Randomized Study Evaluating Agents Stimulants Erythropoiesis (ASE) Associated With Ferric Carboxymaltose (Ferinject ®) in Concomitant or Sequential Patients Treated for Cancer and With Anemia Associated With Functional Iron Deficiency

NCT ID: NCT02213653

Last Updated: 2015-04-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2014-11-30

Brief Summary

Anemia in patients with cancer is a common problem associated with an impaired quality of life.

Treatment with erythropoiesis stimulating agents (ESA) allows an increase in hemoglobin levels in 40-70% of patients and decreased transfusion requirements.

Absolute or functional iron deficiency is also common with about 30% of cancer patients with all histologies combined iron deficiency and anemia.

Several studies have shown the benefits of the combination of intravenous iron to erythropoiesis-stimulating agents in improving hemoglobin. However, none of them, to the investigators knowledge, has not been specifically performed on a population of patients with functional iron deficiency.

In addition, in clinical practice, this association is not carried out in particular because there is no dosage or consensus sequence for the administration of iron associated with ESAs.

Detailed Description

• Iron Deficiency and Cancer The literature review therefore presents uncertainties do not allow the routine application of intravenous iron associated with ESAs. The SOR also conclude that IV iron is "consider" if iron deficiency.

These uncertainties are the heterogeneity of the study populations, contradictory results and the use of patterns intravenous iron binding and non-standardized.

The investigators focus in this study in patients with chemotherapy-induced anemia with functional iron deficiency is a cause of lack of response to ESA. Indeed, patients with true iron deficiency seems to justify a routine iron supplementation. In contrast, patients without iron deficiency do not warrant formal way of initiating such treatment (although the literature is contradictory).

This study aims to evaluate, in patients with chemotherapy-induced anemia and functional iron deficiency, the efficacy and safety of the combination epoietin zeta + Iron in concomitant intravenous or sequential.

Because data RCP (Summary of Product Characteristics), ease of use, its safety profile, the ability to achieve higher doses of iron with a lower frequency and with better adherence, the ferric carboxymaltose was chosen as an intravenous iron. One specialty is available, the Ferinject ® (Laboratoires VIFOR Pharma).

The erythropoiesis-stimulating agent chosen in this study is epoietin zeta.

• Hepcidin and iron Hepcidin is a peptide hormone of 25 amino acids produced by the liver and considered as the central regulator of iron homeostasis in the body.

It works by controlling intestinal iron absorption and iron reuse by the reticuloendothelial system. Hepcidin acts by preventing the export of iron enterocytes, intestinal site of absorption of dietary iron, and macrophages, iron recycling site of hemoglobin, by binding to ferroportin present at the membrane these cells and by inducing its internalization and degradation.

Accordingly, hepcidin can be considered a hyposidérémiante hormone. The hepcidin rate is increased by the iron thereby limiting its accumulation and tissue damage associated with iron overload. Inversely, the rate is reduced hepcidin during increased iron as anemia needs, hypoxia, pregnancy or other situations of iron deficiency.

Moreover, hepcidin is strongly induced by inflammation. Thus, in pathological situations such as cancer, high levels of hepcidin explain well enough inflammatory anemia characterized by anemia, iron retention at storage proteins such as ferritin but also at the level of the reticuloendothelial system endothelial and a decrease in intestinal iron absorption.

Despite its importance in the pathophysiology of anemia of inflammation and a fortiori with iron deficiency anemia functional hepcidin is not measured in clinical routine. There is not, to the investigators knowledge, prospective data on its blood levels in situations of iron deficiency anemia in cancer patients functional and data on changes in hepcidin levels induced by treatment with intravenous iron or with erythropoietin.

Conditions

Solid Cancer Metastatic Disease; Lymphoid Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Concomitant iron and I.V. epoietin zeta

Group Type: EXPERIMENTAL

ARM A : IV iron + epoietin zeta

Intervention Type: DRUG

• Epoietin zeta at a dose of 450 IU / kg per week subcutaneously
• Carboxymaltose ferric (Ferinject ®) at week 1; Intravenous infusion not exceeding 1000 mg (administered once if weight> 50 kg, 500 mg twice otherwise, with an interval of one week between each administration).

