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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

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ClinicalTrials.gov Identifier: NCT02213653
Recruitment Status : Terminated
First Posted : August 11, 2014
Last Update Posted : April 29, 2015
Sponsor:
Collaborators:
Hospira, now a wholly owned subsidiary of Pfizer
Roche Pharma AG
Vifor Pharma
Information provided by (Responsible Party):
Centre Francois Baclesse

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.


Condition or disease Intervention/treatment Phase
Solid Cancer Metastatic Disease Lymphoid Disease Drug: ARM A : IV iron + epoietin zeta Drug: ARM B: IV iron + epoietin zeta sequence Drug: ARM C : single epoietin zeta Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IV 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
Study Start Date : April 2013
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Iron

Arm Intervention/treatment
Experimental: Concomitant iron and I.V. epoietin zeta Drug: 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.

Experimental: Iron and I.V. epoietin zeta sequential 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.

Active Comparator: Epoietin zeta Drug: ARM C : single epoietin zeta
Epoietin zeta at a dose of 450 IU / kg per week subcutaneously begun in week 1




Primary Outcome Measures :
  1. Number of patients with hematopoietic response at 10 weeks. [ Time Frame: The rate of hematopoietic response will be evaluated 10 weeks ]
    The primary objective is to evaluate the rate of hematopoietic response to 10 weeks in patients with anemia and functional iron deficiency treated epoietin zeta + carboxymaltose concomitant IV iron, by epoietin zeta + carboxymaltose IV ferric sequential or epoietin zeta alone


Secondary Outcome Measures :
  1. Number of transfusion requirements [ Time Frame: The number of transfusions will be evaluated weekly Week 1-16 ]
    The secondary objective is to assess transfusion requirements will be evaluated throughout the study


Other Outcome Measures:
  1. The hematopoietic response at 6 and 16 weeks [ Time Frame: The hematopoietic response will be evaluated at 6 and 16 weeks ]
  2. The time to achieve the therapeutic goal (hemoglobin> 12g/dl or increase in hemoglobin> 2g/dl) [ Time Frame: The time to achieve the therapeutic goal will be determine 6,10 and 16 weeks after treatment start ]
  3. Quality of life [ Time Frame: Quality of life will be evaluated 6,10 and 16 weeks after treatment start ]
  4. The consumption of erythropoiesis stimulating agent [ Time Frame: The consumption of erythropoiesis stimulating agent will be evaluated 6,10 and 16 weeks after treatment start ]
  5. The mean increase in hemoglobin concentration [ Time Frame: The mean increase in hemoglobin concentration will be evaluated weekly Week 1-16 ]
  6. The evolution of the iron status parameters [ Time Frame: The evolution of the iron status parameters will be performed at weeks 4,6,10,13 and 16 ]
    Ferritin, CST, soluble transferrin receptor, reticulocytes, CRP will be dosed at weeks 4,6,10,13 and 16

  7. Tolerance [ Time Frame: Tolerance will be evaluated at weeks 6, 10 and 16 ]
  8. Fatigue [ Time Frame: Fatigue will be evaluated 6,10 and 16 weeks after treatment start ]
    Fatigue will be estimated with the generic scale FACT-G



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02213653


Locations
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France
CHU
Caen, France, 14000
Centre François Baclesse
Caen, France, 14076
Sponsors and Collaborators
Centre Francois Baclesse
Hospira, now a wholly owned subsidiary of Pfizer
Roche Pharma AG
Vifor Pharma
Investigators
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Principal Investigator: Emmanuel SEVIN, MD Centre François Baclesse

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Responsible Party: Centre Francois Baclesse
ClinicalTrials.gov Identifier: NCT02213653     History of Changes
Other Study ID Numbers: FERASE
First Posted: August 11, 2014    Key Record Dates
Last Update Posted: April 29, 2015
Last Verified: April 2015
Keywords provided by Centre Francois Baclesse:
Functional iron deficiency
Metastatic
Additional relevant MeSH terms:
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Neoplasm Metastasis
Anemia, Iron-Deficiency
Anemia
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Iron
Central Nervous System Stimulants
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs