Ferric Derisomaltose/Iron Isomaltoside and Outcomes in the Recovery of Gynecologic Oncology ERAS (FORGE)

Feasibility and Efficacy of Intravenous Ferric Derisomaltose to Correct Pre-operative Iron-deficiency Anemia in Patients Undergoing Gynecologic Oncology Surgery: a Pilot Randomized Double Blinded Parallel Group Placebo-controlled Study

Iron deficiency has been reported in up to 35% of patients with a gynecologic malignancy. These patients often require surgical intervention to determine the stage and to treat their illness. Blood transfusions occur in approximately 14% of these surgeries and carry immediate and long-term risks, including surgical site infection, cancer recurrence, and increased surgical length of stay. Intravenous iron formulations have the potential to rapidly correct anemia in patients with gynecologic malignancy and potentially decrease blood transfusion and complications following surgery. This prospective, randomized, placebo-controlled, double blind study aims to assess the effectiveness of preoperative ferric derisomaltose/iron isomaltoside compared to placebo in correcting preoperative hemoglobin in patients undergoing surgery for gynecologic malignancy. The primary outcome is to assess the effectiveness of this formulation on pre-operative hemoglobin, and the feasibility of a larger, outcomes based, study in the future. Exploratory outcomes are to assess the effect of preoperative intravenous iron on surgical length of stay, complications, and patient-reported quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Gynecologic Cancer; Surgery; Anemia, Iron Deficiency
• Intervention / Treatment: Drug: Ferric Derisomaltose Injection; Drug: Normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. At least 18 years of age and signed written informed consent

2. Patients undergoing elective major surgery on the gynecologic oncology service with the following criteria will be considered for inclusion:

   1. The indication for the operation may be for suspected or proven gynecologic malignancy.
   2. Major surgery is defined as an operation of a duration of 1 hour or greater, with an Aletti complexity score of at least 1[19].
   3. The expected time from recruitment to surgery is at least 28 days.
3. Screening haemoglobin less than 120g/L and transferrin saturation (TSAT) <20%
4. Randomization and administration of study infusion a minimum of 21 days and maximum 90 days before planned operation.
5. Negative pregnancy test for women of childbearing potential (within last 7 days), and agree to use effective form of contraception until 6 weeks post treatment (if applicable)
6. Laboratory data used for determination of eligibility at the baseline visit must not be older than 4 weeks.

Exclusion Criteria:

1. Known history of acquired iron overload, or family history of haemochromatosis or thalassemia, or TSAT >50%
2. Known alternative cause for anemia (e.g. B12 or folate deficiency, or haemoglobinopathy)
3. Known hypersensitivity to FDI or its excipients
4. Temperature >38 C or patient on non-prophylactic antibiotics
5. Known chronic liver disease or active hepatitis
6. Received erythropoietin or IV iron therapy in previous 12 weeks
7. If LFT's are ordered, either clinically indicated or for chemotherapy, and screening alanine transaminase (ALT) or aspartate transaminase (AST) is above three times the upper limit of normal (ULN) range
8. Immunosuppressive therapy (for solid organ transplant), or renal dialysis (current, or planned within next 12 months)
9. Unfit for elective surgery
10. Pregnancy or lactation
11. Unable to fully comprehend and/or perform study procedures
12. Cervical cancer with a clinical stage of 2A or greater.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferric derisomaltose; 1000mg of intravenous Ferric derisomaltose/Iron isomaltoside in 100mL of normal saline will be administered 21-90 days prior to planned surgery for gynecologic malignancy as a single dose.	Drug: Ferric Derisomaltose Injection; 1000mg of ferric derisomaltose in 100mL of normal saline by intravenous infusion; Other Names: Monofer; Monoferric; iron isomaltoside
PLACEBO_COMPARATOR: Placebo; 100mL of normal saline will be administered 21-90 days prior to planned surgery for gynecologic malignancy as a single dose.	Drug: Normal saline; 100 mL of 0.9% normal saline (w/v) by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preoperative hemoglobin level	Hemoglobin measured, in g/L, following intervention prior to planned gynecologic surgery.	0 to 3 days prior to planned surgical intervention

Collaborators and Investigators

• Sponsor: Alberta Health Services, Calgary
• Collaborators: Pharmacosmos A/S

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 30, 2022
• Primary Completion (ANTICIPATED): September 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 19, 2022
• First Posted (ACTUAL): July 20, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: iron isomaltoside; intravenous iron; Ferric derisomaltose
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Hematinics; Iron isomaltoside 1000
• Other Study ID Numbers: FORGEII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No