiter plates for 24 hours. Antigens will include media (negative control), 
Candida, Influenza vaccine, FRα, IGFBP2, tetanus, keyhole limpet hemocyanin 
(KLH), and p53. Antigens to be tested include Plates will be washed with PBS 
and blocked with 3% BSA-PBS. One hundred microliters of diluted sera (1:100 
for peptide and 1:40 for tetanus toxoid in 1%BSA-PBS) will be added and the 
plates further incubated for 24 hr followed by washing with PBS/0.1% Tween-
20. A 1:2000 dilution of anti-IgG-HRP is then added to wells for 1 hour followed 
by washing and color development after adding 100 mcl TMB (3,3’,5,5’ 
tetramethylbenzidine) substrate to the wells. Color development is stopped with 
50 mcl of a 0.1N HCl solution. For the standard curve, serial dilutions of human 
IgG will be added to separate wells. Optical densities will be read on a Softmax 
Pro multiplate reader. A treatment-induced increase in OC antigen-specific 
antibody responses will be defined as (1) a 2-fold or greater increase in OC 
antigen-specific antibody at any point during treatment if there were detectable 
pre-treatment levels of OC antigen-specific T cells or (2) OC antigen-specific 
antibodies at any point during treatment if pre-treatment levels of OC antigen-
specific antibodies are non-detectable. 
 
14.34 Detection and quantitation of MV nucleoprotein mRNA from blood, urine, and 
mouth gargle specimens 
Assessment of viremia and viral shedding.  
Patient’s peripheral blood mononuclear cells will be monitored for evidence of 
measles virus viremia. This will be performed by collecting 2.5 ml of blood in 
PAXgene Blood RNA tubes (2 tubes per each time point draw) according to the 
manufacturer’s recommendations (Qiagen). The PAXgene Blood RNA tube, is 
part of a system used to collect blood for RNA extraction ona proprietary reagent 
that immediately stabilizes intracellular RNA for three days at room temperature 
(18 to 25C) and five days when kept in a regular fridge (2 to 8C).  
Viral shedding will be assessed by quantitative RT-PCR of throat gargle 
specimens(s) and urine samples, both being processed under sterile conditions at 
CRU. Testing will be performed 
  
Sample processing in CRTU for viremia and viral shedding will be done using 
sterile techniques and laminar flow hood. Mouth wash (gargle) samples consist 
of 2 x 15 ml of commercial Scope® mouth rinsing fluid (or equivalent) that are 
gargled in the back of the throat (not swished in the mouth) and then are 
collected in 50 ml sterile conical tubes (a total of 15 ml needs to returned for 
further processing), spun down at 3000rpm and the supernatant discarded. The 
remaining pellet is suspended in 1 ml Trizol® reagent (Invitrogen Cat 
#15596026-100ml, or Cat# 10296028-200ml), mixed well and transferred to 

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sterile 2 ml cryovials. The samples are kept in a negative 80 freezer until picked 
up by 
will be notified 
to pick up the samples. 
Urine will be collected by clean catch method in a container set up by nursing, 
then transferred to sterile 50ml tubes (a maximum of eight tubes will be 
processed for each time point). The tubes are spun down at 3000 rpm, the 
supernatant discarded and 1 ml Trizol reagent added to each pellet, mixed well 
and each pellet transferred to a 2 ml cryovial. The samples processed will be kept 
in a negative 80 freezer. 
will be notified to pick up the 
samples. 
Quantitative RT-PCR will be performed as previously described (24). Briefly, the 
quantitative RT-PCR assay was optimized for primers, probe, and magnesium 
concentration with TaqMan RNA to CT 1-step kit.. A 50-μL quantitative RT-
PCR reaction volume will be used to amplify  the  MV-N genomic RNA target, 
in the presence of 0.3 mmol/L each of forward (5′-GGG TGT GCC GGT TGG 
A-3’) and reverse (5′-AGA AGC CAG GGA GAG CTA CAG A-3’)  -primers, 
0.2 mmol/L Black Hole Quencher–labeled probe (5′-/56-FAM/TGG GCA GCT 
CTC GCA TCA CTT GC/ 3BHQ_1/-3′), 4 mmol/L MgCl, and 1 mcg or a 
maximum total volume of 5 mcl of the RNA isolate. One cycle of reverse 
transcriptase reaction (15 min at 48°C) will be applied, followed by a 
denaturation step (10 min at 95°C) and 40 cycles of amplification (15 s 95°C and 
1 min 60°C), with fluorescence measured during the extension. A standard curve 
of 10-fold dilutions containing 107 to 10 MV-N gene copies/mL will be 
generated using a manufactured RNA oligo (IDT) () and having the following 
sequence: 5′-rGrGrG rUrGrU rGrCrC rGrGrU rUrGrG rArArG rArUrG rGrGrU 
rArGrC rUrCrU rCrGrC rArUrC rArCrU rUrGrC rUrCrU rGrCrU rGrGrG 
rCrCrC rGrGrU rUrUrC rUrCrU rGrUrA rGrCrU rCrUrC rCrCrU rGrGrC 
rGrGrC rUrUrC rU-3′-3′. Quantification and subsequent calculation of copy 
number will be done using the standard curve and the ROCHE480 Quantitative 
PCR System software. 
14.35 Isolation of cells from peritoneal aspirates and detection of viral replication by 
Vero cell overlay assay. 
After peritoneal fluid is received in the laboratory, cells will be separated from 
the supernatant by centrifugation. Subsequently, the different cell populations 
will be separated using a Percoll gradient as previously described (25). The 
identity of epithelial ovarian carcinoma cells will be confirmed by 
immunostaining for cytokeratin E1/E3(26, 27). Vero cells will be (American 
Type Culture Collection) plated at a concentration of 2 × 105 per well and 
incubated overnight at 37°C. The next day, 103 patient cells isolated from the 
peritoneal fluid will be added to duplicate wells. SKOV.IP3 or SKOV3 cells 
infected with MV-NIS at a multiplicity of infection of 1.0, and MV-NIS will be 
used as positive controls. Plates will be incubated for 5 d and will be examined 
daily for syncytia formation. 
14.36 Transcriptomic analysis of peripheral blood immune cell subsets 
Participating patients will be asked to give at least 1, preferably 2 samples of 
blood - no less than 1 day apart and no more than 4 weeks apart – both draws to 
be prior to receiving the first dose of treatment. 
 

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Peripheral blood (up to 40 ml) will be drawn into heparinized tubes. Procedures 
will be put into place to ensure immediate pick-up of blood samples: a special 
studies card will be printed to direct person drawing blood to page the research 
lab prior to drawing the blood. Lab personnel will retrieve the samples from the 
blood draw area and hand-carry to the research laboratory in Guggenheim. 
Samples will be coded and de-identified once they are received in the lab. Blood 
will be processed immediately: immune cell subsets will be isolated, select 
subsets will be stimulated ex vivo, and RNA will be purified from these cell 
subsets. ONLY the final RNA preparations will be stored prior to batch analysis 
(library construction and sequencing). Library construction, NextGen RNA 
sequencing, and Bioinformatics processing will be conducted by the Mayo 
Genomics Facility. 
 
 
 

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15.0 
Drug Information 
15.1 
MV-NIS (NIS-Measles Virus – Edmonston Strain) 
MV-NIS is a live, tissue culture adapted measles virus engineered to express the human 
thyroidal sodium iodide symporter (NIS). The virus was constructed by inserting the NIS 
gene (cDNA) into a full-length infectious molecular clone of an attenuated Edmonston 
lineage measles virus (MV-tag). This virus is not a vaccine. MV-NIS propagates on Vero 
cells with kinetics equivalent to the parental strain of virus. It propagates selectively in 
human cancer cells that it infects by binding preferentially to CD46, a membrane protein 
that is overexpressed in tumor cell lines including myeloma. The virus is directly 
cytopathic to tumor cells leading to the formation of multinucleated syncytia that die by 
apoptosis. MV-NIS infected tumor cells express NIS, a membrane ion channel that 
actively transports iodide into cells. Radioiodine uptake by cells expressing NIS provides 
the basis for in vivo radioiodine imaging that can reveal the profile of MV-NIS gene 
expression and the location of MV-NIS infected cells during virus spread and 
elimination.  
 
15.11 Preparation and storage: MV-NIS will be prepared at the Virus and Vector 
Production Laboratory (VVPL) of the Molecular Medicine Program at Mayo 
Clinic and stored at -80°C. The virus will be thawed and mixed with normal 
saline prior to administration. (See Appendix IV) 
 
15.12 Administration: MV-NIS will be administered intraperitoneally (30 minutes) in 
500 ml of normal saline under close observation in the Clinical Research Unit.  
 
15.13 Known potential adverse events: 
15.131 The most common adverse effect noted is burning and stinging at the site 
of injection; however, this is not applicable in this study given 
intraperitoneal administration. Occasionally, moderate fever 38.3°-
39.4°C has been noted in the month after vaccination, usually within 5-
12 days after injection. Rash, which is usually minimal, has been noted. 
Less commonly, high fever over 39.4°C or mild lymphadenopathy have 
been reported.  
15.132 Occasional reactions: 
• 
Moderate to high fever lasting 1-2 days, starting within a week or 
two of the vaccination 
• 
A rash, lasting 1-2 days 
• 
Cough and rhinitis 
• 
Erythema multiforme (skin rash) 
15.133 Unexpected and rare reactions associated with measles vaccines: 
• 
Allergic reactions to the vaccine including anaphylaxis  
• 
Reactions at the injection site such as wheal, flare or urticaria 
• 
Thrombocytopenia 
• 
Diarrhea 
 
15.14 Nursing guidelines: Due to the very early investigational nature of this drug, no 
nursing guidelines are known. Please monitor patients closely and follow Section 
10.0. More than 90% of the U. S. population has measles virus immunity as a 

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result of natural infection or immunization. Immune status for measles virus is 
mandatory for Mayo Medical Center personnel. Therefore administration of the 
agent is not expected to result in any risk for nursing or ancillary staff. 
 