• Renewable with a minimum of 4 weeks depending on the iron status (if CST <20% and absence of serum ferritin> 800) in the same manner as week 1.

Iron and I.V. epoietin zeta sequential

Group Type: EXPERIMENTAL

ARM B: IV iron + epoietin zeta sequence

Intervention Type: DRUG

• Epoietin zeta at a dose of 450 IU / kg per week subcutaneously started in week 7
• carboxymaltose ferric (Ferinject ®) at week 1

• Intravenous infusion not exceeding 1000 mg (administered once if weight> 50 kg, 500 mg twice otherwise, with an interval of one week between each administration).
• Renewable with a minimum of 4 weeks depending on the iron status (if CST <20% and absence of serum ferritin> 800) in the same manner as week 1.

Epoietin zeta

Group Type: ACTIVE_COMPARATOR

ARM C : single epoietin zeta

Intervention Type: DRUG

Epoietin zeta at a dose of 450 IU / kg per week subcutaneously begun in week 1

Interventions

ARM A : IV iron + epoietin zeta

• Epoietin zeta at a dose of 450 IU / kg per week subcutaneously
• Carboxymaltose ferric (Ferinject ®) at week 1; Intravenous infusion not exceeding 1000 mg (administered once if weight> 50 kg, 500 mg twice otherwise, with an interval of one week between each administration).

• Renewable with a minimum of 4 weeks depending on the iron status (if CST <20% and absence of serum ferritin> 800) in the same manner as week 1.

Intervention Type: DRUG

ARM B: IV iron + epoietin zeta sequence

• Epoietin zeta at a dose of 450 IU / kg per week subcutaneously started in week 7
• carboxymaltose ferric (Ferinject ®) at week 1

• Intravenous infusion not exceeding 1000 mg (administered once if weight> 50 kg, 500 mg twice otherwise, with an interval of one week between each administration).
• Renewable with a minimum of 4 weeks depending on the iron status (if CST <20% and absence of serum ferritin> 800) in the same manner as week 1.

Intervention Type: DRUG

ARM C : single epoietin zeta

Epoietin zeta at a dose of 450 IU / kg per week subcutaneously begun in week 1

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient> 18 years;
• Metastatic or locally advanced non-curable undergoing chemotherapy or lymphoid disease for which chemotherapy is indicated solid cancerous disease;
• Patient for which there are at least 3 cycles or 3 months of chemotherapy;
• Haemoglobin between 8.5 and 11 g / dL;
• Functional martial deficiency defined by a coefficient of transferrin saturation and serum ferritin ≤ 20% between 100 and 800 mg / L;
• Life expectancy> 3 months;
• ECOG ≤ 2.

Exclusion Criteria

• Documented hemochromatosis ;
• AST and / or ALT> 2.5N;
• Renal impairment with Cockcroft clearance <30 mL / min;
• Vitamin B12 deficiency or folate;
• Hemolysis;
• Infectious disease being untreated;
• Haemorrhagic syndrome related or not with the tumor;
• Hypersensitivity to Ferinject ® or any of the excipients;
• Land atopic asthma or eczema known
• Contraindication to EPO;
• Taking a supplement to oral iron;
• Treatment with EPO within 6 months prior to study entry;
• No transfusion of packed red cells within 15 days before enrollment or randomization in the study;
• Participation in another clinical trial;
• Psychiatric pathology can disrupt the course of treatment or prevent the interpretation of results;
• Pregnant or lactating women;
• Persons deprived of liberty;
• Major subject to a measure of legal protection or unable to consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Roche Pharma AG

INDUSTRY

Sponsor Role: collaborator

Vifor Pharma

INDUSTRY

Sponsor Role: collaborator

Centre Francois Baclesse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel SEVIN, MD

Role: PRINCIPAL_INVESTIGATOR

Centre François Baclesse

Locations

CHU

Caen, , France

Centre François Baclesse

Caen, , France

Countries

France

Other Identifiers

FERASE

Identifier Type: -

Identifier Source: org_study_id