NCT02731378

Erythropoietin and Iron Supplementation for Patients With Chemotherapy-induced Anaemia

Combination With Intravenous Iron Supplementation or Doubling Erythropoietin Dose for Patients With Chemotherapy-induced Anaemia Inadequately Responsive to Initial Erythropoietin Treatment Alone

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 603 (estimated)
• Sponsor: Shanghai East Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A multicentre, randomized, open-label, parallel-group, active controlled non-inferiority study

Detailed description

Chemotherapy-induced anaemia (CIA) is a significant health problem for patients with cancer undergoing chemotherapy, causing fatigue and reducing quality of life (QoL). Up to 75% of cancer patients undergoing chemotherapy and/or radiotherapy reportedly experience mild-to-moderate anaemia (defined by a haemoglobin level of 9 to 11 g/dL). In clinical trials, erythropoietins (EPOs) have been shown to increase haemoglobin levels and improve anaemia and QoL in cancer patients. However, recent meta-analyses have highlighted possible safety issues regarding EPO exposure. Preclinical studies have pointed towards the role of EPO in augmenting tumorigenesis, metastasis, risk of thrombosis, and drug resistance in certain tumor types (e.g., breast cancer), as it can activate important antiapoptotic pathways targeted by current antineoplastic therapies, thus counteracting their effects. Current guidelines in western countries and China recommend restricted usage of EPOs and reduction / prevention of blood transfusions in the treatment of cancer-induced anaemia. However, the inadequate response to erythropoietic therapy has not been well-characterized through rigorous studies and hence remains poorly handled in routine clinical practice. A major cause for not responding to EPO treatment is likely functional iron deficiency (FID), which is defined as a failure to provide iron to the erythroblasts despite sufficient iron stores. Patients with FID require supplementation of usable iron to optimize response to erythropoietic therapy, which might not be accomplished with oral iron. In a recent prospective, open-label trial, patients receiving epoetin alfa for CIA who were treated with IV iron dextran had a significantly greater Hb response compared with those receiving oral iron. Meanwhile, in patients with CIA and no iron deficiency, IV iron supplementation significantly reduced treatment failures to darbepoetin without additional toxicity. However, whether that IV iron supplementation increases the risk of disease progression, incidence of thrombosis and heart failure as well as iron overload, is under careful investigation. Though the association between IV iron and serious AEs and mortality remains unclear, Zitt et al. found that the use of IV iron was associated with a 22% reduction in mortality. Therefore, investigators designed this multicentre, randomized trial to investigate EPOs in combination with IV iron with regard to an increase of Hb levels in patients who have inadequate responses to initial treatment with routine doses of EPOs.

Conditions

• Chemotherapy-induced Anaemia

Interventions

Type	Name	Description
DRUG	Erythropoietins (EPO)	A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections.
DRUG	Aggressive iron dextran supplementation	Iron dextran 100 mg, BIW, through 90 minutes of IV infusion, for the first consecutive 5 weeks
DRUG	Erythropoietins (EPO)	Doubling EPO dosage to 20,000 IU, three times weekly by subcutaneous injections with a maximum of 5 doses
DRUG	Sustained iron dextran supplementation	Iron dextran 200 mg, Q3W, through 90 minutes of IV infusion and a maximum of 5 doses

Timeline

• Start date: 2016-12-01
• Primary completion: 2019-04-01
• Completion: 2019-11-01
• First posted: 2016-04-07
• Last updated: 2016-11-01

Locations

6 sites across 1 country: China