15.2 
Doxorubicin Liposomal (Doxil®) 
15.21 Background: Doxorubicin Liposomal inhibits DNA and RNA synthesis by 
intercalating between DNA base pairs causing steric obstruction and inhibits 
topoisomerase-II at the point of DNA cleavage. Doxorubicin Liposomal is also a 
powerful iron chelator. The iron-doxorubicin complex can bind DNA and cell 
membranes, producing fee hydroxyl (OH) radicals that cleave DNA and cell 
membranes. Doxorubicin is active throughout entire cell cycle. Doxorubicin 
Liposomal is a pegylated formulation which protects the liposomes, and thereby 
increases blood circulation time. 
15.22 Formulation: Commercially available for injection, solution: 2 mg/mL (10 mL, 
30 mL) 
15.23 Preparation, storage, and stability: Store intact vials of solution under 
refrigeration at 2ºC to 8ºC (36ºF to 46ºF); avoid freezing. Prolonged 
freezing may adversely affect liposomal drug products, however, short-
term freezing (<1 month) does not appear to have a deleterious effect. See 
the treatment section of the protocol for specific dilution instructions. 
Generally, dose of doxorubicin liposomal less than or equal to 90 mg 
should be diluted in 250 mL of D5W prior to administration. Doses greater 
than 90 mg should be diluted in 500 mL D5W. Diluted doxorubicin 
liposomal may be refrigerated at 2ºC to 8ºC (36ºF to 46ºF); administer 
within 24 hours. Do not infuse with in-line filters. 
15.24 Administration:  Refer to the treatment section of the protocol for specific 
administration instructions. Doxorubicin Liposomal is usually administered 
IVPB over 60 minutes; manufacturer recommends administering at initial rate of 
1 mg/minute to minimize risk of infusion reactions until the absence of a reaction 
has been established, then increase the infusion rate for completion over 1 hour. 
Do not administer I.M. or SubQ. Do not infuse with in-line filters. Avoid 
extravasation (irritant), monitor site; extravasation may occur without stinging or 
burning. Flush with 5-10 mL of D5W solution before and after drug 
administration, incompatible with heparin flushes. Monitor for local 
erythematous streaking along vein and/or facial flushing (may indicate rapid 
infusion rate).  
15.25 Pharmacokinetic information: 
Distribution: Vdss: 2.7-2.8 L/m2 
Protein binding, plasma: Unknown; nonliposomal (conventional) 
doxorubicin: 70% 
Metabolism: Hepatic and in plasma to doxorubicinol and the sulfate and 
glucuronide conjugates of 4-demethyl,7-deoxyaglycones 
Half-life elimination: Terminal: Distribution: 4.7-5.2 hours, Elimination: 
44-5 hours 
Excretion: Urine (5% as doxorubicin or doxorubicinol) 
 
 

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15.26 Potential Drug Interactions:   
Cytochrome P450 Effect: Substrate (major) of CYP2D6; 3A4; Inhibits 
CYP2B6 (moderate), 2D6 (weak), 3A4 (weak) 
Increased Effect/Toxicity: Bevacizumab and trastuzumab may enhance 
the cardiotoxic effect of anthracycline antineoplastics. Cyclosporine may 
increase the levels/effects of doxorubicin; may increase neurotoxicity 
and/or enhance hematologic toxicity. Doxorubicin may potentiate the 
toxicity of cyclophosphamide (hemorrhagic cystitis) and mercaptopurine 
(hepatotoxicity). CYP2D6 inhibitors may increase the levels/effects of 
doxorubicin. CYP3A4 inhibitors may increase the levels/effects of 
doxorubicin. Sorafenib may increase the levels/effects of doxorubicin. 
Paclitaxel may reduce doxorubicin clearance and increase toxicity, 
including cardiotoxicity of doxorubicin. 
Decreased Effect: Doxorubicin Liposomal may decrease the absorption of 
cardiac glycosides. CYP3A4 inducers may decrease the levels/effects of 
doxorubicin. Doxorubicin may diminish the therapeutic effect of stavudine 
and zidovudine. 
Ethanol/Nutrition/Herb Interactions 
Ethanol: Avoid ethanol (due to GI irritation). 
Herb/Nutraceutical: St John’s wort may decrease doxorubicin levels. 
 
15.27 Known potential adverse events: Consult the package insert for the most 
current and complete information. 
U.S. Boxed Warnings: 
Doxorubicin may cause cumulative, dose-related myocardial toxicity 
(concurrent or delayed). 
Acute infusion reactions may occur, some may be serious/life-threatening. 
Use with caution in patients with hepatic impairment. 
Severe myelosuppression may occur. 
Liposomal formulations of doxorubicin should NOT be substituted for 
conventional doxorubicin hydrochloride on a mg-per-mg basis. 
Common known potential toxicities, >10%: 
Cardiovascular: Peripheral edema 
Central nervous system: Fever, headache, pain 
Dermatologic: Alopecia, palmar-plantar erythrodysesthesia/hand-foot 
syndrome, rash 
Gastrointestinal: Stomatitis, vomiting, nausea, mucositis, constipation, 
anorexia, diarrhea, dyspepsia, intestinal obstruction 
Hematologic: Myelosuppression, neutropenia, leukopenia, 
thrombocytopenia, anemia 
Neuromuscular & skeletal: Weakness, back pain 
Respiratory: Pharyngitis, dyspnea 
Miscellaneous: Infection 
Less common known potential toxicities, 1% - 10%: 
Cardiovascular: Cardiac arrest, chest pain, edema, hypotension, pallor 
tachycardia, vasodilation 
Central nervous system: Agitation, anxiety, chills, confusion, depression, 
dizziness, emotional lability, insomnia, somnolence, vertigo 

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Dermatologic: Acne, bruising, dry skin, dermatitis, furunculosis, 
maculopapular rash, pruritus, skin discoloration, vesiculobullous rash 
Endocrine & metabolic: Dehydration, hyperbilirubinemia, Hypercalcemia, 
hyperglycemia, hypokalemia, hyponatremia 
Gastrointestinal: Abdomen enlarged, anorexia, ascites, cachexia, 
dyspepsia, dysphagia, esophagitis, flatulence, gingivitis, glossitis, ileus, 
mouth ulceration, oral moniliasis, rectal bleeding, taste perversion, weight 
loss, xerostomia 
Genitourinary: Cystitis, Dysuria, leucorrhea, pelvic pain, Polyuria, urinary 
urgency, vaginal bleeding, vaginal moniliasis 
Hematologic: Hemolysis, prothrombin time increased 
Hepatic: ALT increased 
Local: Thrombophlebitis 
Neuromuscular & skeletal: Arthralgia, hypertonia, myalgia, neuralgia, 
neuritis (peripheral), neuropathy, paresthesia, pathological fracture 
Ocular: Conjunctivitis, dry eyes, retinitis 
Otic: Ear pain 
Renal: Albuminuria, hematuria 
Respiratory: Apnea, cough, epistaxis, pleural effusion, pneumonia, rhinitis, 
sinusitis 
Miscellaneous: Allergic reaction; infusion-related reactions; moniliasis, 
diaphoresis 
Rare known potential toxicities, <1% (Limited to important or life-
threatening):  
Abscess, acute brain syndrome, abnormal vision, acute myeloid leukemia 
(secondary), alkaline phosphatase increased, anaphylactic or anaphylactoid 
reaction, asthma, balanitis, blindness, bone pain, bronchitis, BUN 
increased, bundle branch block, cardiomegaly, cardiomyopathy, cellulitis, 
CHF, colitis, creatinine increased, cryptococcosis, diabetes mellitus, 
erythema multiforme, erythema nodosum, eosinophilia, fecal impaction, 
flu-like syndrome, gastritis, glucosuria, hemiplegia, hemorrhage, hepatic 
failure, hepatitis, hepatosplenomegaly, hyperkalemia, hypernatremia, 
hyperuricemia, hyperventilation, hypoglycemia, hypolipidemia, 
hypomagnesemia, hypophosphatemia, hypoproteinemia, hypothermia, 
injection site hemorrhage, injection site pain, jaundice, ketosis, lactic 
dehydrogenase increased, kidney failure, lymphadenopathy, lymphangitis, 
migraine, myositis, optic neuritis, palpitation, pancreatitis, pericardial 
effusion, petechia, pneumothorax, pulmonary embolism, radiation injury, 
sclerosing cholangitis, seizure, sepsis, skin necrosis, skin ulcer, syncope, 
tenesmus, thromboplastin decreased, thrombosis, tinnitus, urticaria, visual 
field defect, ventricular arrhythmia 
15.28 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
15.29 Nursing Guidelines:  
15.291 
Check CBC and platelet counts.  Instruct patient to watch for signs of 
infection, bleeding, and anemia. 
 

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15.292  
Advise patient that their urine may turn pink in color for approximately 
24 hours after administration of the drug. 
 
15.293 
Adriamycin is a vesicant. Check IV patency before and frequently 
during administration. If extravasation occurs, refer to institutional 
extravasation policy. 
 
15.294 
Hair loss occurs 2-4 weeks after initial injection and can be complete. 
Regrowth begins 2-3 months after discontinuation. 
 
15.295 
Beware of Adria “flare” that can occur during administration.  The 
reaction consists of an erythematous streak up the vein receiving the 
infusion.  Adjacent veins may also demonstrate red streaks.  Urticaria 
and pruritus can be associated with the reaction.  The use of 
corticosteroids and/or antihistamines has been helpful. 
 
15.296 
Administer antiemetics to minimize nausea and vomiting. 
 
15.297 
Assess for alterations in mucous membranes. Stomatitis occurs within 
7-10 days after injection.  It begins with burning sensation and can 
progress to ulceration, which can last 3 days. Carafate slurry may be 
useful.  Adequate nutritional counseling is important. Topical 
anesthetics such as viscous Xylocaine can be used symptomatically. 
 
15.298 
Advise patient that there is often significant malaise and fatigue  
1-2 weeks after injection. 
 
15.299a Adriamycin may potentiate toxicity of other antineoplastic therapies. It 
has reportedly exacerbated Cyclophosphamide (Cytoxan, CTX) 
induced hemorrhagic cystitis. 
 
