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出境医 / 临床实验 / Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients

Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients

Study Description
Brief Summary:
This study tests the hypothesis that IV iron sucrose infusions given to iron deficient ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and decrease transfusion of packed red blood cells in the peri-operative period. 21 participants at least 18 years of age with epithelial ovarian cancer of any stage requiring neoadjuvant chemotherapy and surgery will be enrolled. Participants will be on study for a period of up to 3 months.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Anemia Iron Deficiency Anemia Other: Iron Sucrose Phase 1 Phase 2

Detailed Description:

Iron deficiency and anemia are common in cancer patients. Data from the University of Wisconsin (UW) suggest that more than 50% of ovarian cancer patients undergo blood transfusion during their cancer treatments. Transfusion rates are particularly high in patients who receive neoadjuvant chemotherapy (NACT), despite multiple opportunities to diagnose and treat anemia prior to surgery. Blood transfusions have been associated with worse survival in ovarian cancer patients. Seventy-seven percent of ovarian cancer patients who receive NACT at the UW are anemic prior to surgery, and the same percentage receive a perioperative blood transfusion, defined as a blood transfusion within 72 hours of surgery. Iron deficiency without anemia is also common in cancer patients, though little has been published regarding how frequently it occurs in ovarian cancer patients. Functional iron deficiency, a lack of iron incorporation into erythroid precursors despite adequate iron stores, is also common in cancer patients. Study investigators hypothesize that IV iron sucrose infusions given to iron deficient ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and decrease transfusion of packed red blood cells in the peri-operative period.

Eligible participants will have a new epithelial ovarian cancer diagnosis, with planned neoadjuvant chemotherapy and interval debulking surgery. The study cohort will consist of participants with iron deficiency without anemia (defined below) prior to starting chemotherapy. Iron deficient participants with anemia are already offered iron sucrose infusions as part of their standard of care treatment.

The study group will include participants with planned neoadjuvant chemotherapy and debulking surgery with a normal Hgb within 30 days of study enrollment. Iron studies including ferritin, transferrin, total iron binding capacity (TIBC), reticulocyte count and serum iron, will be performed on these participants for research purposes only. Consent will be obtained prior to drawing research-related iron studies. The majority of participants will have Hgb levels available in their records from the last 30 days, either from the UW, or from a referring institution. If this is not the case, pre-chemotherapy lab studies will be obtained the day of their visit, which would routinely include a Hgb level.

Participants will sign a consent to receive four IV iron sucrose transfusions, prior to their debulking surgery, and be followed for prospective data collection. Consent will be signed for the infusion and for prospective data collection related to future laboratory studies and rates of transfusion of blood products. Participants with a normal Hgb and normal iron studies will participate in the prospective data collection portion of this study only. Prospective data collection will continue until subjects have completed first-line chemotherapy.

Subjects will be enrolled until 21 evaluable participants have been enrolled. Evaluable participants will have true or functional iron deficiency without anemia and have received at least one IV iron sucrose infusion.

Iron studies will be repeated 21 days (+/- 7 days) after last infusion in participants who receive IV iron sucrose. Participants with persistent iron deficiency will be referred to hematology.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Unblinded, window of opportunity trial
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: IV Iron Sucrose
Four intravenous iron sucrose infusions prior to debulking surgery administered as four 200mg infusions, given no less than 7 days apart over a 30 day +/- 7 day period
Other: Iron Sucrose
Venofer (Iron Sucrose Injection USP) is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use.
Other Name: Venofer

Outcome Measures
Primary Outcome Measures :
  1. Rate of Peri-operative Blood Transfusion [ Time Frame: Within 72 hours of surgery, up to 5 weeks on study ]
    Defined as a transfusion of Packed Red Blood Cells (PRBCs) within 72 hours of surgery, in iron deficient ovarian cancer patients who receive IV iron sucrose therapy prior to surgery compared to a historical controls (historically 77%). The primary endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. Point estimates and exact 95% confidence intervals (CI) will be calculated.


