Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Digestive System Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pathologic Complete Response

Carcinoma

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Vaccines

Tubulin Modulators

Antimitotic Agents

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.

Gynecological Surgical Procedure

Laboratory Biomarker Analysis

pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine

John Liao

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.

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.

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

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

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.

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).

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.

Will be correlated to tumor burden at definitive surgery.

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.

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.

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.

Will be correlated to level of IGFBP-2 Th1 cells.

National Cancer Institute (NCI)

University of Washington

Professor, Department of Medicine, Division of Oncology

We used CTCAE v4.0 for this study. The adverse events reported here include all events regardless of whether they were unrelated and related to study treatment). Please note that these tables record every adverse event for every subject regardless of severity. For example, a subject may have an injection site reaction at each of the three vaccines where another may not. Each one of these injection site reactions is recorded for that one subject.

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

Treatment (Chemotherapy, IGFBP-2 Vaccine)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

11 participants signed consent 9 participants received treatment 9 participants completed all 3 vaccines and 1 month follow-up

Director of Clinical Operations

Review of the pathology report from cytoreductive surgery.

Rate of Pathologic Complete Response (CR)

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.

Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27

Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay

Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor

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.

Overall Survival (OS)

Progression Free Survival (PFS)

Tumor Burden

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

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery	NCT03029611	Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... Stage IIIB Fall... Stage IIIB Ovar... Stage IIIB Prim... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar...	Carboplatin Gynecological S... Laboratory Biom... Paclitaxel pUMVC3-hIGFBP-2...	18 Years -	University of Washington
IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery	NCT03029611	Stage III Fallo... Stage III Ovari... Stage III Prima... Stage IIIA Fall... Stage IIIA Ovar... Stage IIIA Prim... Stage IIIB Fall... Stage IIIB Ovar... Stage IIIB Prim... Stage IIIC Fall... Stage IIIC Ovar... Stage IIIC Prim... Stage IV Fallop... Stage IV Ovaria... Stage IV Primar...	Carboplatin Gynecological S... Laboratory Biom... Paclitaxel pUMVC3-hIGFBP-2...	18 Years -	University of Washington

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