15.299b  Assess heart and lung sounds. Monitor vital signs (resting pulse). Be 
alerts to early signs of cardiotoxicity, i.e., dyspnea, steady weight gain, 
nonproductive cough, arrhythmias, tachycardia, and pulmonary rales. 
Instruct patients to report any of these signs or symptoms to their health 
care provider. 
 
15.299c  Document cumulative dose, which should not exceed maximum 
cumulative dose. 
 
15.299d Advise patient of probable facial flushing for several hours after drug 
administration, especially if given quickly. 
 
 
 

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15.3 
Gemcitabine (Gemzar®) 
15.31 Background: Gemcitabine is a pyrimidine antimetabolite that inhibits DNA 
synthesis by inhibition of DNA polymerase and ribonucleotide reductase, 
specific for the S-phase of the cell cycle. Gemcitabine is phosphorylated 
intracellularly by deoxcytidine kinase to gemcitabine monophosphate, which is 
further phosphorylated to active metabolites gemcitabine diphosphate and 
gemcitabine triphosphate. Gemcitabine diphosphate inhibits DNA synthesis by 
inhibiting ribonucleotide reductase; gemcitabine triphosphate incorporates into 
DNA and inhibits DNA polymerase. 
 
15.32 Formulation: Commercially available for injection: 
Powder for reconstitution: 200 mg and 1 gram vials. 
Solution for injection: 38 mg/mL 200 mg, 1 gm, and 2 gm vials. MUST BE 
DILUTED BEFORE USE. 
 
15.33 Preparation, storage, and stability:  
Powder for reconstitution: 
Store intact vials at room temperature. Reconstitute the 200 mg vial with 
preservative free 0.9% NaCl 5 mL or the 1000 mg vial with preservative free 
0.9% NaCl 25 mL. Resulting solution is 38 mg/mL. Dilute with 50-500 mL 0.9% 
NaCl or D5W to concentrations as low as 0.1 mg/mL. Reconstituted vials are 
stable for up to 35 days and infusion solutions diluted in 0.9% NaCl are stable up 
to 7 days at 23ºC when protected from light; however, the manufacturer 
recommends use with 24 hours for both reconstituted vials and infusion 
solutions. Do not refrigerate. 
Solution for injection: 
Store intact vials at refrigeration temperature between 2º to 8ºC (36º to 46ºF). Do 
not freeze. Each vial contains a gemcitabine concentration of 38 mg/mL. The 
appropriate amount of drug should be further diluted with 50-500 mL 0.9% 
NaCL or D5W to concentrations as low as 0.1 mg/mL. When prepared as 
directed, diluted gemcitabine solutions are stable for 24 hours at controlled room 
temperature.  
15.34 Administration:  Refer to the drug treatment section of the protocol for specific 
administration directions and infusion rates. Gemcitabine is normally infused IV 
over 30 minutes. Note: Prolongation of the infusion time > 60 minutes has been 
shown to increase toxicity. Gemcitabine is being investigated in clinical trials for 
fixed dose rate infusion administration at doses from 1000 mg/m2 to 2200 mg/m2 
at a rate of 10 mg/m2/minute. Prolonged infusion times increase the accumulation 
of the active metabolite, gemcitabine triphosphate. Patients who receive 
gemcitabine fixed dose rate infusions experience more grade three and four 
hematologic toxicities.  
15.35 Pharmacokinetic information: 
Distribution: Infusions <70 minutes: 50 L/m2; Long infusion times: 370 
L/m2 
Protein binding: Low 
Metabolism: Metabolized intracellularly by nucleoside kinases to the 
active diphosphate (dFdCDP) and triphosphate (dFdCTP) nucleoside 
metabolites 
 
 

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Half-life elimination:  
Gemcitabine: Infusion time ≤hour: 32-94 minutes; infusion time 3-4 hours: 
4-10.5 hours 
Metabolite (gemcitabine triphosphate), terminal phase: 1.7-19.4 hours 
Time to peak, plasma: 30 minutes after completion of infusion 
Excretion: Urine (92% to 98%; primarily as inactive uridine metabolite); 
feces (<1%) 
 
15.36 Potential Drug Interactions:   
Increased Effect/Toxicity: Gemcitabine may increase the levels/effects of 
fluorouracil. Gemcitabine may enhance the adverse pulmonary effects of 
bleomycin. 
Ethanol/Nutrition/Herb Interactions Ethanol: Avoid ethanol (due to GI 
irritation). 
 
15.37 Known potential adverse events: Consult the package insert for the most 
current and complete information.  
Common known potential toxicities, > 10%:   
Cardiovascular: Peripheral edema, edema 
Central nervous system: Pain, fever, somnolence 
Dermatologic: Rash, alopecia, pruritus 
Gastrointestinal: Nausea/vomiting, constipation, diarrhea, stomatitis 
Hematologic: Anemia, leukopenia, thrombocytopenia, neutropenia, 
hemorrhage, myelosuppression is the dose-limiting toxicity 
Hepatic: Transaminases increased, alkaline phosphatase increased, 
bilirubin increased 
Renal: Proteinuria, hematuria, BUN increased 
Respiratory: Dyspnea 
Miscellaneous: Flu-like syndrome, infection 
 
Less common known potential toxicities, 1% - 10%:  
Local: Injection site reactions 
Neuromuscular & skeletal: Paresthesia 
Renal: Creatinine increased 
Respiratory: Bronchospasm 
 
Rare known potential toxicities, <1% (Limited to important or life-
threatening):  
Adult respiratory distress syndrome, anaphylactoid reaction, anorexia, 
arrhythmias, bullous skin eruptions, cellulitis, cerebrovascular accident, 
CHF, chills, cough, desquamation, diaphoresis, gangrene, GGT increased, 
headache, hemolytic uremic syndrome (HUS), hepatotoxic reaction, 
hypertension, insomnia, interstitial pneumonitis, liver failure, malaise, MI, 
peripheral vasculitis, Petechiae, pulmonary edema, pulmonary fibrosis, 
radiation recall, renal failure, respiratory failure, rhinitis, sepsis, 
supraventricular arrhythmia, weakness 
 
15.38 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
 
 

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15.39 Nursing Guidelines:  
 
15.391 
Monitor CBC, differential, PLTs prior to each dose. Myelosuppression 
is the principal dose-limiting factor. Modification may be considered 
by physician when bone marrow suppression is suspected. 
 
15.392 
Evaluate hepatic and renal function prior to initiation of therapy and 
periodically thereafter.  Closely observe those patients with a history of 
preexisting mild renal impairment or hepatic insufficiency.  Encourage 
hydration. 
 
15.393 
GEMZAR clearance is affected by age and gender.  Grade 3/4 
thrombocytopenia has been more common in elderly women. 
 
15.394 
Antiemetics may be required for probable mild to moderate nausea and 
vomiting. Assess for their effectiveness. 
 
15.395 
Instruct patient in management of possible mild diarrhea and 
stomatitis. 
 
15.396 
GEMZAR may cause fever in the absence of clinical infection.  Fever 
can be accompanied by other flu-like symptoms.  Instruct patient to 
report fever or flu-like symptoms to healthcare team.  Treat symptoms 
as they occur. 
 
15.397 
Macular or finely granular maculopapular eruptions were experienced 
by 30% of patients tested.  Instruct patients to report any skin changes. 
 
15.398 
Instruct patient to report any respiratory changes. 
 
15.399 
Burning may occur at the injection site. May apply heat during 
infusion to minimize pain. 
 
15.4 
Topotecan (Hycamtin®) 
15.41 Background: Topotecan binds to topoisomerase I and stabilizes the cleavable 
complex so that relegation of the cleaved DNA strand cannot occur. This results 
in the accumulation of cleavable complexes and single-strand DNA breaks. 
Topotecan acts in S phase of the cell cycle. 
 
15.42 Formulation: Commercially available Injection, powder for reconstitution, as 
hydrochloride: 4 mg [base] 
 
15.43 Preparation, storage, and stability: Store intact vials at room 
temperature and protect from light. Reconstitute with 4 mL Sterile Water 
for Injection. This solution is stable for up to 28 days at room temperature. 
Topotecan should be further diluted in 50-100 mL of D5W or 0.9% 
Sodium Chloride. Refer to the treatment section for final dilution volume. 
This solution is stable for 24 hours at room temperature or up to 7 days 
under refrigeration.  
 

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15.44 Administration:  Administer IV piggyback over 30 minutes or by 24-hour 
continuous infusion. See specific administration instructions in the treatment 
section of the protocol. 
 
15.45 Pharmacokinetic information: 
Distribution: Vdss of the lactone is high (mean: 87.3 L/mm2; range: 25.6-
186 L/mm2), suggesting wide distribution and/or tissue sequestering 
Protein binding: ~35% 
Metabolism: Undergoes a rapid, pH-dependent hydrolysis of the lactone 
ring to yield a relatively inactive hydroxyl acid in plasma; metabolized in 
the liver to N-demethylated metabolite 
Half-life elimination: I.V.: 2-3 hours; renal impairment: 5 hours; 
Excretion: I.V.: Urine (51%; 3% as N-desmethyl topotecan); feces (18%; 
2% as N-desmethyl topotecan) 
 
15.46 Potential Drug Interactions:   
Increased Effect/Toxicity: Filgrastim may cause prolonged and sever 
neutropenia and thrombocytopenia if administered concurrently with 
topotecan; initiate filgrastim at least 24 hours after topotecan. Platinum 
derivatives (carboplatin, cisplatin, oxaliplatin) may enhance the 
adverse/toxic effects of topotecan; monitor for hematologic toxicity, 
especially if the platinum derivative is administered prior to topotecan. 
 
15.47 Known potential adverse events: Consult the package insert for the most 
current and complete information including U.S. Boxed Warnings 
pertaining to severe diarrhea and severe myelosuppression. 
 