Secondary Outcome Measures :
  1. Rate of Iron Deficiency Anemia [ Time Frame: up to 21 days following surgery ]
    The rate of iron deficiency anemia in all ovarian cancers patients at the University of Wisconsin. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.

  2. Rate of Resolution of Iron Deficiency Anemia After Intervention [ Time Frame: up to 21 days following surgery ]

    Iron deficiency anemia is defined as ferritin > 30 ng/mL and iron saturation of < 50%.

    This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.


  3. Incidence of Treatment Emergent Adverse Events (AEs) [ Time Frame: up to 21 days following surgery ]

    Safety and Tolerability will be monitored by measuring adverse events data with date of onset (or worsening) on or after the start-date treatment with iron sucrose and end of study (post-operative visit (7 to 21 days following surgery). AEs are defined as mild, moderate and severe.

    This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent.
  • Has a diagnosis of true or functional iron deficiency without anemia within 30 days of treatment on this protocol

    • Iron deficiency without anemia (normal Hgb >/= 11.6 g/dL but ferritin < 30 ng/mL)
    • Functional iron deficiency without anemia (ferritin >30 ng/ml and iron saturation of <50%)
  • Has a clinical diagnosis of suspected epithelial ovarian cancer based on imaging studies, exam findings and laboratory values
  • Participants must be planning to receive neoadjuvant chemotherapy for their cancer diagnosis (NACT is defined as chemotherapy prior to debulking surgery)
  • Participants must be planning to undergo surgery for their cancer diagnosis
  • Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of first dose of IV iron sucrose. WOCBP is defined as patients who retain their reproductive structures and are not menopausal (defined as > age 50 with no menses for at least 1 year)
  • Participants of reproductive potential must agree to use effective birth control during study participation. Effective birth control is defined as any FDA approved contraceptive method

Exclusion Criteria:

  • Currently taken any form of oral or intravenous iron therapy. Patients must have discontinued iron therapy > 30 days from study entry
  • Current untreated or unstable heart disease
  • History of iron induced hypersensitivity or allergy
  • History of leukemia, lymphoma, or other myelodysplastic disorders
  • Prior diagnosis of hemochromatosis or hemoglobinopathy (e.g. thalassemia)
  • Any subject with immediate requirement for radiotherapy
  • Concomitant enrollment in another clinical trial interfering with endpoints on this study
  • Any medical condition which could compromise participation in the study according to the investigator's assessment
  • Female patient who is pregnant or breast-feeding
  • Patients unwilling or unable to comply with the protocol or unable to give informed consent
Contacts and Locations

Contacts
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Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu

Locations
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United States, Wisconsin
University of Wisconsin Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cancer Connect    800-622-8922    clinicaltrials@cancer.wisc.edu   
Principal Investigator: Lisa Barroilhet, MD         
Sub-Investigator: Joseph Connor, MD         
Sub-Investigator: Moniba Nazeef, MD         
Sub-Investigator: Janelle Sobecki-Rausch, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Layout table for investigator information
Principal Investigator: Lisa Barroilhet, MD University of Wisconsin, Madison
Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date December 30, 2020
Actual Study Start Date  ICMJE July 29, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
Rate of Peri-operative Blood Transfusion [ Time Frame: Within 72 hours of surgery, up to 5 weeks on study ]
Defined as a transfusion of Packed Red Blood Cells (PRBCs) within 72 hours of surgery, in iron deficient ovarian cancer patients who receive IV iron sucrose therapy prior to surgery compared to a historical controls (historically 77%). The primary endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. Point estimates and exact 95% confidence intervals (CI) will be calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
Rate of Peri-operative Blood Transfusion [ Time Frame: Within 72 hours of surgery, up to 5 weeks on study ]
Defined as a transfusion of PRBCs within 72 hours of surgery, in iron deficient ovarian cancer patients who receive IV iron sucrose therapy prior to surgery compared to a historical controls (historically 77%). The primary endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. Point estimates and exact 95% confidence intervals (CI) will be calculated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • Rate of Iron Deficiency Anemia [ Time Frame: up to 21 days following surgery ]
    The rate of iron deficiency anemia in all ovarian cancers patients at the University of Wisconsin. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
  • Rate of Resolution of Iron Deficiency Anemia After Intervention [ Time Frame: up to 21 days following surgery ]
    Iron deficiency anemia is defined as ferritin > 30 ng/mL and iron saturation of < 50%. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
  • Incidence of Treatment Emergent Adverse Events (AEs) [ Time Frame: up to 21 days following surgery ]
    Safety and Tolerability will be monitored by measuring adverse events data with date of onset (or worsening) on or after the start-date treatment with iron sucrose and end of study (post-operative visit (7 to 21 days following surgery). AEs are defined as mild, moderate and severe. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Rate of Iron Deficiency Anemia [ Time Frame: up to 21 days following surgery ]
    The rate of iron deficiency anemia in all ovarian cancers patients at the University of Wisconsin. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
  • Rate of Resolution of Iron Deficiency Anemia After Intervention [ Time Frame: up to 21 days following surgery ]
    Iron deficiency anemia is defined as ferritin > 30 ng/mL and iron saturation of < 50%. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
  • Safety and Tolerability of IV Iron Sucrose Therapy [ Time Frame: up to 21 days following surgery ]
    Safety and Tolerability will be monitored by measuring adverse events data with date of onset (or worsening) on or after the start-date treatment with iron sucrose and end of study (post-operative visit (7 to 21 days following surgery). AEs are defined as mild, moderate and severe. This endpoint will be summarized with descriptive statistics and conducted using a Fisher's exact test and exact binomial confidence intervals. In particular, point estimates and exact 95% confidence intervals (CI) will be calculated.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients
Official Title  ICMJE Evaluation and Treatment of Iron Deficiency in Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
Brief Summary This study tests the hypothesis that IV iron sucrose infusions given to iron deficient ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and decrease transfusion of packed red blood cells in the peri-operative period. 21 participants at least 18 years of age with epithelial ovarian cancer of any stage requiring neoadjuvant chemotherapy and surgery will be enrolled. Participants will be on study for a period of up to 3 months.
Detailed Description

Iron deficiency and anemia are common in cancer patients. Data from the University of Wisconsin (UW) suggest that more than 50% of ovarian cancer patients undergo blood transfusion during their cancer treatments. Transfusion rates are particularly high in patients who receive neoadjuvant chemotherapy (NACT), despite multiple opportunities to diagnose and treat anemia prior to surgery. Blood transfusions have been associated with worse survival in ovarian cancer patients. Seventy-seven percent of ovarian cancer patients who receive NACT at the UW are anemic prior to surgery, and the same percentage receive a perioperative blood transfusion, defined as a blood transfusion within 72 hours of surgery. Iron deficiency without anemia is also common in cancer patients, though little has been published regarding how frequently it occurs in ovarian cancer patients. Functional iron deficiency, a lack of iron incorporation into erythroid precursors despite adequate iron stores, is also common in cancer patients. Study investigators hypothesize that IV iron sucrose infusions given to iron deficient ovarian cancer patients prior to debulking surgery can improve pre-operative iron stores and decrease transfusion of packed red blood cells in the peri-operative period.

Eligible participants will have a new epithelial ovarian cancer diagnosis, with planned neoadjuvant chemotherapy and interval debulking surgery. The study cohort will consist of participants with iron deficiency without anemia (defined below) prior to starting chemotherapy. Iron deficient participants with anemia are already offered iron sucrose infusions as part of their standard of care treatment.

