Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

PRIMARY OBJECTIVES:

I. Determine the safety of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine with sirolimus at varying
dose and schedule.

SECONDARY OBJECTIVES:

I. To determine the effectiveness of sirolimus on enhancing vaccine efficacy by assessing
NY-ESO-1 specific cellular and humoral immunity: peripheral blood NY-ESO-1 specific cluster
of differentiation (CD)8+ and CD4+ T-cells; peripheral blood NY-ESO-1 specific antibodies;
peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T-cells.

II. Explore time to disease progression.

OUTLINE: This is a dose-escalation study of sirolimus.

Patients receive ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine subcutaneously (SC) on day 1 and
sargramostim (GM-CSF) SC on days 1-4. Patients also receive sirolimus orally (PO) once daily
(QD) on days 1-14 OR 15-28 OR 1-28. Treatment repeats every 28 days for up to 4 courses in
the absence of disease progression or unacceptable toxicity. Patients then receive an
additional course of ALVAC(2)-NY-ESO-1 (M)/TRICOM vaccine only followed by ALVAC(2)-NY-ESO-I
(M)/TRICOM vaccine SC 8 weeks after completion of course 4.

After completion of study treatment, patients are followed up at 30 days, and 6 and 12
months.

Inclusion Criteria:

- Eligible patients will be women with stages II-IV epithelial ovarian, fallopian tube,
or primary peritoneal carcinoma who have completed standard therapy for primary or
recurrent disease (i.e., patients who would normally be observed); eligible patients
may have asymptomatic residual measurable disease on physical examination and/or
computed tomography (CT) scan, and/or may have an elevated cancer antigen 125
(CA-125); or may be in complete clinical remission after treatment for primary or
recurrent disease; these patients would normally enter a period of observation after
standard management

- Any human leukocyte antigen (HLA) type; (historic HLA typing is permitted)

- Tumor expression of NY-ESO-1 or cancer/testis antigen 2 (LAGE-1) by
immunohistochemistry (IHC) and/or real-time polymerase chain reaction (RT-PCR)

- No allergy to eggs

- Life expectancy > 6 months

- Hematology and biochemistry laboratory results within the limits normally expected for
the patient population, without evidence of major organ failure

- Absolute neutrophil count (ANC) >= 1,000/uL

- Platelet >= 75,000/uL

- Hemoglobin (Hgb) >= 8 g/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or
serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) =< 3 x ULN

- Serum creatinine =< 2 x ULN

- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5

- Electrocardiogram, showing no evidence of congestive heart failure, myocardial
infarction, and cardiomyopathy

- Have been informed of other treatment options

- Patient or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2

- Demonstrate the ability to swallow and retain oral medication

- Patients of child-bearing potential must agree to use acceptable contraceptive methods
(e.g., double barrier) during treatment

- Patients may have received previous NY-ESO-1 vaccine therapy

Exclusion Criteria:

- Metastatic disease to the central nervous system for which other therapeutic options,
including radiotherapy, may be available

- Other serious illnesses (e.g. serious infections requiring antibiotics, bleeding
disorders)

- History of severe autoimmune disorders requiring use of steroids or other
immunosuppressives

- Concomitant systemic treatment with corticosteroids, anti-histamine or nonsteroidal
anti-inflammatory drugs and other platelet inhibitory agents, strong
inhibitors/inducers of cytochrome P450, family 3, subfamily A, polypeptide 4
(CYP450-3A4)

- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing
of study drug (6 weeks for nitrosoureas); concomitant hormonal therapies for breast
cancers are allowed

- Known allergy or history of life threatening reaction to GM-CSF

- Clinically significant heart disease (N-YHA Class III or IV)

- Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to first dosing of study drug

- Known hepatitis B, hepatitis C, or HIV

- Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study

- Lack of availability of a patient for immunological and clinical follow-up assessment

- Known pulmonary hypertension

- Known hypersensitivity to sirolimus

- Evidence of current drug or alcohol abuse or psychiatric impairment, which in the
investigator's opinion will prevent completion of the protocol therapy or follow-up

- Pregnant or nursing female patients

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the patient an unsuitable
candidate to receive study drug; (i.e., any significant medical illness or abnormal
laboratory finding that would, in the investigator's judgment, increase the subject's
risk by participating in this study)