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

University of Washington

Status and phase: Terminated; Phase 2

Conditions: Stage IV Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage III Primary Peritoneal Cancer; Stage IIIC Primary Peritoneal Cancer; Stage III Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IV Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Fallopian Tube Cancer

Treatments: Drug: Paclitaxel; Biological: pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine; Procedure: Gynecological Surgical Procedure; Drug: Carboplatin; Other: Laboratory Biomarker Analysis

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03029611

NCI-2017-00034 (Registry Identifier)

9760

RG1717017 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 1 patient group

Treatment (chemotherapy, IGFBP-2 vaccine)

Experimental group

Description:

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.

Treatment:

Biological: pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine

Other: Laboratory Biomarker Analysis

Procedure: Gynecological Surgical Procedure

Drug: Carboplatin

Drug: Paclitaxel