IV Iron Replacement for Anemia

(Iron-RANC Trial)

Overseen By Ryan Romasko

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fox Chase Cancer Center

Must not be taking: Erythropoietin stimulating agents

Disqualifiers: Active infection, Heart failure, Angina, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of an intravenous (IV) iron treatment called Venofer for people with certain types of cancer who experience anemia (low red blood cell count) during chemotherapy. The goal is to determine if this treatment can boost iron levels and improve overall health before surgery. The trial seeks participants with thoracic, breast, gastrointestinal (GI), or genitourinary (GU) cancers who are receiving chemotherapy and have anemia not caused by other factors. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially improve their health outcomes.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using erythropoietin stimulating agents, you must not have used them within 4 weeks before the trial unless you have chronic kidney disease.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that Venofer (iron sucrose) is safe for many patients. One study, which included over 1,000 individuals with kidney problems, found that a small number, more than 1%, experienced side effects such as heart issues and infections. However, these side effects are uncommon. Venofer is also eliminated from the body fairly quickly, meaning it doesn't remain in the bloodstream for long, which is a positive safety indicator. Overall, Venofer has a strong safety record from its past use in treating anemia in patients with various medical conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard oral iron supplements commonly used to treat anemia, Venofer is administered as an intravenous (IV) infusion. This method allows for a more direct and potentially faster replenishment of iron levels in the body, which can be particularly beneficial for individuals who have difficulty absorbing iron through their digestive system. Researchers are excited about Venofer because its active ingredient, iron-sucrose, may offer improved efficacy and a quicker response time compared to traditional oral iron pills, potentially leading to faster relief from anemia symptoms.

What evidence suggests that Venofer might be an effective treatment for anemia?

Research shows that Venofer, a form of iron known as iron sucrose, effectively treats iron deficiency anemia. Studies have consistently found that it raises iron levels in the body, improving symptoms like tiredness and weakness. Participants in this trial will receive Venofer, and patients receiving iron sucrose have experienced improved blood iron levels, making it a reliable choice for those with iron deficiency. Although limited data exists specifically for cancer patients undergoing chemotherapy, the treatment's success in other groups suggests it could also benefit those receiving cancer treatment. Overall, Venofer has a strong record for increasing iron and reducing anemia symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Iberia Sosa, MD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with anemia (Hgb <10.5 g/dL) during chemotherapy, low iron levels, and who are planning surgery after chemo for breast, thoracic, GI or GU cancers. They must understand and sign consent forms. Excluded are those on certain anemia drugs, with uncontrolled illnesses, recent iron infusions, pregnant/breastfeeding women, other causes of anemia or known allergy to Iron sucrose.

Inclusion Criteria

I am receiving treatment before surgery for cancer in my breast, chest, stomach area, or urinary system.

Iron storage levels of ferritin <500 ng/mL and iron saturation <35%

Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria

I do not have an infection that affects my whole body.

Known hypersensitivity to Iron sucrose

Pregnant or breast feeding. Refer to section 4.4 for further detail

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous iron sucrose monotherapy and may undergo neoadjuvant chemotherapy, radiation, and immunotherapy

24 weeks

Weekly visits for iron infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hemoglobin levels and transfusion frequency

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Venofer

Trial Overview

The study tests the effectiveness of Venofer (intravenous iron sucrose) as a single therapy in reducing anemia for patients undergoing neoadjuvant chemotherapy before surgical cancer treatment. It's open-label at one institution aiming to see if this approach can improve patient outcomes.

How Is the Trial Designed?

Group I: Venofer treatment Experimental Treatment 1 Intervention

Venofer (iron-sucrose) 200mg (5 days) every week administered as an IV infusion

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

A review of intravenous iron formulations from 2001-2003 found that higher molecular weight iron dextran was associated with significantly more adverse drug events (ADEs) compared to lower molecular weight iron dextran, sodium ferric gluconate complex, and iron sucrose.