Common known potential toxicities, > 10%:   
Central nervous system: Fatigue, fever, pain, headache 
Dermatologic: Alopecia, rash 
Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain, 
anorexia, stomatitis 
Hematologic: Neutropenia, leukopenia, anemia, thrombocytopenia, 
neutropenic fever/sepsis 
Neuromuscular & skeletal: Weakness 
Respiratory: Dyspnea, cough 
 
Less common known potential toxicities, 1% - 10%:  
Hepatic: Transient increase in liver enzymes 
Neuromuscular & skeletal: Paresthesia 
Miscellaneous: Sepsis 
 
Rare known potential toxicities, <1% (Limited to important or life-
threatening):  
Abdominal pain, allergic reactions, anaphylactoid reactions, angioedema, 
bleeding (severe, associated with thrombocytopenia), dermatitis (severe), 
injection site reactions (mild erythema, bruising), neutropenic colitis, 
pancytopenia, pruritus (severe) 
 
15.48 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 

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15.49 Nursing Guidelines:  
 
15.491 Monitor CBC. The dose-limiting toxicity is leukopenia. WBC count 
decreases with increasing doses. When drug is administered at 
1.5 mg/m2/day for 5 days, an 80-90% decrease in WBC count at nadir is 
typically seen after the first cycle. 
 
15.492 Neutropenia is not cumulative. Grade 4 neutropenia (<500 cells/mm3) is 
most common during the first cycle (60% of the patients) and occurs in 
approximately 39% of all cycles, with a median duration of 7 days. 
Nadir occurs at approximately the median of 12 days. Sepsis is possible. 
Watch for profound neutropenia and instruct patient in low count 
precautions and to report signs of infection to health care team 
immediately. 
 
15.493 Monitor PLT count. Grade 4 thrombocytopenia (<25,000/mm3) occurs 
in approximately 27% of patients and in 9% of cycles, with a median 
duration of 5 days and platelet nadir at a median of 15 days. Platelet 
transfusion may be needed. Instruct patient to report any unusual 
bleeding or bruising. 
 
15.494 Monitor HGB. Grade 3-4 anemia occurs in approximately 37% of 
patients and in 14% of cycles. Median nadir is seen at Day 15. 
Transfusions have been needed in approximately 50% of patients. 
 
15.495 Myelosuppression can be more severe when drug is given with cisplatin. 
 
15.496 Nausea is experience by approximately 65% of patients, vomiting is 
experienced by approximately 45% and diarrhea by approximately 30%. 
Premedicate with anti-emetics and monitor for their effectiveness. 
Administer anti-diarrheals as indicated. Assess status. 
 
15.497 Encourage paced activities and frequent rest periods to deal with the 
fatigue which is experienced by approximately 30% of patients. 
 
15.498 Approximately 28% of patients experience stomatitis. Advise patient in 
cryotherapy preventive measures, try treating with vitamin E oil if 
stomatitis occurs. 
 
15.499a Monitor LFTs and renal function. Dose reductions may be necessary in 
those with hepatic and renal dysfunction. 
 
15.499b Advise patients of possible reversible alopecia which has been seen in 
49% of patients. 
 
 
 

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15.5 
Paclitaxel (Taxol®) 
15.51 Background: Antineoplastic Agent, Antimicrotubular, Taxane derivative. 
Paclitaxel promotes microtubule assembly by enhancing the action of tubulin 
dimers, stabilizing existing microtubules, and inhibiting their disassembly, 
interfering with the late G2 mitotic phase, and inhibiting cell replication. In 
addition, the drug can distort mitotic spindles, resulting in the breakage of 
chromosomes. Paclitaxel may also suppress cell proliferation and modulate 
immune response. 
 
15.52 Formulation: Commercially available for injection 6 mg/mL (5 mL, 16.7 mL, 25 
mL, and 50 mL) [contains alcohol and purified Cremophor EL (polyoxyethylated 
castor oil)]. 
 
15.53 Preparation, storage, and stability: Refer to package insert for complete 
preparation and dispensing instructions. Store intact vials at room 
temperature and protect from light. Dilute in 250-1000 mL D5W or 0.9% 
NaCL to a concentration of 0.3 – 1.2 mg/mL. Solutions in D5W and 0.9% 
NaCl are stable for up to 3 days at room temperature. Chemotherapy 
dispensing devices (e.g., Chemo Dispensing Pin) should not be used to 
withdraw paclitaxel from the vial. 
Paclitaxel should be dispensed in either glass or non-PVC containers (e.g., 
Excel/PAB). Use nonpolyvinyl (non-PVC) tubing (e.g., polyethylene) to 
minimize leaching.  
 
15.54 Administration: Infuse IV over 1-96 hours. When administered as sequential 
infusions, taxane derivatives should be administered before platinum derivatives 
(cisplatin, carboplatin) to limit myelosuppression and to enhance efficacy. Infuse 
through a 0.22 micron in-line filter and nonsorbing administration set. 
 
15.55 Pharmacokinetic information: 
Distribution: Vd: Widely distributed into body fluids and tissues; affected 
by dose and duration of infusion 
Vdss: 1- to 6-hour infusion: 67.1 L/m2 
Vdss: 24-hour infusion: 227-688 L/m2 
Metabolism: Hepatic via CYP2C8 and 3A4; forms metabolites (primarily 
6α-hydroxypaclitaxel). 
Half-life elimination: 1- to 6-hour infusion: Mean (beta): 6.4 hours, 
3-hour infusion: Mean (terminal): 13.1-20.2 hours 
24-hour infusion: Mean (terminal): 15.7-52.7 hours 
Excretion: Feces (~70%, 5% as unchanged drug); Urine (14%) 
Clearance: Mean: Total body: After 1- and 6-hour infusions: 5.8-16.3 
L/hour/m2; after 24-hour infusions: 14.2-17.2 L/hour/m2 
 
15.56 Potential Drug Interactions:   
Cytochrome P450 Effect: Substrate (major) of CYP2C8, CYP3A4; 
Induces CYP3A4 (weak).  
Increased Effect/Toxicity: CYP2C8 inhibitors may increase the 
levels/effects of paclitaxel. Refer to the package insert or LexiComp1 for 
example inhibitors. 

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Decreased Effect: CYP2C8 inducers may decrease the levels/effects of 
paclitaxel. Refer to the package insert or LexiComp1 for example inducers. 
Herb/Nutraceutical Interactions: Avoid black cohosh, dong quai in 
estrogen-dependent tumors. Avoid valerian, St John’s wort (may decrease 
paclitaxel levels), kava kava, gotu kola (may increase CNS depression). 
 
15.57 Known potential adverse events: Consult the package insert for the most 
current and complete information. Percentages reported with single-agent 
therapy. U.S. Boxed Warning: Bone marrow suppression is the dose-
limiting toxicity; do not administer if baseline absolute neutrophil count 
(ANC) is <1500 cells/mm3 (1000 cells/mm3 for patients with AIDS-related 
KS); reduce future doses by 20% for severe neutropenia. U.S. Boxed 
Warning: Severe hypersensitivity reactions have been reported. 
Common known potential toxicities, >10%:   
Cardiovascular: Flushing, ECG abnormal, edema, hypotension. 
Dermatologic: Alopecia, rash. 
Gastrointestinal: Nausea/vomiting, diarrhea, mucositis, stomatitis, 
abdominal pain (with intraperitoneal paclitaxel)  
Hematologic: Neutropenia, leukopenia, anemia, thrombocytopenia, 
bleeding. 
Hepatic: Alkaline phosphatase increased, AST increased. 
Local: Injection site reaction (Erythema, tenderness, skin discoloration, 
swelling). 
Neuromuscular & skeletal: Peripheral neuropathy, arthralgia, myalgia, 
weakness. 
Renal: Creatinine increased. 
Miscellaneous: Hypersensitivity reaction, infection. 
Less common known potential toxicities, 1% - 10%:  
Cardiovascular: Bradycardia, tachycardia, hypertension, rhythm 
abnormalities, syncope, venous thrombosis. 
Dermatologic: Nail changes. 
Hematologic: Febrile neutropenia. 
Hepatic: Bilirubin increased. 
Respiratory: Dyspnea. 
Rare known potential toxicities, <1% (Limited to important or life-
threatening):  
Anaphylaxis, ataxia, atrial fibrillation, AV block, back pain, cardiac 
conduction abnormalities, cellulitis, CHF, chills, conjunctivitis, 
dehydration, enterocolitis, extravasation recall, hepatic encephalopathy, 
hepatic necrosis, induration, intestinal obstruction, intestinal perforation, 
interstitial pneumonia, ischemic colitis, lacrimation increased, 
maculopapular rash, malaise, MI, necrotic changes and ulceration 
following extravasation, neuroencephalopathy, neutropenic enterocolitis, 
ototoxicity, pancreatitis, paralytic ileus, phlebitis, pruritus, pulmonary 
embolism, pulmonary fibrosis, radiation recall, radiation pneumonitis, 
pruritus, renal insufficiency, seizure, skin exfoliation, skin fibrosis, skin 
necrosis, Stevens-Johnson syndrome, supraventricular tachycardia, toxic 
epidermal necrolysis, ventricular tachycardia  (asymptomatic), visual 
disturbances. 

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15.58 Drug procurement:  Commercial supplies. Pharmacies or clinics shall obtain 
supplies from normal commercial supply chain or wholesaler. 
 
15.59 Nursing Guidelines:  
 
15.591 
Premedicate with steroids, antihistamines, and H2 blockers as per 
institutional guidelines. 
15.592 
Mix the infusion bag well.  Thorough admixture of this drug often 
prevents a hypersensitivity reaction.  An inline filter of <0.22 micron 
must be used distal to the infusion pump.  Filter may need to be 
changed if infusion is to be prolonged >12 hours. Inspect solution for 
excessive particulate matter, if present do not use. 
 
15.593 
Caution patients that the alcohol contained in the infusion may cause 
impairment in operating heavy equipment or in driving a vehicle and to 
assess their ability before trying either. Advise avoidance of any 
alcohol or depressants such as sedatives and opiates if not necessary. 
 
15.594 
Assess the patient frequently for the first 30 minutes. Taxol® 
hypersensitivity reactions, which may include chest pain, back pain, 
flushing, diaphoresis, dyspnea, pruritus, hypotension, hypertension, 
bronchospasm and/or urticaria, usually occur early in the infusion.  
Have the anaphylaxis tray available. 
 
15.595 
If a reaction occurs, stop the infusion immediately. Epinephrine, IV 
fluids, diphenhydramine, and methylprednisolone may be used as per 
MD’s order. 
 
15.596 
Approximately 60% of patients experience peripheral sensory 
neuropathy (numbness, tingling, burning pain, fine motor skills 
impairment, paresthesias, distal sensory loss). Patients receiving higher 
doses at shorter infusion times are at greater risk. Most cases have been 
reported at doses >170 mg/m2/day and with cumulative doses over 
multiple courses of therapy.  The nerve damage may take months to 
resolve. Nonsteroidal anti-inflammatory agents and opiates have not 
been effective in treating neuropathic pain. Consult MD about trying 
tricyclic antidepressants or possibly Neurontin. 
 
15.597 
Increased risk of cardiotoxicity when given in combination with 
doxorubicin, with a sharp increase in risk of CHF once cumulative 
dose of doxorubicin is >380 mg/m2. At this point Taxol should be 
continued as a single agent only. Monitor for sign/symptoms of CHF. 
Instruct patient to report any swelling in the hands, arms, feet, or legs, 
and any chest pain. 
 
15.598 
Mucositis can usually be managed with a salt and soda mouthwash (1 
tsp. Salt, 1 tsp. Soda and 1 quart boiled water) or try OTC oral Lysine 
or Vitamin E. 
 

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15.599a Narcotics and nonsteroidal anti-inflammatory drugs may be used to 
manage the myalgias. 
 
15.599b Monitor CBC closely. Neutropenia is most severe in patients who have 
had previous chemotherapy. Instruct patient to report signs or 
symptoms of infection, unusual bruising or bleeding to the health care 
team. 
 
15.599c There is an increased risk of neutropenia and stomatitis when given 
prior to doxorubicin. Therefore Taxol should always be given after 
doxorubicin administration. 
 
15.599d Monitor IV site closely and establish patency before administration. 
Paclitaxel is an irritant, however rarely rash, radiation recall, and 
ulceration have occurred with infiltration of drug. 
 
15.599e Monitor liver function tests. 
 
15.599f Inform patient about total alopecia. 
 
15.599g If given on the same day as a platinum agent, paclitaxel should be 
administered first to limit myelosuppression and enhance efficacy of 
agent. 
 
15.6 
Bevacizumab 
15.61 Background 
Bevacizumab is classified as an Anti-VEGF Monoclonal Antibody and a 
Vascular Endothelial Growth Factor (VEGF) Inhibitor. Bevacizumab is a 
recombinant, humanized monoclonal immunoglobulin G1 (IgG1) antibody which 
binds to, and neutralizes, vascular endothelial growth factor (VEGF), preventing 
its association with endothelial receptors, Flt-1 and KDR. VEGF binding initiates 
angiogenesis (endothelial proliferation and the formation of new blood vessels). 
The inhibition of microvascular growth is believed to retard the growth of all 
tissues (including metastatic tissue).  
15.62 Formulation 
Commercially available for injection 25 mg/mL (4 mL, 16 mL). 
15.63 Preparation, storage, and stability 
Refer to package insert for complete preparation and dispensing instructions. 
Store intact vials at refrigeration temperature (2ºC to 8ºC), protect from light, do 
not freeze or shake. Prior to infusion, dilute prescribed dose of bevacizumab in 
100 mL 0.9% NaCl. Do not mix with dextrose-containing solutions. Diluted 
solutions are stable for up to 8 hours under refrigeration. 
15.64 Administration   
IV infusion, usually after the other antineoplastic agents. Refer to treatment 
section for specific order of administration. Infuse the initial dose over 90 
minutes. Infusion may be shortened to 60 minutes if the initial infusion is well 

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tolerated. The third and subsequent infusions may be shortened to 30 minutes if 
the 60-minute infusion is well tolerated. Monitor closely during the infusion for 
signs/symptoms of an infusion reaction. Some institutions use a 10-minute 
infusion (0.5 mg/kg/minute) for bevacizumab dosed at 5 mg/kg. 
15.65 Pharmacokinetic information 
Distribution: Vd: 46 mL/kg (limited extravascular distribution) 
Half-life elimination: ~20 days (range: 11-50 days) 
Clearance: 2.75-5 mL/kg/day. A low serum albumin and high tumor 
burden increase clearance by 30% and 7% respectively.  Clearance 
increases with increasing body weight, and is 15% slower in women than 
men. 
Time to steady state: 100 days 
15.66 Potential Drug Interactions   
Increased Effect/Toxicity: Bevacizumab may increase the levels/effects of 
anthracyclines, Irinotecan, Sorafenib, and Sunitinib. Serum concentrations 
of irinotecan’s active metabolite may be increased by bevacizumab; an 
approximate 33% increase has been observed. 
15.67 Known potential adverse events 
Consult the package insert for the most current and complete information. 
U.S. Boxed Warnings include severe or fatal hemorrhage, including 
hemoptysis, gastrointestinal bleeding, central nervous system hemorrhage, 
epistaxis, and vaginal bleeding. Avoid use in patients with serious 
hemorrhage or recent hemoptysis. Percentages reported as Monotherapy 
and as part of combination chemotherapy regimens.  
Common known potential adverse events, >10%: 
Cardiovascular: Hypertension, thromboembolic events, hypotension. 
Central nervous system: Pain, headache, dizziness, fatigue, sensory 
neuropathy. 
Dermatologic: Alopecia, dry skin, exfoliative dermatitis, skin 
discoloration. 
Endocrine & metabolic: Hypokalemia. 
Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, 
stomatitis, gastrointestinal hemorrhage, dyspepsia, taste disorder, 
flatulence, nausea, vomiting, weight loss. 
Hematologic: Hemorrhage, neutropenia, leukopenia. 
Neuromuscular & skeletal: Weakness, myalgia, back pain. 
Ocular: Tearing increased. 
Renal: Proteinuria. 
Reproductive system and breast disorders: Ovarian failure, vaginal 
hemorrhage. As an IgG1, bevacizumab may be secreted in human milk. 
Women should avoid breast feeding. 
Respiratory: Upper respiratory infection, epistaxis, dyspnea, rhinitis 
Miscellaneous: Infection, pneumonia, catheter infection, wound infections. 
Less common known potential adverse events, 1% - 10%:  
Cardiovascular: DVT, venous thrombus/embolus, arterial thrombosis, 
syncope, intra-abdominal venous thrombosis, cardio-/cerebrovascular 

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arterial thrombotic event, CHF, left ventricular dysfunction, 
supraventricular tachycardia. 
Central Nervous System: Confusion, abnormal gait, CNS hemorrhage, 
reversible posterior leukoencephalopathy syndrome (RPLS), syncope 
Dermatologic: Acne, nail disorder, pruritus, rash desquamation, skin ulcer, 
urticaria, and wound dehiscence. 
Ear and labyrinth disorders: Vertigo 
Endocrine& metabolic: Dehydration, hyperglycemia, hyponatremia.   
Gastrointestinal: Xerostomia, colitis, ileus, gingivitis, fistula, 
gastroesophageal reflux, gastrointestinal perforation, intra-abdominal 
abscess, mouth ulceration, tooth abscess, gastritis, gingival pain, ileus, 
gastrointestinal ulcer 
Genitourinary: Polyuria/urgency, vaginal hemorrhage. 
Hematologic: Anemia, febrile neutropenia/infection, thrombocytopenia, 
decreased hemoglobin, increased prothrombin time  
Hepatic: Bilirubinemia. 
Nervous system disorders: Peripheral sensory neuropathy 
Neuromuscular & skeletal: Bone pain  
Renal: Acute kidney injury, hematuria 
Respiratory: Voice alteration (hoarseness), cough, pneumonitis/pulmonary 
infiltrates, hemoptysis, pulmonary embolism 
Miscellaneous: Infusion reactions may include rash, urticaria, fever, rigors, 
hypertension, hypotension, wheezing, or hypoxia. Anaphylactic and 
anaphylactoid-type reactions.  
Rare known potential adverse events, <1% (Limited to important or 
life-threatening):  
Anastomotic ulceration, angina, cerebral infarction, gall bladder 
perforation, hemorrhagic stroke, hypertensive crises, hypertensive 
encephalopathy, intestinal necrosis, intestinal obstruction, mesenteric 
venous occlusion, microangiopathic hemolytic anemia (when used in 
combination with Sunitinib), acute coronary syndrome, heart failure, 
myocardial infarction, ventricular arrhythmia, ventricular fibrillation, nasal 
septum perforation, nephrotic syndrome, renal failure, pancytopenia, 
polyserositis, pulmonary hemorrhage, pulmonary hypertension, renal 
failure, renal thrombotic microangiopathy, subarachnoid hemorrhage, 
toxic anterior segment syndrome, transient ischemic attack, ureteral 
stricture, wound healing complications 
15.68 Drug procurement 
Commercial supplies. Pharmacies or clinics shall obtain supplies from normal 
commercial supply chain or wholesaler. 
15.69 Nursing Guidelines  
15.591 
Monitor patients closely for infusion type reactions, including fever, 
chills, myalgias, rigors, or other allergic reactions.  While this is less 
likely given that bevacizumab is a humanized antibody, there still 
exists the potential for severe allergic reactions.  If these signs or 
symptoms occur stop the infusion immediately and contact MD.  Have 
emergency equipment nearby and be prepared to administer emergency 
treatment as ordered by MD. 

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15.692 
Monitor urine dipstick or UPC as required by the test schedule 
 
15.693 
Evaluate IV site regularly for signs of infiltration. 
 
15.694 
Bleeding in the absence of thrombocytopenia is a dose limiting 
toxicity.  Monitor patient closely for hemorrhagic events, including 
CNS hemorrhage, epistaxis, hematemesis and hemoptysis.  Most cases 
of bleeding have occurred at the tumor site.  Advise patient about the 
potential for bleeding or thrombosis. 
 
15.695 
In patients receiving treatment for lung cancer, hemoptysis and 
pulmonary hemorrhage occurred in up to 10% of patients in one study.  
Monitor these patients especially closely.  
 
15.696 
Patient may experience Grade 1-2 nausea, however vomiting is 
uncommon.  Medicate as ordered and monitor for effectiveness.  
 
