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

Primary Purpose

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

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carboplatin
Gynecological Surgical Procedure
Laboratory Biomarker Analysis
Paclitaxel
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Fallopian Tube Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy, IGFBP-2 vaccine)

Arm 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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Full Information

First Posted
January 10, 2017
Last Updated
December 17, 2021
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03029611
Brief Title
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

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Terminated due to lack of funding
Study Start Date
April 3, 2017 (Actual)
Primary Completion Date
October 17, 2018 (Actual)
Study Completion Date
December 10, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy, IGFBP-2 vaccine)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Gynecological Surgical Procedure
Other Intervention Name(s)
gynecologic surgery, Gynecologic Surgical Procedure, gynecologic surgical procedures, gynecological surgery
Intervention Description
Undergo cytoreductive surgery
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine
Intervention Description
Given ID
Primary Outcome Measure Information:
Title
Rate of Pathologic Complete Response (CR)
Description
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.)
Secondary Outcome Measure Information:
Title
Immunohistochemistry (IHC) Staining for CD3, CD4, CD8, and CD27
Description
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
Title
Level of IGFBP-2 Th1 Cells Elicited With Vaccine Assessed by Enzyme-linked Immunosorbent Spot Assay
Description
Will be correlated to tumor burden at definitive surgery.
Time Frame
Up to 6 months after last vaccine
Title
Level of Tumor Infiltrating Lymphocytes (TIL) in Tumor
Description
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.)
Title
Overall Survival (OS)
Description
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
Title
Progression Free Survival (PFS)
Description
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
Title
Tumor Burden
Description
Will be correlated to level of IGFBP-2 Th1 cells.
Time Frame
At the time of cytoreductive surgery
Other Pre-specified Outcome Measures:
Title
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
Description
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Liao
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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