Erythropoietin and Iron Supplementation for Patients With Chemotherapy-induced Anaemia

October 28, 2016 updated by: Chen Lin, Shanghai East Hospital

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

603

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lin Chen, Master
  • Phone Number: 17216 8621-38804518
  • Email: 896571345@qq.com

Study Contact Backup

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China
        • Shanghai East Hospital Home Branch
        • Contact:
      • Shanghai, Shanghai, China
        • Shanghai East Hospital South Branch
        • Contact:
      • Shanghai, Shanghai, China
        • Shanghai First People's Hospital
        • Contact:
      • Shanghai, Shanghai, China
        • Shanghai Sixth People's Hospital Lingang Branch
        • Contact:
      • Shanghai, Shanghai, China
        • The First Affiliated Hospital, The Second Military Medical University
        • Contact:
    • Zhejiang
      • Jian, Zhejiang, China
        • Shanghai East Hospital Jian Branch
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EPO plus sustained iron dextran
Group 1, EPO treatment at the original dose plus IV iron dextran 200 mg every three weeks (Q3W) for 15 weeks
Drug: Erythropoietins (EPO)
A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections.
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
Experimental: EPO plus aggressive iron dextran
Group 2, EPO treatment at the original dose plus IV iron dextran 100 mg, twice a week (BIW) for five weeks
Drug: Erythropoietins (EPO)
A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections.
Drug: Erythropoietins (EPO)
Doubling EPO dosage to 20,000 IU, three times weekly by subcutaneous injections with a maximum of 5 doses
Drug: Aggressive iron dextran supplementation
Iron dextran 100 mg, BIW, through 90 minutes of IV infusion, for the first consecutive 5 weeks
Active Comparator: Double EPO
Group 3, the control group, doubling the EPO dose without preplanned iron supplementation
Drug: Erythropoietins (EPO)
A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections.
Drug: Erythropoietins (EPO)
Doubling EPO dosage to 20,000 IU, three times weekly by subcutaneous injections with a maximum of 5 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hb response rate
Time Frame: up to week 15
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

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportions of patients requiring therapeutic blood transfusions
Time Frame: Within 15 weeks
Within 15 weeks
Time-to-progression (TTP)
Time Frame: Baseline, week 15, and then once per 3 months in the first year and once per 6 months thereafter up to 2 years
Baseline, week 15, and then once per 3 months in the first year and once per 6 months thereafter up to 2 years
Volume of transfused blood
Time Frame: Within 15 weeks
Within 15 weeks

Other Outcome Measures

Outcome Measure
Time Frame
Adverse events (AEs)
Time Frame: Through study completion, up to 2 years
Through study completion, up to 2 years
Quality of life - Linear Analogue Self-Assessment test
Time Frame: Baseline and week 3, 6, 9, 12 and 15
Baseline and week 3, 6, 9, 12 and 15
Quality of life - Functional Assessment of Cancer Therapy-Anaemia test
Time Frame: Baseline and week 3, 6, 9, 12 and 15
Baseline and week 3, 6, 9, 12 and 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai East Hospital

Investigators

  • Principal Investigator: Yong Gao, PhD, Shanghai East Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2016

Primary Completion (Anticipated)

April 1, 2019

Study Completion (Anticipated)

November 1, 2019

Study Registration Dates

First Submitted

March 16, 2016

First Submitted That Met QC Criteria

April 6, 2016

First Posted (Estimate)

April 7, 2016

Study Record Updates

Last Update Posted (Estimate)

November 1, 2016

Last Update Submitted That Met QC Criteria

October 28, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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