Chemotherapy-induced AnaemiaPhase 4NCT02731378
Erythropoietin and Iron Supplementation for Patients With Chemotherapy-induced Anaemia
A Phase 4 study testing Erythropoietins (EPO), Aggressive iron dextran supplementation and Sustained iron dextran supplementation in people with Chemotherapy-induced Anaemia, run by Shanghai East Hospital at 6 sites in China.
Trial summary
A multicentre, randomized, open-label, parallel-group, active controlled non-inferiority study Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chemotherapy-induced Anaemia
- What is being tested?
- Erythropoietins (EPO), Aggressive iron dextran supplementation and Sustained iron dextran supplementation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 603 participants
- Where
- 6 sitesChina
- Study dates
- Dec 2016to Nov 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
China6 sites
Shanghai East Hospital Jian Branch
Jian, Zhejiang
Ying Zhou, 0796-8311066, yjm_st@163.com
Shanghai East Hospital Home Branch
Shanghai, Shanghai Municipality
Hong Jiang, 021-38804518-17216, jianghong2046@126.com
Shanghai East Hospital South Branch
Shanghai, Shanghai Municipality
Yong Gao, PhD, 021-38804518, drgaoyong@163.com
Shanghai First People's Hospital
Shanghai, Shanghai Municipality
Qi Li, 021-63240090, yoursgaowei@163.com
Shanghai Sixth People's Hospital Lingang Branch
Shanghai, Shanghai Municipality
Daliu Min, 021-64369181, dan16065@163.com
The First Affiliated Hospital, The Second Military Medical University
Shanghai, Shanghai Municipality
Chuangang Fu, 021-31166666, fugang416@126.com
About this study
Official title: 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
Read the 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
- Being tested
- Erythropoietins (EPO), Aggressive iron dextran supplementation, Sustained iron dextran supplementation
- Keywords
- erythropoietin, iron supplementation, inadequately responsive, chemotherapy-induced anaemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erythropoietins (EPO)Drug
A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections.
Aggressive iron dextran supplementationDrug
Iron dextran 100 mg, BIW, through 90 minutes of IV infusion, for the first consecutive 5 weeks
Erythropoietins (EPO)Drug
Doubling EPO dosage to 20,000 IU, three times weekly by subcutaneous injections with a maximum of 5 doses
Sustained iron dextran supplementationDrug
Iron dextran 200 mg, Q3W, through 90 minutes of IV infusion and a maximum of 5 doses
| Study group | Role | What they receive |
|---|---|---|
| EPO plus sustained iron dextran | Experimental | Group 1, EPO treatment at the original dose plus IV iron dextran 200 mg every three weeks (Q3W) for 15 weeks Receives: Drug: Erythropoietins (EPO); Drug: Sustained iron dextran supplementation |
| EPO plus aggressive iron dextran | Experimental | Group 2, EPO treatment at the original dose plus IV iron dextran 100 mg, twice a week (BIW) for five weeks Receives: Drug: Erythropoietins (EPO); Drug: Aggressive iron dextran supplementation |
| Double EPO | Active comparator | Group 3, the control group, doubling the EPO dose without preplanned iron supplementation Receives: Drug: Erythropoietins (EPO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to week 15
Secondary outcomes (3)
Proportions of patients requiring therapeutic blood transfusions
Measured: Within 15 weeks
Time-to-progression (TTP)
Measured: 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
Measured: Within 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2016 (estimated)
- Study startDec 2016
- Primary completionApr 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy-induced AnaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 603 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai East Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chen Lin, Shanghai East Hospital
- Investigators
- Yong Gao, PhD, Principal investigator, Shanghai East Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02731378
- Sponsor's protocol ID
- 2016003
- Status last verified
- Oct 2016
- First submitted
- 16 Mar 2016
- Last updated
- 1 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 27855097
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination With Intravenous Iron Supplementation or Doubling Erythropoietin Dose for Patients With Chemotherapy-induced Anaemia Inadequately Responsive to Initial Erythropoietin Treatment Alone
- ClinicalTrials.gov ID
- NCT02731378
- Acronym / sponsor ID
- 2016003
- Conditions
- Chemotherapy-induced Anaemia
- Keywords
- erythropoietin, iron supplementation, inadequately responsive, chemotherapy-induced anaemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 603 participants (estimated)
- Lead sponsor
- Shanghai East HospitalUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 7 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EPO plus sustained iron dextran | Experimental | Drug: Erythropoietins (EPO), Drug: Sustained iron dextran supplementationGroup 1, EPO treatment at the original dose plus IV iron dextran 200 mg every three weeks (Q3W) for 15 weeks |
| EPO plus aggressive iron dextran | Experimental | Drug: Erythropoietins (EPO), Drug: Aggressive iron dextran supplementationGroup 2, EPO treatment at the original dose plus IV iron dextran 100 mg, twice a week (BIW) for five weeks |
| Double EPO | Active comparator | Drug: Erythropoietins (EPO)Group 3, the control group, doubling the EPO dose without preplanned iron supplementation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Erythropoietins (EPO)A routine dose 10,000 IU of EPO, three times weekly by subcutaneous injections. | Drug | EPO plus aggressive iron dextran, EPO plus sustained iron dextran |
| Aggressive iron dextran supplementationIron dextran 100 mg, BIW, through 90 minutes of IV infusion, for the first consecutive 5 weeks | Drug | EPO plus aggressive iron dextran |
| Erythropoietins (EPO)Doubling EPO dosage to 20,000 IU, three times weekly by subcutaneous injections with a maximum of 5 doses | Drug | Double EPO |
| Sustained iron dextran supplementationIron dextran 200 mg, Q3W, through 90 minutes of IV infusion and a maximum of 5 doses | Drug | EPO plus sustained iron dextran |
Primary outcome
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.
3 secondary outcomes
Proportions of patients requiring therapeutic blood transfusions
Time frame: 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
Volume of transfused blood
Time frame: Within 15 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2016.
- Derived from this study: PubMed 27855097Chen 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yong Gao, PhD principal investigator
Shanghai East Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Erythropoietins (EPO), Aggressive iron dextran supplementation and Sustained iron dextran supplementation in people with Chemotherapy-induced Anaemia, run by Shanghai East Hospital at 6 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lin Chen, Master (8621-38804518 ext. 17216, 896571345@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hb response rate (time frame: up to week 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02731378, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2016.