15.697 
Monitor for skin rash, instruct patient to report to MD. 
 
15.698  
Monitor blood pressure.  Administer antihypertensives as ordered by 
MD. 
  
15.699a  Monitor for signs and symptoms of deep vein thrombosis (DVT) or 
pulmonary embolism (PE), or myocardial infarction (MI) including 
new or worsening angina.  These have been reported with therapy.  
Instruct patient to report any calf pain, chest pain or shortness of breath 
to MD immediately.  
 
15.699b  Asthenia and headache were reported commonly during therapy (in up 
to 70% and 50% of patients respectively).  Administer acetaminophen 
as needed.  Monitor for its effectiveness.  Avoid the use of aspirin, or 
ibuprofen as this may interfere with the coagulation cascade and 
further add to the risk of bleeding. 
 
15.699c  Monitor CBC, including platelets.  Instruct patient to report signs and 
symptoms of infection, unusual bruising or bleeding to the MD. 
  
15.699d  Patients receiving warfarin therapy for thrombosis should have their 
PT or INR monitored weekly until two stable therapeutic levels are 
attained.  For patients on warfarin for venous access prophylaxis, 
routine monitoring is satisfactory. 
 
15.699e  A rare but serious complication of bevacizumab is wound dehiscence.  
Patients who have had recent surgery or have other open wounds 
should be monitored carefully. 
 
15.699f  Gastrointestinal perforation with or without abdominal abscess is rare 
but possible.  This may present itself as vague abdominal pain 
associated with constipation and vomiting.  Instruct patient to report 
abdominal pain to the MD.  

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15.699g  Reversible Posterior Leukoencephalopathy Syndrome (RPLS) is a 
rare (<1%) but serious condition.  Presenting symptoms may include 
changes in mental status, visual disturbance, seizure, or other CNS 
changes.  Patients with this syndrome generally had HTN as well, 
therefore BP monitoring is important.  Instruct patient to report any 
mental status changes, visual changes, seizures, or other CNS changes 
to the MD immediately.  These may be a sign of RPLS or more 
serious condition, such as hemorrhagic event in the CNS.  
 
15.699h  Warn female patients of the possibility of ovarian failure and 
subsequent infertility. Vaginal hemorrhage is also possible. Instruct 
patients to report any heavy or unusual vaginal bleeding to health care 
team. 
 
16.0 
Statistical Considerations and Methodology 
16.1 
Study Overview 
This randomized Phase II trial will compare the OS in patients with ovarian cancer who 
received MV-NIS to patients who received investigator’s choice chemotherapy 
(liposomal doxorubicin, gemcitabine, topotecan, or paclitaxel). This trial implements one 
interim futility analysis.  
16.2 
Primary Endpoint 
16.21 The proposed immune response mechanism of action for MV-NIS may result in a 
long-term survival benefit after disease progression. The primary endpoint is OS 
as defined as the time from registration/randomization to death due to all causes. 
OS is measured from randomization rather than start of study therapy as the 
surgery for port placement is considered a necessary prerequisite to the MV-NIS 
treatment. 
16.22 All patients who meet the eligibility criteria, sign the consent form, and are 
randomized will be considered evaluable for estimation of OS. 
16.3 
Primary Analysis 
The primary goal is to compare MV-NIS versus investigator’s choice chemotherapy, 
where the alternative hypothesis is that the MV-NIS has improved OS compared to 
investigator’s choice.  We will enter 60 evaluable patients to the study using a 2:1 
randomization scheme (40 MV-NIS and 20 cytotoxic chemotherapy), unless the study is 
stopped early at the time of the interim futility analysis (see below).  
With 60 evaluable patients per arm, we have 80% power to detect an improvement for 
MV-NIS in the median OS from 14 to 26.5 months (hazard ratio (HR)=0.53), assuming a 
1-sided significance level of 0.15 (30) and an accrual rate of 3 patients per month. The 
primary analysis will be a comparison the MV-NIS versus investigator’s choice 
chemotherapy using a one-sided log-rank test, where a HR<0.715 in favor of MV-NIS is 
needed to reject the null hypothesis. This final analysis will take place after 44 total 
events have occurred across both arms combined (which should happen after about 30 
months of follow-up in all evaluable patients). 

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The primary efficacy model will be stratified by all the stratification factors for this 
study. 
16.4 
Interim Futility Analysis 
16.41  The interim futility analysis will happen after 22 events are observed across both 
arms combined. The interim futility boundary was selected using EAST software. 
We selected a Rho family "Beta" spending function with rho parameter "equal" 
1.3. To reject the alternative hypothesis at the interim analysis (i.e. reject the 
measles virus as promising), the HR will need to be ≥1 for the MV-NIS versus 
investigator’s choice chemotherapy, which corresponds to a 1-sided (30) p-value 
≥0.50. If the HR is less than 1 (1-sided p <0.50), the study will continue to full 
accrual and the final analysis will be conducted as discussed above.  
16.42 The study will not stop accrual at the time of the interim analysis, unless undue 
toxicity or a higher than expected accrual rate is observed. 
16.5 
Secondary Analysis Plans 
16.51 (Goal 2.21):  
16.511 PFS is defined as the time from start of study therapy to the date of first 
observation of disease progression or death due to any cause (whichever 
comes first). The distribution of PFS for both arms of the study will be 
estimated using the Kaplan-Meier method, and be compared using a one-
sided logrank test. 
16.512  OS at 12 months (OS12) and PFS at 6 months (PFS6) distributions both 
arms of the study will be estimated using the Kaplan-Meier method, and 
be compared using a one-sided logrank test. 
16.513 A confirmed tumor response is defined to be a CR or PR noted as the 
objective status on 2 consecutive evaluations at least 4 weeks apart. All 
patients meeting the eligibility criteria who have signed a consent form 
and have begun treatment will be evaluable for response. Objective 
response rates (ORR) will be compared between treatment arms using 
chi-square or fisher exact methodology as appropriate. 
16.52 (Goal 2.22):  Safety and tolerability of MV-NIS 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. 
16.53 (Goal 2.23):  Quality of life as measured by the FACT-Ov 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 QOL. Patient 
demographics, baseline prognostic factors and other confounding variables may 
be considered as covariates for further exploration. Population-level and subject-
level longitudinal plots will be plotted to display the trend of patient reported 
QOL. 

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16.6 
Translational Endpoints 
16.61  (Goals 2.31-2.35): Translational endpoints are numerous. All analyses with 
respect to the translational endpoints of this study are intended to be hypothesis-
generating and descriptive in nature. Data will be gathered for a number of 
laboratory correlative variables as described in the goals for each patient. 
Descriptive statistics and simple scatterplots 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). 
16.62 Supplementary analysis of select endpoints may include subset analyses 
according to descriptive and stratification factors. 
16.7 
Sample Size, Accrual Time and Study Duration 
16.71 Patients who are Pre-Registered but fail to meet criteria for successful surgical 
placement of an interperitoneal port, will not be registered or randomized to this 
trial and will not count towards the accrual. 
16.72 A maximum of 60 evaluable patients will be accrued onto this randomized phase 
II study unless the study is closed early for excessive toxicity or lack of efficacy. 
We anticipate accruing an additional 10% of patients to account for ineligibility, 
cancellation, major treatment violation, or other reasons.  Therefore, maximum 
accrual is about 66 patients. The expected accrual rate is about 3 patients per 
month. With this accrual rate, we expect to finish accrual within about 22 
months. We anticipate that the study will take approximately 60 months to 
complete. This allows a 30-month follow-up for the final patient enrolled, along 
with data entry and analysis. 
16.73 For purpose of Clinicaltrails.gov reporting, the Primary Endpoint Completion 
Date (PECD) for this study is the time the last patient registered has been 
followed for at least 26 months. 
16.8 
Adverse Events Stopping Rule 
Within arm A, a specific interim toxicity analysis will be performed once at least 20 
evaluable patients have been followed for 3 months (accrual will not stop during this 
three-month time period). Accrual will be temporarily suspended if at any time we 
observe events considered at least possibly related to study treatment (i.e. an adverse 
event with attribute specified as “possible”, “probable”, or “definite”) that satisfy either 
of the following : 
If 3 or more patients in the first 20 treated patients (or 15% or more after 20 
patients have been accrued) experience a grade 4 or higher nonhematologic 
adverse event. 
16.9a 
Accrual Monitoring Stopping Rule 
Given the expected accrual rate is around 3 patients per month, it is expected that the 
study will take around 3.5 years to fully accrue. We plan to monitor the accrual 
continually and if we only end up accruing 15 patients or less in the first year (after study 
activation), we will consider stopping the trial for slow accrual. 
 

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16.9b Study Monitoring 
16.9b1 This study will be monitored by the Mayo Clinic Data Safety Monitoring Board 
(DSMB). Reports containing patient characteristics, toxicity and administrative 
information will be provided to the DSMB every three months, with the first 
report due at the first reporting period after study initiation. Reports will be due 
January 31 and July 31 or April 30 and October 31, unless otherwise specified by 
the DSMB. 
16.9b2   This study will be monitored by the Clinical Data Update System (CDUS) 
version 2.0. A full report containing cumulative CDUS data will be submitted 
quarterly to CTEP by electronic means. Reports are due January 31, April 30, 
July 31, and October 31. 
16.9c  Minorities Distributions (sex, race, ethnicity) 
Accrual Targets 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
2 
0 
2 
Not Hispanic or Latino 
64 
0 
64 
Ethnic Category: Total of all subjects 
66 
0 
66 
Racial Category 
American Indian or Alaskan Native 
1 
0 
1 
Asian 
0 
0 
0 
Black or African American 
0 
0 
0 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
White 
65 
0 
65 
Racial Category: Total of all subjects 
66 
0 
66 
 
Ethnic 
Categories: 
Hispanic or Latino – a person of Cuban, Mexican, Puerto Rican, South or Central 
American, or other Spanish culture or origin, regardless of race. The term “Spanish 
origin” can also be used in addition to “Hispanic or Latino.” 
Not Hispanic or Latino 
Racial 
Categories: 
American Indian or Alaskan Native – a person having origins in any of the original 
peoples of North, Central, or South America, and who maintains tribal affiliations or 
community attachment. 
Asian – a person having origins in any of the original peoples of the Far East, 
Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, 
India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and 
Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific 
Islanders in previous data collection strategies.)  
Black or African American – a person having origins in any of the black racial 
groups of Africa. Terms such as “Haitian” or “Negro” can be used in addition to 
“Black or African American.” 
Native Hawaiian or other Pacific Islander – a person having origins in any of the 
original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. 
White – a person having origins in any of the original peoples of Europe, the Middle 
East, or North Africa. 

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17.0 
Pathology Considerations 
For Arm A patients, baseline tumor specimens obtained either at study entry (when feasible) or from previous surgery (when biopsy 
attempt is unsuccessful) will be examined for cellular immune infiltration, HLA-B7 expression, and have transcriptomic analysis 
performed (Next Gen) to characterize measles permissive signatures and immune signatures. 
 
17.1 
Summary Table of Research Tissue Specimens to be collected for this Protocol (Arm A and bulky disease patients only) 
 
Correlative Study 
(Section for more 
information) 
Mandatory 
or Optional 
Type of Tissue 
to Collect 
Block, Slides, Core, etc. (# of 
each to submit) 
Process at 
site? (Yes 
or No) 
Temperature & 
Conditions for 
Storage /Shipping 
Tumor biopsy (at 
time of debulking 
surgery and/or port 
placement) 
Mandatory 
Formalin Fixed 
(use archived 
sample if biopsy 
not obtained ) 
FFPE Block or 10 unstained 
FFPE slides (5 micron), 2 
unstained FFPE slides (10 
micron), 1 FFPE slide stained 
with hematoxylin and eosin 
Yes 
Ambient 
 
17.2 
Storage of pathology specimens 
Slides/blocks will be shipped to and stored in 
laboratory: 
 
 
 

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18.0 
Data Collection Procedures 
18.1 
Submission Timetable 
18.11 Initial Material(s) 
CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule Section 4.0) 
Preregistration Screening Failure 
At Pre-registration 
On-Study 
≤2 weeks after registration 
Baseline Adverse Event 
Laboratory Form Arm A Baseline 
Laboratory Form Arm B Baseline 
RECIST Measurement Form (Baseline) 
Research Submission Form Arm A Baseline  
Research Submission Form Arm B Baseline  
Concomitant Medication Form (Baseline)  
CA125 Form Baseline 
Booklet Compliance1 
Patient Questionnaire Booklet1 
Research Tissue Submission Arm A (Bulky and 
non-Bulky) and Arm B (Bulky) (Prior to 
Cycle 1) 
At peritoneal catheter implantation 
End of Active Treatment/Cancel Notification 
Submit ≤2 weeks after registration if 
withdrawal/refusal occurs prior to beginning 
protocol therapy 
1. Complete only when patient does not complete the Patient Reported Outcome Booklet containing the 
FACT-O. 
2. Patient questionnaire booklet must be used; copies are not acceptable for this submission. 
 
18.12 Test Schedule Material(s) 
CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule 
Section 4.0) 
At each evaluation 
during treatment 
At end of 
treatment 
Evaluation/Treatment Arm A – Cycle 1 
X 
X 
Evaluation/Treatment Arm A – Cycles 2 and All 
Subsequent Cycles 
X 
X 
Evaluation/Treatment Arm B 
X 
X 
CA125 Form 
X 
X 
RECIST Measurement  
X 
X 
Nadir/Adverse Event Arm A 
X 
X 
Nadir/Adverse Event Arm B 
X 
X 
Laboratory Form Arm A 
X 
X 
Laboratory Form Arm B 
X 
X 
Concomitant Medication  
X 
X 
Research Submission Form Arm A 
X (see Section 14.0) 
 

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CRF 
Active-Monitoring Phase 
(Compliance with Test Schedule 
Section 4.0) 
At each evaluation 
during treatment 
At end of 
treatment 
Research Submission Form Arm B 
X (see Section 14.0) 
 
End of Active Treatment/Cancel Notification  
 
X 
ADR/AER 
At each occurrence 
(see Section 10.0) 
 
Booklet Compliance1 
X 
X 
Patient Questionnaire Booklet2 
X 
X 
1. Complete only when patient does not complete the Patient Reported Outcome Booklet 
containing the FACT-O. 
2. Patient questionnaire booklet must be used; copies are not acceptable for this submission. 
 
18.13 Follow-up Material(s) 
CRF 
Event Monitoring Phase1 
Q 3 months 
until PD 
At PD 
After PD q.6 
months 
Death 
Event Monitoring 
X 
X 
X 
X 
1. If a patient is still alive 5 years after registration, no further follow-up is required, but one event 
monitoring form must be completed for all patients to record progression status. 
2. Note: Submit documentation of progression to the MCCC Operations Office, Attention QAS for 
MC1365 via 
 
 
 
19.0 
Budget Considerations 
19.1 
Costs charged to patient 
Routine clinical care.  
For patients randomized to Arm A, MV-NIS will be provided free of charge by Mayo.  
For patients randomized to Arm B (cytotoxic chemotherapy), DOXIL, GEM, TOPA, 
TAXOL, or bevacizumab, along with costs associated with infusion and monitoring, will 
be billed to the participant as conventional care. 
Rochester only: Participants randomized to Arm A will not be billed for room and board 
or nursing charges while at the Clinical Research and Trials Unit (CRTU). However, the 
participant may be billed for ancillary expenses such as any oral medications prescribed 
at the time of discharge. 
19.2 
Tests to be research funded 
Insertion of the intraperitoneal port, all pharmacological/correlative studies (covered by 
the Ovarian SPORE, the Schulze Foundation Study Budget, and the Minnesota Ovarian 
Cancer Alliance).  
Cytomel® (liothyronine sodium) or equivalent generic will be provided free of charge. 
 
 

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20.0 
References 
1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 
2007;57(1):43-66. 
2. Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, et al. Cancer Statistics 
Review. National Cancer Institute, Bethesda, MD; 1975-2010 [updated 1975-2010; cited 2011]; 
Available from: http://seer.cancer.gov/csr/1975_2010. 
3. Bluming AZ, Ziegler JL. Regression of Burkitt's lymphoma in association with measles infection. 
Lancet. 1971;2(7715):105-6. 
4. Taqi AM, Abdurrahman MB, Yakubu AM, Fleming AF. Regression of Hodgkin's disease after 
measles. Lancet. 1981;1(8229):1112. 
5. Griffin D, Bellini W. Measles Virus in Fields Virology. Fields B, Knipe D, Howley P, editors: 
Lippincott-Raven Publishers; 1996. 
6. Dorig RE, Marcil A, Chopra A, Richardson CD. The human CD46 molecule is a receptor for measles 
virus (Edmonston strain). Cell. 1993;75(2):295-305. 
7. Muhlebach MD, Mateo M, Sinn PL, Prufer S, Uhlig KM, Leonard VH, et al. Adherens junction 
protein nectin-4 is the epithelial receptor for measles virus. Nature. 2011;480(7378):530-3. PMCID: 
3245798. 
8. Cutts FT, Markowitz LE. Successes and failures in measles control. J Infect Dis. 1994;170 Suppl 
1:S32-41. 
9. Galanis E. Therapeutic potential of oncolytic measles virus: promises and challenges. Clin Pharmacol 
Ther. 2010;88(5):620-5. 
10. Fine PE. Herd immunity: history, theory, practice. Epidemiol Rev. 1993;15(2):265-302. 
11. Peng KW, TenEyck CJ, Galanis E, Kalli KR, Hartmann LC, Russell SJ. Intraperitoneal therapy of 
ovarian cancer using an engineered measles virus. Cancer Res. 2002;62(16):4656-62. 
12. Hasegawa K, Nakamura T, Harvey M, Ikeda Y, Oberg A, Figini M, et al. The use of a tropism-
modified measles virus in folate receptor-targeted virotherapy of ovarian cancer. Clin Cancer Res. 
2006;12(20 Pt 1):6170-8. 
13. Peng KW, Frenzke M, Myers R, Soeffker D, Harvey M, Greiner S, et al. Biodistribution of oncolytic 
measles virus after intraperitoneal administration into Ifnar-CD46Ge transgenic mice. Hum Gene 
Ther. 2003;14(16):1565-77. 
14. Galanis E, Hartmann LC, Cliby WA, Long HJ, Peethambaram PP, Barrette BA, et al. Phase I trial of 
intraperitoneal administration of an oncolytic measles virus strain engineered to express 
carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res. 2010;70(3):875-82. PMCID: 
2890216. 
15. Dingli D, Peng KW, Harvey ME, Greipp PR, O'Connor MK, Cattaneo R, et al. Image-guided 
radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal 
sodium iodide symporter. Blood. 2004;103(5):1641-6. 
16. Galanis E, Atherton PJ, Dowdy SC, Cliby WA, Haluska PJ, Jr., Long HJ. Intraperitoneal (IP) 
administration of an oncolytic measels virus (MV) strain expressing the sodium iodine symporter 
gene in patients (pts) with advanced ovarian cancer (OvCa). Mol Ther. 2013;21(S1):S6. 
17. Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, et al. Phase II study of liposomal 
doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal 
encapsulation. J Clin Oncol. 1997;15(3):987-93. 
18. Ferrandina G, Ludovisi M, Lorusso D, Pignata S, Breda E, Savarese A, et al. Phase III trial of 
gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian 
cancer. J Clin Oncol. 2008;26(6):890-6. 
19. ten Bokkel Huinink W, Lane SR, Ross GA. Long-term survival in a phase III, randomised study of 
topotecan versus paclitaxel in advanced epithelial ovarian carcinoma. Ann Oncol. 2004;15(1):100-3. 

