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 III Fallopian Tube Cancer, Stage III Ovarian Cancer, Stage III Primary Peritoneal Cancer, Stage IV Fallopian Tube Cancer, Stage IV Ovarian Cancer, Stage IV Primary Peritoneal Cancer
Conditions
Brief summary
This phase II trial studies how well pUMVC3-IGFBP2 plasmid deoxyribonucleic acid (DNA) vaccine (IGFBP-2 vaccine) and combination chemotherapy work in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer undergoing surgery. IGFBP-2 is a protein found in the blood and tumor cells of most who have been diagnosed with ovarian cancer. Too much IGFBP-2 has been associated with more invasive disease. Vaccines made from DNA may help the body build an effective immune response to kill tumor cells that express IGFBP-2. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving IGFBP-2 vaccine and combination chemotherapy may work better in treating patients with stage III-IV ovarian, fallopian tube, or primary peritoneal cancer undergoing surgery.
Detailed description
PRIMARY OBJECTIVES: I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases the rate of complete pathologic response (CR). SECONDARY OBJECTIVES: I. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy increases progression free survival at 12 months. II. Determine whether the addition of an IGFBP-2 vaccine to neoadjuvant chemotherapy improves overall survival. III. To determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of tumor infiltrating lymphocytes (TIL) in the tumor. IV. To assess the level of IGFBP-2 type 1 helper cells (Th1) elicited with vaccination concurrent with chemotherapy. EXPLORATORY OBJECTIVES: I. To explore whether there is a predictive genomic signature for CR induction when IGFBP-2 vaccination is used in combination with chemotherapy. OUTLINE: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine intradermally (ID) 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery. After completion of study treatment, patients are followed up at 6 months and then once a year for 5 years.
Interventions
DRUGCarboplatin
Given IV
PROCEDUREGynecological Surgical Procedure
Undergo cytoreductive surgery
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPaclitaxel
Given IV
Given ID
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with newly diagnosed advanced stage (III/IV) ovarian cancer (ovarian/fallopian tube/peritoneal cancer) who have been recommended to receive neoadjuvant carboplatin/paclitaxel chemotherapy with subsequent cytoreductive surgery * Patients must have Eastern Cooperative Oncology Group (ECOG) performance status score of =\< 2 * Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment * Estimated life expectancy of more than 6 months * White blood cells (WBC) \>= 3000/mm\^3 within 30 days of enrollment to study * Hemoglobin (Hgb) \>= 10 g/dl within 30 days of enrollment to study * Hematocrit (Hct) \>= 28% within 30 days of enrollment to study * Serum creatinine =\< 2.0 mg/dl or creatinine clearance \> 60 ml/min within 30 days of enrollment to study * Total bilirubin =\< 2.5 mg/dl within 30 days of enrollment to study * Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =\< 3 times upper limit of normal (ULN) within 30 days of enrollment to study * Blood glucose \<1.5 ULN within 30 days of enrollment to study * All patients who are having sex that can lead to pregnancy must agree to contraception for the duration of the study * Patients must be at least 18 years of age
Exclusion criteria
* Patients with any of the following cardiac conditions: * Symptomatic restrictive cardiomyopathy * Unstable angina within 4 months prior to enrollment * New York Heart Association functional class III-IV heart failure on active treatment * Symptomatic pericardial effusion * Uncontrolled diabetes * History of (non-infectious) pneumonitis that required steroids or current pneumonitis * Patients with any contraindication to receiving rhuGM-CSF based products * Patients with any clinically significant autoimmune disease uncontrolled with treatment * Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of their treatment regimen * Patients who are simultaneously enrolled in any other treatment study * Patients who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Pathologic Complete Response (CR) | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) | The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27 | At the time of cytoreductive surgery | Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes. |
| Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay | Up to 6 months after last vaccine | Will be correlated to tumor burden at definitive surgery. |
| Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) | Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL. |
| Progression Free Survival (PFS) | Up to 12 months | Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test. |
| Tumor Burden | At the time of cytoreductive surgery | Will be correlated to level of IGFBP-2 Th1 cells. |
| Overall Survival (OS) | Up to 5 years | Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors | At the time of cytoreductive surgery | Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy, IGFBP-2 Vaccine) Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour followed by IGFBP-2 vaccine ID 2 weeks later. Treatment repeats every 3 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of 3 cycles, patients then undergo cytoreductive surgery.
Carboplatin: Given IV
Gynecological Surgical Procedure: Undergo cytoreductive surgery
Laboratory Biomarker Analysis: Correlative studies
Paclitaxel: Given IV
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine: Given ID | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy, IGFBP-2 Vaccine) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 64 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Rate of Pathologic Complete Response (CR)
The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells).
Time frame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
Population: Review of the pathology report from cytoreductive surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Rate of Pathologic Complete Response (CR) | 0 Participants |
Secondary
Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27
Will be performed and quantitated using published methods and will be correlated with surgical CR by the Man-Whitney U or one-way analysis of variance test depending on the distribution of TIL outcomes.
Time frame: At the time of cytoreductive surgery
Population: Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.
Secondary
Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay
Will be correlated to tumor burden at definitive surgery.
Time frame: Up to 6 months after last vaccine
Population: Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.
Secondary
Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor
Will be assessed by immunohistochemistry (IHC) to determine whether IGFBP-2 vaccination in combination with chemotherapy increases the level of TIL in the tumor. This was done by assessing the level of IGFBP-2 Th1 elicited by study treatment (vaccination concurrent with chemotherapy). we are looking for an increase in TIL.
Time frame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
Population: Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.
Secondary
Overall Survival (OS)
Will be compared between the treatment arms. Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median OS of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.
Time frame: Up to 5 years
Population: Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Overall Survival (OS) | Deceased - passed away after they left the study | 3 Participants |
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Overall Survival (OS) | Alive | 6 Participants |
Secondary
Progression Free Survival (PFS)
Large differences in PFS if observed between the treatment groups will be noted and described. Will be plotted by Kaplan-Meier curve, and compared to the survival data reported by Vergote et al which reported median PFS of 12 months and median overall survival (OS) of 30 months for patients treated with neoadjuvant chemotherapy by a log-rank test.
Time frame: Up to 12 months
Population: Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Progression Free Survival (PFS) | PFS | 2 Participants |
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Progression Free Survival (PFS) | Recurrence | 2 Participants |
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Progression Free Survival (PFS) | Deceased - passed away after they left the study | 3 Participants |
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Progression Free Survival (PFS) | Status unchanged | 2 Participants |
Secondary
Tumor Burden
Will be correlated to level of IGFBP-2 Th1 cells.
Time frame: At the time of cytoreductive surgery
Population: Target enrollment was not met. The study was terminated. Planned statistical analysis was not performed due to termination of study, lack of funding, and insufficient enrollment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Tumor Burden | Debulking surgery | 7 Participants |
| Treatment (Chemotherapy, IGFBP-2 Vaccine) | Tumor Burden | Not evaluable | 2 Participants |
Other Pre-specified
Predictive Signature of CR Induction When Vaccinated With an IGFBP-2 Vaccine in Combination With Neoadjuvant Chemotherapy Assessed by Whole Exome Sequencing on Vaccinated Patients' Tumors
Will use the LASSO regularized regression method to generate preliminary data for a predictive signature. Will correlate mutational profiles with primary platinum sensitive, resistance and refractory outcomes, leveraging the Cancer Genome Atlas data publicly available, to determine differences induced by vaccination.
Time frame: At the time of cytoreductive surgery
Population: Target enrollment was not met. Samples were collected but planned laboratory/statistical analyses were not performed due to termination of study, lack of funding, and insufficient enrollment.