IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study of Concurrent IGFBP-2 Vaccination and Neoadjuvant Chemotherapy to Increase the Rate of Pathologic Complete Response at the Time of Cytoreductive Surgery

Conditions
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Stage III Fallopian Tube Cancer, Stage III Ovarian Cancer, Stage III Primary Peritoneal 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

Intervention / Treatment
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* Drug: Carboplatin
* Procedure: Gynecological Surgical Procedure
* Other: Laboratory Biomarker Analysis
* Drug: Paclitaxel
* Biological: pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy, IGFBP-2 vaccine)<br>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. | Drug: Carboplatin<br>* Given IV<br>* Other names: Ribocarbo;Procedure: Gynecological Surgical Procedure<br>* Undergo cytoreductive surgery<br>* Other names: gynecological surgery;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol Konzentrat;Biological: pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine<br>* Given ID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At the time of cytoreductive surgery | 
| 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. | Up to 6 months after last vaccine | 
| 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. | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) | 
| 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. | Up to 5 years | 
| 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. | Up to 12 months | 
| Tumor Burden | Will be correlated to level of IGFBP-2 Th1 cells. | At the time of cytoreductive surgery |