Ferric Derisomaltose for Gynecologic Cancers

(FORGE II Trial)

Recruiting at 1 trial location

Overseen By Michelle Kan

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AHS Cancer Control Alberta

Must not be taking: Erythropoietin, IV iron, Immunosuppressants, others

Disqualifiers: Iron overload, Liver disease, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

82 Participants Needed

Trial Summary

What is the purpose of this trial?

Iron deficiency has been reported in approximately 35% of patients with a gynecologic malignancy. Blood transfusions are known to be immunosuppressive and carry immediate and long-term risks. Pre-operative blood transfusion in gynecologic oncology patients is associated with higher rates of surgical site infection, length of stay, composite morbidity, cancer recurrence, and mortality. Pre-operative intravenous iron formulations have been shown in benign gynecology and other surgical specialities to increase pre-operative hemoglobin and decrease post-operative transfusion rates. This is a randomized double-blinded clinical trial evaluating the effects of treating patients undergoing gynecologic oncology surgery with intravenous ferric derisomaltose to correct pre-operative iron-deficiency anemia. The 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.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive therapy or receiving renal dialysis, you may not be eligible to participate.

What data supports the effectiveness of the drug Ferric Derisomaltose for gynecologic cancers?

Ferric Derisomaltose is effective in treating iron deficiency anemia, which is common in gynecologic cancer patients, by rapidly replenishing iron levels with a good safety profile. It has been shown to decrease the need for blood transfusions in cancer patients undergoing chemotherapy, suggesting potential benefits in the preoperative period for gynecologic oncology surgery. ^{1 2 3 4 5}

Is ferric derisomaltose safe for use in humans?

Ferric derisomaltose is generally considered safe for use in humans, with a low incidence of adverse reactions. Anaphylaxis (a severe allergic reaction) is extremely rare, and other reactions like hypophosphatemia (low phosphate levels in the blood) are infrequent compared to other iron treatments. ^{2 3 4 6 7}

How is the drug Ferric Derisomaltose unique for treating gynecologic cancers?

Ferric Derisomaltose is unique because it is an intravenous iron treatment that can rapidly replenish iron levels in a single high-dose infusion, which is particularly beneficial for gynecologic cancer patients with iron-deficiency anemia who may not respond well to oral iron due to side effects and absorption issues. ^{1 4 6 8 9}

Eligibility Criteria

This trial is for adults over 18 with iron-deficiency anemia who are scheduled for elective major gynecologic oncology surgery within the next 28-90 days. They must have low hemoglobin and transferrin saturation levels, not be pregnant, and agree to use contraception. Exclusions include other causes of anemia, hypersensitivity to the drug being tested, certain infections or liver diseases, recent iron therapy or erythropoietin use, pregnancy/lactation, psychiatric/social issues affecting compliance.

Inclusion Criteria

I received the study treatment between 21 and 90 days before my scheduled surgery.

Signed written informed consent prior to initiation of any study specific activities/procedures

WOCBP must adhere to the contraception requirement from screening throughout the study period until 6 weeks post treatment

Exclusion Criteria

My cervical cancer is at stage 2A or more advanced.

I have a long-term liver condition or active hepatitis.

You have anemia caused by something other than the condition being studied, such as a deficiency in B12 or folate, or a blood disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive intravenous ferric derisomaltose or placebo to correct pre-operative iron-deficiency anemia

21-90 days

1 visit (in-person)

Surgery

Participants undergo gynecologic oncology surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery, including assessments of postoperative complications and quality of life

28-60 days

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Ferric Derisomaltose
• Placebo

Trial Overview The trial tests if ferric derisomaltose can correct pre-operative iron-deficiency anemia better than a placebo in patients undergoing surgery for gynecologic malignancy. It's randomized and double-blinded; participants won't know if they're getting the actual drug or a dummy treatment.

Participant Groups

Group I: Iron Therapy Arm Experimental Treatment 1 Intervention

500 or 1000mg of IV Ferric Derisomaltose in 100mL normal saline will be administered intravenously over 1 hour. Participants with bodyweight \<50kg will receive 500mg, participants with bodyweight \>50kg will receive 1000mg to ensure no patient exceeds the manufacturer's recommended dose of 20mg/kg bodyweight.

