Clinical trial NCT02731378: Erythropoietin and Iron Supplementation for Patients With Chemotherapy-induced Anaemia
Official title: Combination With Intravenous Iron Supplementation or Doubling Erythropoietin Dose for Patients With Chemotherapy-induced Anaemia Inadequately Responsive to Initial Erythropoietin Treatment Alone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chemotherapy-induced Anaemia
Keywords: erythropoietin
iron supplementation
inadequately responsive
chemotherapy-induced anaemia
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2016-04-07
Enrollment: 603
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older;
* Had histologically, cytologically or clinically diagnosed malignant tumour and measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1;
* Undergoing adjuvant or palliative chemotherapy with an expected survival of at least 3 months;
* Inadequately responsive or unresponsive to routine dosages of EPO treatment. Inadequate responders or nonresponders are defined as those CIA patients with an increase of Hb \< 1g/dL after 4 weeks of treatment with 10, 000 IU of EPO, three times weekly by subcutaneous injection).
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2;
* Are compliant and can understand the research and sign an informed consent form.

Exclusion Criteria:

* History of thromboembolism in the previous twelve months;
* Family history of hemochromatosis;
* Anaemia diagnosed with myelodysplastic syndrome or hematologic diseases such as Mediterranean anaemia;
* Received EPO treatment in the prior three months;
* Received erythrocyte suspension transfusion in the prior two weeks;
* Women who are pregnant or lactating;
* Have a history of hypertension or mental illness.

Primary outcomes:
measure: Hb response rate
timeFrame: up to week 15
Secondary outcomes:
measure: Proportions of patients requiring therapeutic blood transfusions
timeFrame: Within 15 weeks
measure: Time-to-progression (TTP)
timeFrame: Baseline, week 15, and then once per 3 months in the first year and once per 6 months thereafter up to 2 years
measure: Volume of transfused blood
timeFrame: Within 15 weeks
Other outcomes:
measure: Adverse events (AEs)
timeFrame: Through study completion, up to 2 years
measure: Quality of life - Linear Analogue Self-Assessment test
timeFrame: Baseline and week 3, 6, 9, 12 and 15
measure: Quality of life - Functional Assessment of Cancer Therapy-Anaemia test
timeFrame: Baseline and week 3, 6, 9, 12 and 15
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital Home Branch
state: Shanghai
city: Shanghai
country: China
facility: Shanghai East Hospital South Branch
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First People's Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Lingang Branch
state: Shanghai
city: Shanghai
country: China
facility: The First Affiliated Hospital, The Second Military Medical University
state: Shanghai
city: Jian
country: China
facility: Shanghai East Hospital Jian Branch
state: Zhejiang
Study officials:
affiliation: Shanghai East Hospital
name: Yong Gao, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen L, Jiang H, Gao W, Tu Y, Zhou Y, Li X, Zhu Z, Jiang Q, Zhan H, Yu J, Fu C, Gao Y. Combination with intravenous iron supplementation or doubling erythropoietin dose for patients with chemotherapy-induced anaemia inadequately responsive to initial erythropoietin treatment alone: study protocol for a randomised controlled trial. BMJ Open. 2016 Oct 7;6(10):e012231. doi: 10.1136/bmjopen-2016-012231.