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20. Le T, Hopkins L, Baines KA, Rambout L, Fung-Kee-Fung M. Prospective evaluation of weekly 
topotecan in recurrent platinum-resistant epithelial ovarian cancer. Int J Gynecol Cancer. 
2008;18(3):428-31. 
21. Sehouli J, Stengel D, Harter P, Kurzeder C, Belau A, Bogenrieder T, et al. Topotecan Weekly Versus 
Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized 
multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian 
Cancer Study Group. J Clin Oncol. 2011;29(2):242-8. 
22. Le T, Hopkins L, Baines KA, Rambout L, Al Hayki M, Kee Fung MF. Prospective evaluations of 
continuous weekly paclitaxel regimen in recurrent platinum-resistant epithelial ovarian cancer. 
Gynecol Oncol. 2006;102(1):49-53. 
23. Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, Waggoner S. Phase II trial of weekly 
paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a 
Gynecologic Oncology Group study. Gynecol Oncol. 2006;101(3):436-40. 
24. Myers R, Harvey M, Kaufmann TJ, Greiner SM, Krempski JW, Raffel C, et al. Toxicology study of 
repeat intracerebral administration of a measles virus derivative producing carcinoembryonic antigen 
in rhesus macaques in support of a phase I/II clinical trial for patients with recurrent gliomas. Hum 
Gene Ther. 2008;19(7):690-8. PMCID: 2748764. 
25. Hamburger AW, Dunn FE, White CP. Percoll density gradient separation of cells from human 
malignant effusions. Br J Cancer. 1985;51(2):253-8. PMCID: 1977035. 
26. Kruk PA, Maines-Bandiera SL, Auersperg N. A simplified method to culture human ovarian surface 
epithelium. Lab Invest. 1990;63(1):132-6. 
27. Wu S, Boyer CM, Whitaker RS, Berchuck A, Wiener JR, Weinberg JB, et al. Tumor necrosis factor 
alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor 
cell proliferation and tumor necrosis factor alpha expression. Cancer Res. 1993;53(8):1939-44. 
28. Pocock SJ, Simon R.  Sequential Treatment Assignment with Balancing for Prognostic Factors in the 
Controlled Clinical Trial. Biometrics 31(1):103-115, 1975 Mar. 
29. Therneau TM. How many stratification factors are “too many” to use in a randomization plan? 
Controlled Clin Trials. 1993;14: 98-108. 
30. Rubinstein LV, Kron EL, Freidlin B, Hunsberger S, Ivy SP, Smith MA.  Design issues of randomized 
phase II trials and a proposeal for phase II screening trials.  J Clin Oncol. 2005; 23(28):7199-206. 
31. J Clin Oncol. 2014 May 1;32(13):1302-8. doi: 10.1200/JCO.2013.51.4489. Epub 2014 Mar 17. 
32. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The 
AURELIA open-label randomized phase III trial. 
33. Pujade-Lauraine E1, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, Sorio R, Vergote I, 
Witteveen P, Bamias A, Pereira D, Wimberger P, Oaknin A, Mirza MR, Follana P, Bollag D, Ray-
Coquard I. 
 
 

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Appendix I: ECOG PERFORMANCE STATUS 
 
 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair. 
5 
Dead 
*As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: 
Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649-
655, 1982. 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the 
scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
From 
 
 
 
 
 

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Appendix II: Patient Information Sheet 
 
PATIENT INFORMATION SHEET 
Patient Completed Quality of Life Booklet 
________________________________________________________________________ 
 
You have been given a booklet to complete for this study.  The booklet contains some 
questions about your ‘quality of life’ as a patient receiving treatment for cancer.  Your 
answers will help us to better understand how the treatment you are receiving is affecting 
the way you feel. 
 
1. This booklet contains 1 set of questions:  
a. Functional Assessment of Cancer Therapy – Ovarian (FACT-O) 
 
2. Directions on how to complete the set of questions are written on the top of the  
FACT-O. 
 
3. During your clinic visit:  
a. Please complete the booklet PRIOR TO RECEIVING your next cycle of 
treatment and return it to your nurse or your physician. 
 
4. You will be given your provider’s name and telephone number.  You can call anytime if 
you have any concerns or questions regarding this assessment. 
 
 
Thank you for taking the time to help us. 
 
 

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Appendix III: FACT-O 
FACT-O (Version 4) 
Below is a list of statements that other people with your illness have said are important. 
Please circle or mark one number per line to indicate your response as it applies to 
the past 7 days. 
 
 
PHYSICAL WELL-BEING 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much
GP1 I have a lack of energy …………………...….… 
0 
1 
2 
3 
4 
GP2 I have nausea …………………………………... 
0 
1 
2 
3 
4 
GP3 Because of my physical condition, I have trouble 
meeting the needs of my family .………….. 
0 
1 
2 
3 
4 
GP4 I have pain ……………………………………... 
0 
1 
2 
3 
4 
GP5 I am bothered by side effects of treatment …….. 
0 
1 
2 
3 
4 
GP6 I feel ill ………………………………….…...… 
0 
1 
2 
3 
4 
GP7 I am forced to spend time in bed …….……...…. 
0 
1 
2 
3 
4 
 
 
SOCIAL/FAMILY WELL-BEING 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
GS1 I feel close to my friends…………….…...….… 
0 
1 
2 
3 
4 
GS2 I get emotional support from my family…...…... 
0 
1 
2 
3 
4 
GS3 I get support from my friends………………….. 
0 
1 
2 
3 
4 
GS4 My family has accepted my illness………….…. 
0 
1 
2 
3 
4 
GS5 I am satisfied with family communication about my 
illness………………………………………... 
0 
1 
2 
3 
4 
GS6 I feel close to my partner (or the person who is my 
main support) ………….………………..….. 
0 
1 
2 
3 
4 
Q1 
Regardless of your current level of sexual activity, 
please answer the following question. If you prefer 
not to answer it, please mark this box 
and go to the next section 
0 
1 
2 
3 
4 
GS7 I am satisfied with my sex life …….……...…. 
0 
1 
2 
3 
4 
 
 

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Please circle or mark one number per line to indicate your response as it applies to 
the past 7 days. 
 
EMOTIONAL WELL-BEING 
Not at 
all 
A little 
bit 
Some-
what 
Quite a 
bit 
Very 
much 
 
 
 
 
 
 
 
GE1 I feel sad ……………………..………………….… 
0 
1 
2 
3 
4 
GE2 I am satisified with how I am coping with my illness 
0 
1 
2 
3 
4 
GE3 I am losing hope in the fight against my illness……. 
0 
1 
2 
3 
4 
GE4 I feel nervous ……………………………..………... 
0 
1 
2 
3 
4 
GE5 I worry about dying …………………………….….. 
0 
1 
2 
3 
4 
GE6 I worry that my condition will get worse………...… 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
 
FUNCTIONAL WELL-BEING 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
 
 
 
 
 
 
GF1 I am able to work (include work at home) ……….… 
0 
1 
2 
3 
4 
GF2 My work (include work at home) is fulfilling ……… 
0 
1 
2 
3 
4 
GF3 I am able to enjoy life …………………..……............ 
0 
1 
2 
3 
4 
GF4 I have accepted my illness……………………............ 
0 
1 
2 
3 
4 
GF5 I am sleeping well ……………………….……….….. 
0 
1 
2 
3 
4 
GF6 I am enjoying the things I usually do for fun ..……… 
0 
1 
2 
3 
4 
GF7 I am content with the quality of my life right now….. 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
 
 

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Please circle or mark one number per line to indicate your response as it applies to 
the past 7 days. 
 
ADDITIONAL CONCERNS 
Not at 
all 
A little 
bit 
Some-
what 
Quite 
a bit 
Very 
much 
 
 
 
 
 
 
 
O1 I have swelling in my stomach area…………………. 
0 
1 
2 
3 
4 
C2 I am losing weight…………………………………… 
0 
1 
2 
3 
4 
C3 I have control of my bowels ………………………… 
0 
1 
2 
3 
4 
O2 I have been vomiting………………………...……… 
0 
1 
2 
3 
4 
B5 I am bothered by hair loss ……………….….……… 
0 
1 
2 
3 
4 
C6 I have a good appetite ……………………….……… 
0 
1 
2 
3 
4 
C7 I like the appearance of my body …………………… 
0 
1 
2 
3 
4 
BMT5 I am able to get around by myself……………...…… 
0 
1 
2 
3 
4 
B9 I am able to feel like a woman………………….…… 
0 
1 
2 
3 
4 
O3 I have cramps in my stomach area…………….….… 
0 
1 
2 
3 
4 
BL4 I am interested in sex ..…………..………….….…… 
0 
1 
2 
3 
4 
BMT7 I have concerns about my ability to have children…. 
0 
1 
2 
3 
4 
 
 
 
 
 
 
 
 
 

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Appendix IV: Prep and Storage of MV-NIS 
 
Standard Operating Procedure for the Preparation of MV-NIS (NIS-Measles Virus-Edmonston 
Strain) dilutions for patient administration 
 
 
MV-NIS will be manufactured at the Mayo Clinic Viral Vector Production Laboratory of the 
Department of Molecular Medicine.  The product will be labeled appropriately and provided to 
the designated pharmacy in single-dose vials with batch-dependant infectious titer expressed 
inTCID50 units/mL. 
 
MV-NIS containing vials will be transported on dry ice and stored at ≤-65° C. 
 
The appropriate number of vials will be thawed and diluted in a timely manner to provide 
product ready for patient administration. 
 
The appropriate amount of MV-NIS will be withdrawn from the vial(s). Several dilution steps 
may be necessary to accurately compound the doses per clinical protocol. This will be 
accomplished by diluting MV-NIS in preservative-free normal saline to a total volume of 500 
mL in an infusion bag for intraperitoneal administration.  MAYO ONLY: Any remaining thawed 
virus or intermediate dilutions will be refrigerated and transported on ice to Mayo Clinic Viral 
Vector Production Laboratory for determination of TCID 50/mL as indicated. 
 
All reconstitution and preparation will be performed by the Pharmacy in a Biological Safety 
Cabinet using aseptic technique. 
 
The expiration of the diluted virus is 2.5 hours at room temperature after preparation of the 
infusion bag is complete. 
 
The final product for administration will be labeled appropriately for dispensing within the 
institution. 
 
 
 

MC1365 
75 
Amendment 8 
Protocol Version Date: 06Aug2020 
Appendix V: Arm Assignment Script for Bulky Disease 
 
Arm A: Bulky Disease 
The patient is randomized to Arm A. Please 
place an intraperitoneal port prior to 
surgical closure. 
 
Arm B: Bulky Disease 
The patient is randomized to Arm B. Please 
DO NOT place an intraperitoneal port; rather 
proceed with surgical closure.