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
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02213653|
Recruitment Status : Terminated
First Posted : August 11, 2014
Last Update Posted : April 29, 2015
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|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Experimental: Concomitant iron and I.V. epoietin zeta||
Drug: ARM A : IV iron + epoietin zeta
|Experimental: Iron and I.V. epoietin zeta sequential||
Drug: ARM B: IV iron + epoietin zeta sequence
|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
- 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
- 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
- The hematopoietic response at 6 and 16 weeks [ Time Frame: The hematopoietic response will be evaluated at 6 and 16 weeks ]
- 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 ]
- Quality of life [ Time Frame: Quality of life will be evaluated 6,10 and 16 weeks after treatment start ]
- 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 ]
- The mean increase in hemoglobin concentration [ Time Frame: The mean increase in hemoglobin concentration will be evaluated weekly Week 1-16 ]
- 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
- Tolerance [ Time Frame: Tolerance will be evaluated at weeks 6, 10 and 16 ]
- 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
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
|Caen, France, 14000|
|Centre François Baclesse|
|Caen, France, 14076|
|Principal Investigator:||Emmanuel SEVIN, MD||Centre François Baclesse|