The study group will include participants with planned neoadjuvant chemotherapy and debulking surgery with a normal Hgb within 30 days of study enrollment. Iron studies including ferritin, transferrin, total iron binding capacity (TIBC), reticulocyte count and serum iron, will be performed on these participants for research purposes only. Consent will be obtained prior to drawing research-related iron studies. The majority of participants will have Hgb levels available in their records from the last 30 days, either from the UW, or from a referring institution. If this is not the case, pre-chemotherapy lab studies will be obtained the day of their visit, which would routinely include a Hgb level.

Participants will sign a consent to receive four IV iron sucrose transfusions, prior to their debulking surgery, and be followed for prospective data collection. Consent will be signed for the infusion and for prospective data collection related to future laboratory studies and rates of transfusion of blood products. Participants with a normal Hgb and normal iron studies will participate in the prospective data collection portion of this study only. Prospective data collection will continue until subjects have completed first-line chemotherapy.

Subjects will be enrolled until 21 evaluable participants have been enrolled. Evaluable participants will have true or functional iron deficiency without anemia and have received at least one IV iron sucrose infusion.

Iron studies will be repeated 21 days (+/- 7 days) after last infusion in participants who receive IV iron sucrose. Participants with persistent iron deficiency will be referred to hematology.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Unblinded, window of opportunity trial
Masking: None (Open Label)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Epithelial Ovarian Cancer
  • Anemia
  • Iron Deficiency Anemia
Intervention  ICMJE Other: Iron Sucrose
Venofer (Iron Sucrose Injection USP) is a brown, sterile, aqueous, complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use.
Other Name: Venofer
Study Arms  ICMJE Experimental: IV Iron Sucrose
Four intravenous iron sucrose infusions prior to debulking surgery administered as four 200mg infusions, given no less than 7 days apart over a 30 day +/- 7 day period
Intervention: Other: Iron Sucrose
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2023
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Provide written informed consent.
  • Has a diagnosis of true or functional iron deficiency without anemia within 30 days of treatment on this protocol

    • Iron deficiency without anemia (normal Hgb >/= 11.6 g/dL but ferritin < 30 ng/mL)
    • Functional iron deficiency without anemia (ferritin >30 ng/ml and iron saturation of <50%)
  • Has a clinical diagnosis of suspected epithelial ovarian cancer based on imaging studies, exam findings and laboratory values
  • Participants must be planning to receive neoadjuvant chemotherapy for their cancer diagnosis (NACT is defined as chemotherapy prior to debulking surgery)
  • Participants must be planning to undergo surgery for their cancer diagnosis
  • Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to administration of first dose of IV iron sucrose. WOCBP is defined as patients who retain their reproductive structures and are not menopausal (defined as > age 50 with no menses for at least 1 year)
  • Participants of reproductive potential must agree to use effective birth control during study participation. Effective birth control is defined as any FDA approved contraceptive method

Exclusion Criteria:

  • Currently taken any form of oral or intravenous iron therapy. Patients must have discontinued iron therapy > 30 days from study entry
  • Current untreated or unstable heart disease
  • History of iron induced hypersensitivity or allergy
  • History of leukemia, lymphoma, or other myelodysplastic disorders
  • Prior diagnosis of hemochromatosis or hemoglobinopathy (e.g. thalassemia)
  • Any subject with immediate requirement for radiotherapy
  • Concomitant enrollment in another clinical trial interfering with endpoints on this study
  • Any medical condition which could compromise participation in the study according to the investigator's assessment
  • Female patient who is pregnant or breast-feeding
  • Patients unwilling or unable to comply with the protocol or unable to give informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cancer Connect 800-622-8922 clinicaltrials@cancer.wisc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03933813
Other Study ID Numbers  ICMJE UW18106
2019-0022 ( Other Identifier: Institutional Review Board )
A532820 ( Other Identifier: UW Madison )
SMPH/OB-GYN/GYN ONCOLOGY ( Other Identifier: UW Madison )
NCI-2019-02185 ( Registry Identifier: NCI Trial ID )
Protocol Version 8/15/2019 ( Other Identifier: UW Madison )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lisa Barroilhet, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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