Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HMR4396B/3001
Study information
Scientific title
Acronym
Study hypothesis
Advanced cancer is frequently associated with significant anaemia. The causes of this anaemia are multi-factorial and may include the cytotoxic effects of chemotherapeutic agents on bone marrow.
Primary objective was to determine in anaemic cancer subjects treated with chemotherapy, the efficacy of 150 and 300 U/kg of subcutaneously injected HMR4396 compared to placebo based on haemoglobin and the percent of these subjects requiring red blood cell transfusions.
Ethics approval
This was a multi-national, multi-centre trial with 49 centres in the United States. The independent ethics committee from each of the sites approved the study before subjects were enrolled.
Study design
Phase III, randomised, multinational, double-blind, placebo-controlled, parallel arm study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Anaemia
Intervention
The intervention was administration of HMR4396 at a dose of 150 U/kg or 300 U/kg compared to placebo. All study treatments were given three times weekly subcutaneously for 12 weeks.
Quality of life was evaluated using the Functional Assessment of Cancer Therapy - Anaemia (FACT-An) questionnaire.
Intervention type
Drug
Phase
Phase III
Drug names
HMR4396
Primary outcome measure
The co-primary efficacy endpoints in this study were the determination of each subjects change in haemoglobin from baseline to week 12 and the occurrence of red blood cell transfusions during week 5 to 12 (yes/no). The primary analysis was based on the Intent-To Treat (ITT) population.
Secondary outcome measures
Secondary efficacy endpoints were:
1. Change in FACT-An fatigue subscale from baseline to week 12
2. Number of RBC transfusions received during weeks 5 - 12 (expressed as a rate per 28 days)
3. Number of RBC units transfused during weeks 5 - 12 (expressed as a rate per 28 days)
4. Change in Haematocrit (Hct) at week 12 when compared to baseline
5. Average Hgb during weeks 5 - 12
6. Rate of change of Hgb from baseline to first treatment interruption or to when a blood transfusion (red cell or whole blood) was first received
7. Average Hct during weeks 5 - 12
8. Rate of change of Hct from baseline to first treatment interruption or to when a blood transfusion (red cell or whole blood) was first received
9. Change in the total FACT-An score from baseline to week 12
10. Change in each non-fatigue subscale from baseline to week 12
Overall trial start date
18/05/2000
Overall trial end date
20/06/2002
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Men or women, 18 years of age or older, with cancer except for acute leukaemias, malignancies of the myeloid cell line and myelodysplasia
2. Receiving cancer chemotherapy with at least two cycles remaining when randomised to study medication
3. Eastern Cooperative Oncology Group (ECOG) performance score of zero, one or two
4. Life expectancy of three months or greater
5. Haemoglobin (Hgb) less than or equal to 10.5 g/dL
6. Women were to be surgically sterile, post-menopausal (greater than one year) or using an effective method of birth control and were to have had a negative serum pregnancy test (quantitative human chorionic gonadotropin radioimmunoassay test) prior to study medication
7. Men had to agree to an effective method of contraception
8. Laboratory values within the following parameters:
8.1. Neutrophils greater than 500 cells/mm^3 (absolute value = 0.5 x 1000/mm^3 [as per Amendment 1])
8.2. Platelets greater than 75,000 cells/mm^3
8.3. Creatinine less than 2.0 mg/dL
8.4. Serum calcium less than 12 mg/dL
9. Serum ferritin at least 12 mg/mL and transferrin saturation at least 15% as determined by the prestudy evaluation
10. Stool occult blood (negative)
11. A desire and competence to self-administer the study drug or willing to come to the clinic three days each week for the duration of the study to receive study medication
12. Informed consent was obtained for subjects before enrolment in the study
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
575 subjects were screened of which 313 were randomised
Participant exclusion criteria
Subjects meeting any of the following criteria were not to be included in the study:
1. History of any primary non-malignant heamatologic disease
2. Clinically significant disease/dysfunction of the pulmonary, cardiovascular, endocrine, neurological, gastrointestinal, or genitourinary systems not attributable to underlying malignancy and making implementation of the protocol or interpretation of the study results difficult
3. Uncontrolled hypertension (i.e. diastolic Blood Pressure [BP] greater than 100 mmHg) at the prestudy evaluation
4. Evidence of folate or B12 deficiency defined as below the lower standard value for the central laboratory
5. Androgen therapy within two months of randomisation to study medication
6. Known hypersensitivity to erythropoietin
7. Known hypersensitivity to products derived from mammalian cell-culture systems
8. Experimental drug administered or experimental device used within 30 days prior to randomisation to study medication
9. Radiation therapy completed within four weeks before randomisation to study medication or extensive radiation therapy defined as more than 40% of marrow exposed in the radiation field completed within six weeks before randomisation to study medication
10. A malignancy requiring bone marrow transplant or stem cell transplant in the forthcoming 24 weeks (six months)
11. Bone marrow transplant or stem cell transplant recipients
12. Loss of blood requiring Red Blood Cell (RBC) transfusion within the last 30 days
13. Subjects known to be Human Immunodeficiency Virus (HIV) positive
14. Blood (500 ml) or equivalent serum donation during the last three months (as per Amendment 1)
15. Pregnant
16. Breast feeding
17. Treatment with other erythropoietins within the last 12 weeks before randomisation to study medication
18. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol
19. Clinically relevant cardiovascular disease requiring treatment, including but not limited to:
19.1. Myocardial infarction in the preceding six months
19.2. Cardiac arrhythmia
19.3. Unstable angina
20. Current drug abuse
21. Impaired hepatic function, defined as prestudy value for Aspartate Transaminase (AST [SGOT]) or Alanine Transaminase (ALT [SGPT]) exceeding twice the upper limit of normal of the central laboratory values
22. A mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
23. Subjects unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study
Recruitment start date
18/05/2000
Recruitment end date
20/06/2002
Locations
Countries of recruitment
United States of America
Trial participating centre
Shire contact for trial - no PI was identified
Basingstoke
RG24 8EP
United Kingdom
Sponsor information
Organisation
Hoechst Marion Roussel (Shire Pharmaceuticals) (France)
Sponsor details
102 Route de Noisy
Romainville
Cedex
93235
France
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Hoechst Marion Roussel (Shire Pharmaceuticals) (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list