The overall rate of intravenous iron-related ADEs was very low at approximately 38 per million doses, with life-threatening ADEs being much less common in non-dextran formulations, highlighting their safety profile despite the high cost of preventing these events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on adverse drug events associated with parenteral iron. Chertow, GM., Mason, PD., Vaage-Nilsen, O., et al.[2022]

In a study of 100 patients with iron deficiency anemia, intravenous (IV) iron sucrose significantly increased hemoglobin levels more than oral iron supplements, with hemoglobin rising to 11.66 g/dL in the IV group compared to 9.69 g/dL in the oral group by day 28.

IV iron therapy was found to be safe, with fewer adverse effects compared to oral iron; while some patients experienced arthralgia and hypotension, no cases of anaphylaxis were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral versus intravenous iron therapy in iron deficiency anemia: An observational study. Das, SN., Devi, A., Mohanta, BB., et al.[2022]

Intravenous iron sucrose (Venofer®) is an effective treatment for iron deficiency and iron-deficiency anemia, especially in patients who cannot tolerate or respond to oral iron, and is now considered first-line therapy in conditions like end-stage kidney disease and chronic heart failure.

Iron sucrose has a strong safety profile and rapidly improves hemoglobin and iron levels, but there are concerns about substituting it with similar products due to potential differences in efficacy and safety, highlighting the complexity of its nanomedicine formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency. Macdougall, IC., Comin-Colet, J., Breymann, C., et al.[2023]

A study comparing the original iron sucrose product Venofer® and the generic version AZAD (ISA) found no significant differences in bioavailability, toxicity, or stability in human cell models, indicating that ISA is comparable to Venofer® in these aspects.

The results suggest that ISA has identical physico-chemical properties and bioavailability in vitro, providing a strong foundation for future clinical trials to assess the efficacy and safety of this generic iron sucrose formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability and stability of intravenous iron sucrose originator versus generic iron sucrose AZAD. Praschberger, M., Cornelius, C., Schitegg, M., et al.[2018]

A retrospective study of 238 hospitalized adults with iron deficiency anemia showed that a pharmacist-assisted total dose infusion (TDI) protocol for iron sucrose significantly increased hemoglobin levels by an average of 2.1 g/L (P < .001).

The protocol was well tolerated, with only 15 patients (2.9%) experiencing adverse effects, primarily nausea, and no cases of anaphylaxis or liver function test increases were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective Safety Evaluation of a Pharmacist-Assisted Total Dose Iron Sucrose Protocol in Hospital Inpatients With Iron Deficiency Anemia. Wall, G., Sharma, V., Taylor, MJ., et al.[2022]

Intravenous iron sucrose (Feronia IV) significantly increased hemoglobin levels in women with iron deficiency anemia, with an average rise of 2.43 gm% after 4 weeks of treatment across 143 analyzable cases.

The treatment was found to be safe, as no serious adverse reactions were reported, making it an effective option for managing iron deficiency anemia in gynecological and obstetric practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of intravenous iron sucrose in the management of anemia in gynecological and obstetrical practice. Dewan, B., Philipose, N., Balasubramanian, A.[2022]

In a multicenter North American trial involving 77 patients with dialysis-associated anemia, iron sucrose therapy significantly increased hemoglobin levels after just three doses and maintained elevated levels for at least five weeks after the final dose.

The study found that administering 1,000 mg of iron sucrose in 10 undiluted IV doses was safe, with no serious adverse reactions or changes in blood pressure, even in patients with previous sensitivities to iron dextran or other drug allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of iron sucrose for iron deficiency in patients with dialysis-associated anemia: North American clinical trial. Charytan, C., Levin, N., Al-Saloum, M., et al.[2022]

In a study of 1500 patients undergoing maintenance haemodialysis, proactively administered high-dose iron sucrose resulted in significantly higher monthly iron doses compared to reactively administered low-dose iron sucrose, suggesting better management of iron levels.

Patients receiving high-dose iron sucrose experienced fewer adverse events related to heart issues and hospitalizations, indicating that this proactive approach may enhance safety and efficacy in treatment without increasing mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose versus low-dose iron sucrose in individuals undergoing maintenance haemodialysis: a retrospective study. Liu, L., Cheng, H., Lv, Y., et al.[2022]

Intravenous iron, particularly iron sucrose, can lead to oxidative stress and endothelial dysfunction in patients with chronic kidney disease, raising concerns about its long-term safety.

Iron sucrose infusion has been associated with acute renal injury and inflammation, as indicated by increased levels of urinary albumin and specific enzymes, suggesting a need for further investigation into the long-term effects of intravenous iron treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute injury with intravenous iron and concerns regarding long-term safety. Bishu, K., Agarwal, R.[2022]

Intravenous iron III-hydroxide saccharate was found to be an effective treatment for adult patients with iron deficiency anemia who did not respond well to oral iron therapy, with a significant increase in hemoglobin levels observed post-treatment.

Out of 25 patients studied, 68% achieved correction of anemia, and none required blood transfusions, highlighting the safety and efficacy of this treatment option, especially for those with severe anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the efficacy of intravenous iron III-hydroxide saccharate for treating adult patients with iron deficiency anemia]. Cançado, RD., Brasil, SA., Noronha, TG., et al.[2019]

Oral iron treatments have low bioavailability (10-20%) and are often not taken correctly by patients, leading to reduced effectiveness and digestive issues.

Intravenous treatments like Venofer (hydroxide ferric saccharose) are currently the only option in France, but they are significantly more expensive; other intravenous iron products have shown similar efficacy and safety, suggesting alternatives may be available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatments of the martial deficiencies: preparations available in France]. Ranfaing, E.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7467495/

Iron Sucrose: A Wealth of Experience in Treating ...

As summarized in Table 2, studies have consistently reported that iron sucrose is an effective treatment for iron deficiency/iron-deficiency anemia in patients ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468024925000543

Systematic Review of the Effects of Iron on Cardiovascular ...

Iron therapy may reduce the risk of heart failure and cardiovascular death in patients with CKD. Randomized trials evaluating the effects of iron on clinical ...

3.

academic.oup.com

academic.oup.com/ndt/article/35/6/946/5817329

Iron kinetics following treatment with sucroferric oxyhydroxide ...

Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal ...

4.

velphorohcp.com

velphorohcp.com/content/dam/velphorohcp/documents/coyne_2017.pdf

Real-world effectiveness of sucroferric oxyhydroxide in ...

We sought to assess the real-world effectiveness of sucroferric oxyhydroxide. (SO), an iron-based phosphate binder (PB), in control of serum ...

5.

ajkd.org

ajkd.org/article/S0272-6386(21)00955-0/fulltext

Recent and Emerging Therapies for Iron Deficiency in ...

This review describes diagnostic criteria for iron deficiency in chronic kidney disease, as well as mechanisms of functional and absolute iron deficiency and ...

6.

venofer.com

venofer.com/

Venofer® (iron sucrose) injection, USP | Official Site

In post-marketing safety studies of Venofer in 1,051 patients with HDD-CKD, adverse reactions reported by >1% were cardiac failure congestive, sepsis, and ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S1549963420300307

Factors influencing safety and efficacy of intravenous iron ...

This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12034885/

Systematic Review of the Effects of Iron on Cardiovascular ...

Iron therapy may reduce the risk of heart failure and cardiovascular death in patients with CKD. Randomized trials evaluating the effects of iron on clinical ...

9.

academic.oup.com

academic.oup.com/ndt/article/32/8/1330/3059437

Iron-related parameters in dialysis patients treated with ...

A large retrospective study of over 3000 US dialysis patients found that 3 months' treatment with sucroferric oxyhydroxide was associated with ...