Clinical trial NCT03029611: IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-01-24
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of Pathologic Complete Response (CR)
timeFrame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
Secondary outcomes:
measure: Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27
timeFrame: At the time of cytoreductive surgery
measure: Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay
timeFrame: Up to 6 months after last vaccine
measure: Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor
timeFrame: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Tumor Burden
timeFrame: At the time of cytoreductive surgery
Other outcomes:
measure: 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
timeFrame: At the time of cytoreductive surgery
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: John Liao
role: PRINCIPAL_INVESTIGATOR
References: