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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2017-00034 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| RG1717017 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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Terminated due to lack of funding
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemotherapy, IGFBP-2 vaccine) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Given IV |
|
| 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.) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. |
Inclusion Criteria:
Exclusion Criteria:
Patients with any of the following cardiac conditions:
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
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| Name | Affiliation | Role |
|---|---|---|
| John Liao | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutch/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Chemotherapy, IGFBP-2 Vaccine) | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 22, 2020 |
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| Gynecological Surgical Procedure | Procedure | Undergo cytoreductive surgery |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Paclitaxel | Drug | Given IV |
|
|
| pUMVC3-hIGFBP-2 Multi-Epitope Plasmid DNA Vaccine | Biological | Given ID |
|
| 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 |
| At the time of cytoreductive surgery |
| COMPLETED |
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| NOT COMPLETED |
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11 participants signed consent 9 participants received treatment 9 participants completed all 3 vaccines and 1 month follow-up
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Chemotherapy, IGFBP-2 Vaccine) | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Review of the pathology report from cytoreductive surgery. | Posted | Count of Participants | Participants | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) |
|
|
| ||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | At the time of cytoreductive surgery |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Up to 6 months after last vaccine |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.) |
|
| |||||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | Up to 5 years |
|
| |||||||||||||||||||||||||||
| Secondary | 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. | 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. | Posted | Count of Participants | Participants | Up to 12 months |
|
| |||||||||||||||||||||||||||
| Secondary | Tumor Burden | Will be correlated to level of IGFBP-2 Th1 cells. | 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. | Posted | Count of Participants | Participants | At the time of cytoreductive surgery |
|
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| Other Pre-specified | 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 | 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. | 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. | Posted | At the time of cytoreductive surgery |
|
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The Adverse Events were collected after first vaccination and through to 6 months post vaccination.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Chemotherapy, IGFBP-2 Vaccine) | 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 | 3 | 9 | 0 | 9 | 9 | 9 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| White blood cell decreased | Investigations | Non-systematic Assessment |
| ||
| Platelet count decreased | Investigations | Non-systematic Assessment | Unrelated to study treatment |
| |
| Weight loss | Investigations | Non-systematic Assessment | Unrelated to study treatment |
| |
| Creatinine increased | Investigations | Non-systematic Assessment | Unrelated to study treatment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Unrelated to study treatment |
| |
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment | 4 of 6 events are unrelated to study treatment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Other - leg weakness | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Other - "pulled muscle" in left upper quadrant | Musculoskeletal and connective tissue disorders | Non-systematic Assessment | Unrelated to study treatment |
| |
| Urinary tract infection | Infections and infestations | Non-systematic Assessment | 1 of 2 events is unrelated to study treatment |
| |
| Other Infection | Infections and infestations | Non-systematic Assessment | Unrelated to study treatment |
| |
| Wound infection | Infections and infestations | Non-systematic Assessment | Unrelated to study treatment |
| |
| Palpitations | Cardiac disorders | Non-systematic Assessment | 1 of 2 events is unrelated to study treatment |
| |
| Cognitive disturbance | Nervous system disorders | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment | 1 of 3 events is unrelated to the study treatment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment | Unrelated to study treatment |
| |
| Nausea | Gastrointestinal disorders | Non-systematic Assessment | 1 of 3 events is unrelated to the study treatment |
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| Vomiting | Gastrointestinal disorders | Non-systematic Assessment | 1 of 3 events is unrelated to the study treatment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment | 2 of 5 events are unrelated to the study treatment |
| |
| Abdominal distension | Gastrointestinal disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment | Unrelated to study treatment |
| |
| Ascites | Gastrointestinal disorders | Non-systematic Assessment | Unrelated to study treatment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Alopecia | Skin and subcutaneous tissue disorders | Non-systematic Assessment | 1 of 12 events are unrelated to the study treatment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Edema limbs | General disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Non-cardiac chest pain | General disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Pain | General disorders | Non-systematic Assessment | 5 of 6 events are unrelated to the study drug |
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| Injection site reaction | General disorders | Non-systematic Assessment |
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| Flushing | Vascular disorders | Non-systematic Assessment |
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| Hypotension | Vascular disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Hypoalbuminemia | Metabolism and nutrition disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Cystitis noninfective | Renal and urinary disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Hematuria | Renal and urinary disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Acute kidney injury | Renal and urinary disorders | Non-systematic Assessment | Unrelated to study treatment |
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| Other - paracentisis | Surgical and medical procedures | Non-systematic Assessment | Unrelated to study treatment |
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| Other - IVC filter placed due to clots | Surgical and medical procedures | Non-systematic Assessment | Unrelated to study treatment |
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| Other - thoracentesis x 2 due to pleural effusion. Hospitalized | Surgical and medical procedures | Non-systematic Assessment | Unrelated to study treatment |
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| Other - ex-lap, RSO, omentectomy, appendectomy, tumor debulking | Surgical and medical procedures | Non-systematic Assessment | Unrelated to study treatment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Operations | UWashington (University of Washington) | 206-616-2305 | childj@u.washington.edu |
| Sep 16, 2021 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 22, 2020 | Sep 16, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D005185 | Fallopian Tube Neoplasms |
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005184 | Fallopian Tube Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D013509 | Gynecologic Surgical Procedures |
| D017239 | Paclitaxel |
| D013660 | Taxes |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D013519 | Urogenital Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D004467 | Economics |
| D004472 | Health Care Economics and Organizations |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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