Stage IA Fallopian Tube Cancer, Stage IA Ovarian Cancer, Stage IB Fallopian Tube Cancer, Stage IB Ovarian Cancer, Stage IC Fallopian Tube Cancer, Stage IC Ovarian Cancer, Stage IIA Fallopian Tube Cancer, Stage IIA Ovarian Cancer, Stage IIB Fallopian Tube Cancer, Stage IIB Ovarian Cancer, Stage IIC Fallopian Tube Cancer, Stage IIC Ovarian Cancer, Stage IIIA Fallopian Tube Cancer, Stage IIIA Ovarian Cancer, Stage IIIA Primary Peritoneal Cancer, Stage IIIB Fallopian Tube Cancer, Stage IIIB Ovarian Cancer, Stage IIIB Primary Peritoneal Cancer, Stage IIIC Fallopian Tube Cancer, Stage IIIC Ovarian Cancer, Stage IIIC Primary Peritoneal Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Cancer, Stage IV Primary Peritoneal Cancer
Conditions
Brief summary
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.
Detailed description
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPolyvalent Antigen-KLH Conjugate Vaccine
Given SC
BIOLOGICALSaponin-based Immunoadjuvant OBI-821
Given SC
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Every 3 month until 2 years from start of treatment, then every 6 months for 3 years; then annually if patient remains in remission. | Progression-free survival is the period of time from the date of randomization to the date of first clinical, biochemical, or radiological evidence of progression, death due to any cause or date of last contact, whichever occurs first. Progression is defined as increasing clinical, radiological or histological evidence of disease. Patients with progressing disease based on clinical or histologic basis (ie. biopsy) must also have CT scan of the abdomen and pelvis performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | During treatment period and up to 30 days after stopping the study treatment; up to 83 weeks. | Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0. |
| Overall Survival | From study entry to death or last contact, up to 5 years of follow-up. | Overall survival is defined as the duration of time from study entry to time of death due to any cause or the date of last contact. |
Countries
United States
Participant flow
Recruitment details
The study was activated on 7/26/2010 and closed to accrual on 2/4/2013.
Participants by arm
| Arm | Count |
|---|---|
| Polyvalent Antigen-KLH+OPT-821 Vaccine Polyvalent antigen-KLH + OPT-821 vaccine subcutaneously administered on weeks 1, 2, 3, 7, 11, 23, 35, 47, 59, 71 and 83 for a total of 11 vaccines until disease progression or adverse effects prohibit further treatment. 1 cycle = 1 vaccine | 86 |
| Non-specific Immunity With OPT-821 Non-specific OPT-821 subcutaneously administered on weeks 1, 2, 3, 7, 11, 23, 35, 47, 59, 71 and 83 for a total of 11 vaccines until disease progression or adverse effects prohibit further treatment. 1 cycle = 1 vaccine | 85 |
| Total | 171 |
Baseline characteristics
| Characteristic | Polyvalent Antigen-KLH+OPT-821 Vaccine | Non-specific Immunity With OPT-821 | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 8.6 | 59.1 years STANDARD_DEVIATION 9.1 | 60.2 years STANDARD_DEVIATION 8.9 |
| Age, Customized 40-49 | 8 Participants | 14 Participants | 22 Participants |
| Age, Customized 50-59 | 29 Participants | 31 Participants | 60 Participants |
| Age, Customized 60-69 | 37 Participants | 26 Participants | 63 Participants |
| Age, Customized 70-79 | 10 Participants | 14 Participants | 24 Participants |
| Age, Customized 80-89 | 2 Participants | 0 Participants | 2 Participants |
| Cell Type Adenocarcinoma, Unsp. | 3 Participants | 1 Participants | 4 Participants |
| Cell Type Adenocarcinoma with Squam. Diff ' n | 0 Participants | 1 Participants | 1 Participants |
| Cell Type Adenosquamous | 2 Participants | 0 Participants | 2 Participants |
| Cell Type Clear Cell Carcinoma | 1 Participants | 1 Participants | 2 Participants |
| Cell Type Endometrioid Adenocarcinoma | 6 Participants | 1 Participants | 7 Participants |
| Cell Type Mixed Epithelial Carcinoma | 2 Participants | 2 Participants | 4 Participants |
| Cell Type Other Carcinoma | 2 Participants | 0 Participants | 2 Participants |
| Cell Type Serous Adenocarcinoma | 69 Participants | 76 Participants | 145 Participants |
| Cell Type Transitional Cell Carcinoma | 0 Participants | 2 Participants | 2 Participants |
| Cell Type Undifferentiated Carcinoma | 1 Participants | 1 Participants | 2 Participants |
| Recurring and/or Persistent Disease | 86 Participants | 85 Participants | 171 Participants |
| Sex: Female, Male Female | 86 Participants | 85 Participants | 171 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 86 | 82 / 84 |
| serious Total, serious adverse events | 5 / 86 | 14 / 84 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival is the period of time from the date of randomization to the date of first clinical, biochemical, or radiological evidence of progression, death due to any cause or date of last contact, whichever occurs first. Progression is defined as increasing clinical, radiological or histological evidence of disease. Patients with progressing disease based on clinical or histologic basis (ie. biopsy) must also have CT scan of the abdomen and pelvis performed.
Time frame: Every 3 month until 2 years from start of treatment, then every 6 months for 3 years; then annually if patient remains in remission.
Population: Enrolled and randomized participants. 95% two-sided confidence interval
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Progression-free Survival (PFS) | 5.9 Months |
| Non-specific Immunity With OPT-821 | Progression-free Survival (PFS) | 6.5 Months |
Secondary
Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Time frame: During treatment period and up to 30 days after stopping the study treatment; up to 83 weeks.
Population: Enrolled and randomized and treated Patients. Grade 3 or worse adverse events for gastrointestinal disorders were significantly associated with treatment arm at significant level of 0.05 by two-sided Fisher's exact test. The reporting arm 2 had higher proportion of patients with reported grade 3 or worse adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Renal and urinary disorders | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Eye disorders | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Nervous System | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Vascular disorders | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Other Investigations | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Leukopenia | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Thrombocytopenia | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Neutropenia | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Anemia | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Gastrointestinal Disorders | 2 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | General disorders & administration site condition | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Immune system disorders | 0 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Infections and infestations | 1 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Metabolism and nutrition disorders | 3 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Neoplasms benign, malignant & unspecified | 2 participants |
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Psychiatric disorders | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Metabolism and nutrition disorders | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Gastrointestinal Disorders | 10 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Eye disorders | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Psychiatric disorders | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Renal and urinary disorders | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | General disorders & administration site condition | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Vascular disorders | 2 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Anemia | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Neoplasms benign, malignant & unspecified | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Immune system disorders | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Leukopenia | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Nervous System | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Thrombocytopenia | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Infections and infestations | 0 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Neutropenia | 1 participants |
| Non-specific Immunity With OPT-821 | Incidence of Adverse Effects (Grade 3 or Higher) During Treatment Period | Other Investigations | 0 participants |
Secondary
Overall Survival
Overall survival is defined as the duration of time from study entry to time of death due to any cause or the date of last contact.
Time frame: From study entry to death or last contact, up to 5 years of follow-up.
Population: Enrolled and randomized participants. The upper limit of the 95% confidence interval for OS median in arm 1 is not available because the data is not mature enough for estimation at the time of this report.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Polyvalent Antigen-KLH+OPT-821 Vaccine | Overall Survival | 46.5 Months |
| Non-specific Immunity With OPT-821 | Overall Survival | 46.2 Months |