Use of Intravenous Ferric Carboxymaltose in Treatment of Anemia in Cancer Patients Undergoing Chemotherapy

Study Overview
=================
Brief Summary
-----------------
This study is a nonrandomized, single arm, open-label study stratified by iron-deficiency status.

Detailed Description
-----------------
The study aims to investigate the effect of FCM (without ESAs) on anemic cancer patients undergoing chemotherapy (with or without radiotherapy); stratified by status of iron deficiency (i.e. non-iron deficient vs. iron deficient patients ). The study will also try to find out whether serum level of Hepcidin and C reactive protein can correlate with response Patients will receive one or two doses of FCM, based on the body weight and Hb level. Patients will be followed-up for a total of twelve weeks. The study is divided into a screening, treatment and follow-up phases and is expected to be completed in 12 months.

Official Title
-----------------
The Use of Intravenous Ferric Carboxymaltose (FCM) Without Erythropoiesis-stimulating Agents (ESA) in the Treatment of Anemia in Cancer Patients Undergoing Chemotherapy With or Without Radiotherapy

Conditions
-----------------
Anemia, Cancer

Intervention / Treatment
-----------------
* Drug: Ferric carboxymaltose (FCM)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is an adult more than or equal 18 years old at the time of informed consent. Patient has pathologic diagnosis of solid tumor (breast cancer, colorectal, lung, sarcoma, head and neck, sarcoma, genitourinary or gynecological cancer). Patients who started chemotherapy (with or without radiotherapy) or planned to receive chemotherapy for at least 12 weeks. Patient has an Eastern Cooperative Oncology Group performance status between 0 and 2. Patient with Hb ≤11 g/dL. Patient has a Life expectancy at least 6 months. Adequate hepatic and renal function defined as a serum aspartate aminotransferase or alanine aminotransferase level that are no more than 3 times the upper limit of the normal range, a serum bilirubin level that is no more than 2 times the upper limit of the normal range and a serum Creatinine level of less than 2 mg per deciliter. Patient is able to understand and provide informed consent to participate in the study. Exclusion Criteria: Patient has Hb < 8.0 g/dL Patient presenting with hematologic malignancy including Prior gastric surgery. Patients on definitive radiotherapy alone. Patients with relevant history (within six weeks) or clinical evidence of hemolysis or active bleeding that could, in the investigator's judgment, be a potential cause for the anemia (no gross hematuria, hemoptysis, hematochezia or melena and negative stool for hemoccult) Presence of other nutritional anemia; deficiency of vitamin B12 less than 187 pg/ml and deficiency of Folate less than 3.1 ng/ml according to the local laboratory normal ranges Patient has Iron overload (Serum Ferritin more than 800 ng/ml or Transferrin saturation (TSAT) more than 40%) Patient is pregnant or lactating. Patient has a personal or family history of hemochromatosis. Patient has hypersensitivity to any form of IV iron. Patient has received red blood cells transfusion or used erythropoietin within 2 weeks of enrollment into the study. Patient has received any form of intravenous iron within the last 12 weeks Patient has received oral iron supplements within 1 month of enrollment to the study, except for multivitamin supplements containing less than 30 mg iron.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This study is a nonrandomized, single arm, open-label study stratified by iron-deficiency status.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferric carboxymaltose (ferrinject)<br>Patients will receive one or two doses of Ferric carboxymaltose (ferrinject), based on the body weight and Hb level. Ferric carboxymaltose will be administered as a single infusion if the needed dose is 1000 mg as a short IV infusion If the needed Ferric carboxymaltose dose is > 1000 mg, an initial dose of 1000 mg will be given as a short IV infusion and the remaining dose will be given the week after in a similar fashion | Drug: Ferric carboxymaltose (FCM)<br>* intravenous iron formulation<br>* Other names: Ferinject;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Median Hb Change From Baseline to Week 12 | The median Hb change from baseline to week 12 per patient in the three groups, Based on serum ferritin (sFr) and transferrin saturation(TSAT), patients were divided into the 3 groups: group I (absolute iron deficiency, n = 26) with sFr < 30 ng/mL and TSAT < 20%; group II (functional iron deficiency, n = 24) with sFr 30-800 ng/mL and TSAT < 20%; and patients with TSAT ⩾ 20% were placed in group III as others (n = 34). | up to 12 weeks | 
| Percentage of Patients With Hb Increment of at Least 1.0 gm/dL. | Percentage of patients with Hb increment of at least 1.0 gm/dL during their participation (from baseline to week 12 per patient) in the three groups, Based on serum ferritin (sFr) and transferrin saturation(TSAT), patients were divided into the 3 groups: group I (absolute iron deficiency, n = 26) with sFr < 30 ng/mL and TSAT < 20%; group II (functional iron deficiency, n = 24) with sFr 30-800 ng/mL and TSAT < 20%; and patients with TSAT ⩾ 20% were placed in group III as others (n = 34). | up to 12 weeks | 
| Percentage of Patients Achieving Correction of Anemia (Hb >11.0 gm/dL) | Percentage of patients achieving correction of anemia (Hb >11.0 gm/dL) during their participation (from baseline to week 12 per patient) in the three groups. A total of 84 adult cancer patients on active chemotherapy with hemoglobin (Hb) level ⩽11.0 g/dL were recruited. Based on serum ferritin (sFr) and transferrin saturation(TSAT), patients were divided into 3 groups: group I (absolute iron deficiency, n = 26) with sFr < 30 ng/mL and TSAT < 20%; group II (functional iron deficiency, n = 24) with sFr 30-800 ng/mL and TSAT < 20%; and patients with TSAT ⩾ 20% were placed in group III as others (n = 34). | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate in Relation to Baseline Iron Deficiency Status | Response rate in relation to baseline iron deficiency status; Patients were considered responders if they showed a minimum of 1.0 gm/dL increment in Hb level during their participation (from baseline to week 12 per patient) Based on serum ferritin (sFr) and transferrin saturation(TSAT), patients were divided into 3 groups: group I (absolute iron deficiency, n = 26) with sFr < 30 ng/mL and TSAT < 20%; group II (functional iron deficiency, n = 24) with sFr 30-800 ng/mL and TSAT < 20%; and patients with TSAT ⩾ 20% were placed in group III as others (n = 34). | up to 12 weeks | 
| Percentage of Patients Who Will Require Blood Transfusion or ESA Treatment | Percentage of patients who received red blood cells (RBCs) transfusion or used erythropoietin during their participation (from baseline to week 12 per patient) among the 84 recruited adult cancer patients on active chemotherapy with hemoglobin (Hb) level ⩽11.0 g/dL | up to 12 weeks |