Effect of Intravenously Iron Infusion on the Prevention and Treatment of Anemia in Ovarian Cancer

The Effect Of Intravenous Iron In Treating Anemia In Ovarian Cancer Patients In Saskatchewan: A Phase-III, Open-Label, Randomized Trial (IIOVS-01)

Cancer related anemia (CRA) is a common sign occurring in more than 30% of patients at diagnosis, prior to initiation of antineoplastic therapy. Anemia is known to impact survival, disease progression, treatment efficacy, and the patient's quality of life.

Proinflammatory cytokines, mainly IL-6, which are released by both tumor and immune cells, play a pivotal action in CRA etiopathogenesis: they promote alterations in erythroid progenitor proliferation, erythropoietin (EPO) production, survival of circulating erythrocytes, iron balance, redox status, and energy metabolism, all of which can lead to anemia. Chronic inflammatory conditions such as cancer influences a compromised nutritional status, which in-turn may contribute to anemia.

This study aims to study the role of intravenous (IV) iron infusion in the management of anemia presented in patients previously treated or currently being treated for ovarian cancer. The study aims to identify the safety and efficacy of IV iron infusion on anemia in ovarian cancer patients, and the effect on quality of life and overall survival

Study Overview

• Status: Not yet recruiting
• Conditions: Anaemia in Ovarian Carcinoma
• Intervention / Treatment: Drug: IV iron

Detailed Description

This is an open label, prospective, randomized [1:1] controlled, Phase III study of Iron Sucrose, Iron Gluconate or Iron Isomaltoside (Treatment group A) versus No Iron Infusion treatment (Control group B) in participants diagnosed with ovarian cancer and with iron deficiency anemia. The primary objective of the study is to assess the efficacy of iron infusion, as measured by the primary endpoint, of Group A versus Group B.

The study treatment is divided into two groups (Arms):

Group A: Treatment study group

All patients will be treated with iron infusion for Hgb lower than 100 g/L and/or TSAT < 20%. Blood transfusion may also be given based on physician's discretion whenever indicated:

1. When Hgb level is < 70 g/L or in case of emergency and/or rapid blood loss.
2. Blood transfusion may be given to keep active treatment (chemotherapy, surgery, PARP inhibitors, hormonal, radiation) intervals as scheduled and not to exceed the maximum 4 weeks.
3. Based on current practice and NCCN guidelines, co-investigators/treating physicians are encouraged to avoid giving blood transfusion for Hgb >70g/L, provided the patient is stable and asymptomatic.
4. Blood transfusion can be combined with iron infusion.
5. Blood transfusion can be given when indicated if there is lack of response to iron infusion. Expected iron infusion response is expected at 8 weeks or less after treatment (from the preceding dose of a single IV iron order/treatment). For example, Isomatoside, monoferric is given as one dose, where iron gluconate is fractionated over 6 doses and iron sucrose is fractionated into 3 doses.

Group B: Control group

1. May receive blood transfusion when Hgb level is <70 g/L or in case of emergency and/or rapid blood loss.
2. Based on current practice and NCCN guidelines, co-investigators/treating physicians are encouraged to avoid giving blood transfusion for Hgb >70 g/L, provided the patient is stable and asymptomatic.

3. The decision to give blood transfusion for Hgb >70 g/L shall be based on the treating physician's discretion:

   1. symptomatic patient
   2. to maintain active treatment schedule
   3. to prepare the patient for surgery or an interventional procedure

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Maryam Al-Hayki; Phone Number: 306 766 2213; Email: maryam.al-hayki@saskcancer.ca
• Study Contact Backup: Name: Rashmi Nagaraj; Phone Number: 306 966 3374; Email: rashmi.nagaraj@usask.ca

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
      • Contact: Maryam Al-Hayki; Phone Number: 3067662213; Email: maryam.al-hayki@saskcancer.ca
      • Principal Investigator: Maryam Al-Hayki
      • Sub-Investigator: Shaina Lee
      • Sub-Investigator: Brent Jim
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
      • Contact: Maryam Al-Hayki; Phone Number: 3067662213; Email: maryam.al-hayki@saskcancer.ca
      • Principal Investigator: Maryam Al-Hayki
      • Sub-Investigator: Laura Hopkins
      • Sub-Investigator: Vickie Martin
      • Sub-Investigator: Jennifer Brown Broderick

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. Age and Sex: Female participants aged 18 years or more (>/=18 years) at the time of informed consent.
2. Type of Participant: Participants who are willing and able to comply with all scheduled visits, laboratory tests, lifestyle considerations, treatment plan, and any other study procedures.
3. Disease Characteristics: Histologically confirmed primary epithelial invasive ovarian cancer of any grade, including serous, mucinous, endometrioid, clear cell, transitional, squamous and carcinosarcoma. Cancer must be FIGO stage IC-IV.