Group II: Placebo Arm Placebo Group 1 Intervention

100mL of normal saline will be administered intravenously over 1 hour between 21 and 90 days preceding surgical intervention.

Ferric Derisomaltose is already approved in United States, European Union for the following indications:

Approved in United States as Monoferric for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Approved in European Union as Monofer for:

• Iron deficiency anemia in adults with intolerance to oral iron or unsatisfactory response to oral iron or non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Who Is Running the Clinical Trial?

AHS Cancer Control Alberta

Lead Sponsor

Trials

188

Recruited

26,900+

Findings from Research

Ferric derisomaltose is an effective intravenous iron treatment that allows for complete iron repletion in a single high-dose infusion, making it a rapid and cost-effective option for patients with iron deficiency.

It has a good safety profile, with rare occurrences of serious reactions like anaphylaxis and lower rates of hypophosphatemia compared to older intravenous iron formulations, indicating its suitability for a wide range of patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. Kassianides, X., Bodington, R., Bhandari, S.[2021]

In a study of 30 cancer patients with gastrointestinal tumors undergoing chemotherapy, intravenous iron (ferric carboxymaltose) significantly improved hemoglobin levels and other iron status parameters over a treatment period of 12-14 weeks.

The treatment was well tolerated, with only one reported adverse event, indicating that ferric carboxymaltose is a safe and effective option for managing iron-deficiency anemia in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of intravenous iron in the treatment of anemia in patients with gastrointestinal tract tumors undergoing chemotherapy: a single-center, observational study. Lima, J., Gago, P., Rocha, M., et al.[2022]

In a large study of 7354 patients receiving ferric derisomaltose (FDI) for iron deficiency, the incidence of adverse reactions was very low, with only 1.7% experiencing any reactions and less than 0.1% having anaphylaxis, indicating that FDI is a safe treatment option.

Significant improvements in hemoglobin and ferritin levels were observed by Month 4 post-infusion, particularly in patients from surgical specialties, suggesting that FDI is effective in increasing iron levels in diverse patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK. Sinclair, RCF., Nadaraja, S., Kennedy, NA., et al.[2023]

Ferric derisomaltose (FDI) significantly increased hemoglobin levels in Japanese patients with iron-deficiency anemia (IDA) related to gastrointestinal diseases, with an average increase of 4.33 g/dL across all participants in a phase III study involving 40 patients.

The treatment was found to be safe, with 60% of patients experiencing treatment-emergent adverse events, but no serious or unexpected safety issues were reported, indicating a favorable safety profile for both intravenous bolus injection and drip infusion methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for iron-deficiency anemia associated with gastrointestinal diseases: a single-arm, randomized, uncontrolled, open-label study. Kawabata, H., Tamura, T., Tamai, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Ferric derisomaltose and Outcomes in the Recovery of Gynecologic oncology: ERAS (Enhanced Recovery After Surgery) (FORGE) - a protocol for a pilot randomised double-blinded parallel-group placebo-controlled study of the feasibility and efficacy of intravenous ferric derisomaltose to correct preoperative iron-deficiency anaemia in patients undergoing gynaecological oncology surgery. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Retrospective cohort study comparing the adverse reactions and efficacy of intravenous iron polymaltose with ferric carboxymaltose for iron deficiency anemia. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Applying reflective multicriteria decision analysis to understand the value of therapeutic alternatives in the management of gestational and peripartum anaemia in Spain. [2023]

4. England pubmed.ncbi.nlm.nih.gov

An evaluation of ferric derisomaltose as a treatment for anemia. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Role of intravenous iron in the treatment of anemia in patients with gastrointestinal tract tumors undergoing chemotherapy: a single-center, observational study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Real-world experience of intravenous ferric derisomaltose evaluated through safety and efficacy reporting in the UK. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose for iron-deficiency anemia associated with gastrointestinal diseases: a single-arm, randomized, uncontrolled, open-label study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France. [2022]