This randomized phase II trial studies OPT-821 and vaccine therapy to see how well they work compared with OPT-821 alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer that has decreased or disappeared, but the cancer may still be in the body. Biological therapies, such as OPT-821, may stimulate the immune system in different ways and stop tumor cells from growing. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether OPT-821 is more effective with or without vaccine therapy in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer.

PRIMARY OBJECTIVES:

I. To determine if a polyvalent vaccine (including GM2-keyhole limpet hemocyanin [KLH], Globo-H-KLH, Tn-mucin 1 [MUC1]-32mer-KLH, and Thompson Friedreich antigen [TF]-KLH plus OPT-821) decreases the hazard of progression or death compared to a vaccine containing OPT-821 alone in women with epithelial ovarian, fallopian tube, or peritoneal cancer in second or third complete clinical remission.

SECONDARY OBJECTIVES:

I. To compare the treatment arms with respect to the incidence of toxicities. II. To determine if the polyvalent vaccine decreases the hazard of death compared to a vaccine containing OPT-821 alone in women with epithelial ovarian, fallopian tube, or peritoneal cancer in second or third complete clinical remission.

TERTIARY OBJECTIVES:

I. To evaluate the immune response (by enzyme linked immunosorbent assay [ELISA]) in participants, in order to determine if the outcome correlates with antigen-specific immune titers.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive polyvalent antigen-KLH conjugate vaccine and immunological adjuvant OPT-821 subcutaneously (SC) once in weeks 1, 2, 3, 7, 11, 23, 35, 47, 59, 71, and 83 in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive immunological adjuvant OPT-821 SC as in Arm I.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Inclusion Criteria:

• Patients with histologically documented epithelial carcinoma arising in the ovary, fallopian tube, or peritoneum, of any stage or grade at diagnosis; all patients must have had cytoreductive surgery and chemotherapy with at least one platinum-based chemotherapy regimen as part of primary treatment
• Patients who recurred on or after initial therapy, and are now in a second or third complete clinical remission and who are within four months of their last treatment are eligible; complete clinical remission is defined as serum cancer antigen (CA)-125 within institutional normal limits, negative physical examination, and no definite evidence of disease by computed tomography (CT) of the abdomen and pelvis; lymph nodes and/or soft tissue abnormalities =< 1.0 cm are often present in the pelvis and will not be considered definite evidence of disease; eligibility is determined by anatomical imaging only (ie. magnetic resonance imaging [MRI] or CT); a positive positron emission tomography (PET) image (if performed) will not exclude a patient if other criteria are met and anatomical imaging is negative
• Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3, equivalent to Common Toxicity Criteria for Adverse Events (CTCAE version [v]4.0) grade 1
• Platelets greater than or equal to 100,000/mm^3
• Serum creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE v4.0 grade 1
• Bilirubin less than or equal to 2.5 x ULN
• Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminse (SGPT) less than or equal to 2.5 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Patients must have a Gynecological Oncology Group (GOG) performance status of 0, 1, or 2
• Patients who have signed the informed consent document and signed the authorization permitting release of personal health information
• Patients of childbearing potential must have a negative serum pregnancy test prior to study entry and must be practicing an effective form of birth control; nursing mothers are excluded

Exclusion Criteria:

• With the exception of non-melanoma skin cancer, patients with other invasive malignancies who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy are excluded
• Patients whose circumstances at the time of entry onto the protocol would not permit completion of study or required follow up
• Patients who have an allergy to shellfish