4. Presence of measurable disease per RECIST v1.1, as assessed by investigator and evidenced by available baseline tumor scan. At least 1 target lesion of 10mm.

   Note: Baseline Scan is defined as the last scan prior to the date of randomization.

5. Patients should be eligible for active cancer treatment ECOG less or equal to 2 and life expectancy must be more than 6 months.
6. Received no more than two (2) systemic lines of chemotherapy (to allow for a ~3 years follow up).
7. Patients on any active cancer treatment or with history of previous chemotherapy, surgery, radiation, PARP (Poly-ADP Ribose polymerase), biologics and hormonal treatment.
8. Patients on neoadjuvant, adjuvant, advanced cancer treatment.
9. Perioperative patients having upfront surgery (can be randomized after frozen section) or at interval or secondary debulking surgery.
10. Informed Consent: Capable of giving signed informed consent.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

1. Patients would not consent for IV iron infusion or blood transfusion (Example: Jehovah's Witness).
2. History of known severe hypersensitivity to IV iron transfusion with the study iron products.

3. Medical conditions with contraindication to IV iron infusion or blood transfusion (Example:

   iron overload, hemosiderosis, decompensated liver cirrhosis or active hepatitis.)

4. Palliative patients with life expectancy 6 months or less.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iron Infusion Arm; Group A: Treatment study group All patients will be treated with iron infusion for Hgb lower than 100 g/L and/or TSAT < 20%.	Drug: IV iron; Intravenous Iron supplement; Other Names: iron isomaltoside (Monofer, Monoferric) ferric gluconate (FG) iron sucrose (IS)
No Intervention: No Iron Infusion; Group B: No iron Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of Hgb>100g/L (Hemoglobin)	by ongoing monitoring of patient Hgb status for patients on active treatment every 3 weeks and patients in follow-up every 3 months. Effect of Iron infusion on response to chemotherapy.	every 3 weeks during treatment, then every 3 months during follow-up, up to 3 years.
Safety of IV iron	Measure the safety of IV iron including type and frequency of AEs, SAEs, TEAEs, discontinuation due to AEs and outcome of AE treatment. It will be compared to AEs (including frequency, SAEs, TEAs, discontinuation due to AEs and outcome of AEs treatment) of blood transfusion and it will be compared to literature data on IV iron.	At every visit through study completion, up to 3 years.
Efficiency of IV iron	To assess the efficiency of IV iron, Hgb will be frequently assessed as per the study protocol. Hgb will be compared to baseline level, looking at substantial increase of Hgb of about 20 g/L increase within maximum 8 weeks (study estimated response time).	every 3 weeks during treatment, then every 3 months during follow-up, up to 3 years.
Time to response	Time to response will be measured in every patient treated with IV iron from the time of treatment until substantial increase in Hgb from baseline 20 g/L. Hgb will be checked just prior to IV iron and then biweekly until week 8 or whenever Hgb rises at least by 20 g/L	Hgb will be checked just prior to treatment and then biweekly until week 8 or whenever Hgb rises at least by 20 g/L through the treatment period, upto 3 years.
Delay In Chemotherapy	Timing of chemotherapy will be recorded and that will be compared to the standard treatment protocol. Any delay of chemotherapy schedule due to "anemia" will be flagged and recorded in all participants. These data will be compared between the two study groups.	Throughout study completion, up to 3 years.
Change in QOL (quality of Life)	To measure any change from baseline QOL of both study groups and compare the difference of QOL in Group A (the group receiving IV infusion to correct anemia) compared to Group B. This will be done by comparing scores on the QOL questionnaire.	At screening, then Post treatment (every 6 months) up to 3 years.

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Maryam Al-Hayki, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Estimated): February 29, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 27, 2023
• First Submitted That Met QC Criteria: February 5, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia; Physiological Effects of Drugs; Trace Elements; Micronutrients; Hematinics; Iron isomaltoside 1000; Iron; Ferric Oxide, Saccharated; Ferric gluconate
• Other Study ID Numbers: IIOVS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No