Erythropoietin and Iron Supplementation for Patients With Chemotherapy-induced Anaemia

Chemotherapy-induced Anaemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02731378
• Other study ID #: 2016003
• Status: Not yet recruiting
• Phase: Phase 4
• First received: March 16, 2016
• Last updated: October 28, 2016
• Start date: December 2016
• Est. completion date: November 2019

Study information

• Verified date: October 2016
• Source: Shanghai East Hospital
• Contact: Lin Chen, Master
• Phone: 8621-38804518
• Email: 896571345[@]qq.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 603
• Est. completion date: November 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Chemotherapy-induced Anaemia

Intervention

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

Locations

Country	Name	City	State
China	Shanghai East Hospital Jian Branch	Jian	Zhejiang
China	Shanghai East Hospital Home Branch	Shanghai	Shanghai
China	Shanghai East Hospital South Branch	Shanghai	Shanghai
China	Shanghai First People's Hospital	Shanghai	Shanghai
China	Shanghai Sixth People's Hospital Lingang Branch	Shanghai	Shanghai
China	The First Affiliated Hospital, The Second Military Medical University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai East Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events (AEs)		Through study completion, up to 2 years	Yes
Other	Quality of life - Linear Analogue Self-Assessment test		Baseline and week 3, 6, 9, 12 and 15	No
Other	Quality of life - Functional Assessment of Cancer Therapy-Anaemia test		Baseline and week 3, 6, 9, 12 and 15	No
Primary	Hb response rate	A CIA patient would be defined as an Hb responder to study treatment if either Hb concentration of this patient is at least 12 g/dL or there is an increase in Hb levels of more than 2-g/dL compared to baseline level without blood transfusions initiated in the previous 28 days.	up to week 15	No
Secondary	Proportions of patients requiring therapeutic blood transfusions		Within 15 weeks	No
Secondary	Time-to-progression (TTP)		Baseline, week 15, and then once per 3 months in the first year and once per 6 months thereafter up to 2 years	Yes
Secondary	Volume of transfused blood		Within 15 weeks	No