A Safety Study of Epoetin Alfa in Patients With Cancer Who Have Chemotherapy-Related Anemia

• ClinicalTrials.gov Identifier: NCT01394991
• Recruitment Status: Completed
• First Posted: July 15, 2011
• Results First Posted: July 15, 2011
• Last Update Posted: April 5, 2012
• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
• Information provided by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study Description

Brief Summary:

The purpose of the study is to evaluate the safety of epoetin alfa in patients with cancer who have chemotherapy-related anemia.

Condition or disease	Intervention/treatment	Phase
Anemia; Neoplasms	Drug: Epoetin alfa 450 IU/kg once a week; Drug: Epoetin alfa 150 IU/kg 3 times a week; Drug: Epoetin alfa 450 IU/kg once a week (QW); Drug: Epoetin alfa 150 IU/kg 3 times a week (TIW)	Phase 4

Detailed Description:

Epoetin alfa is an agent similar to a hormone produced in the kidney (ie, erythropoietin) that functions to increase the amount of red blood cells made in the bone marrow. This is a randomized (study drug assigned by chance), open-label (patients and their doctors will know the identity of study drug administered), safety study of 2 dosing regimens (doses and schedules) of epoetin alfa administered to patients with cancer who have chemotherapy-related anemia. Anemia is a lack of red blood cells that can result in symptoms of weakness, shortness of breath, fatigue, tiredness, and decreased activity. The primary outcome measure in the study is the number of patients in each treatment group with at least 1 clinically relevant and objectively confirmed (adjudicated) thrombovascular event (TVE) reviewed by an independent adjudication committee from Day 1 (baseline or the day of the first dose) through Week 16. An external review of relevant clinical data and medical imaging studies by an Adjudication Committee will be performed in a blinded fashion for confirmation of TVEs. The Adjudication Committee will confirm TVEs by reviewing all images (X-ray, Computed tomography [CT] scan, ultrasound, Magnetic Resonance Imaging [MRI] scan, etc) and other diagnostic procedures auch as coagulation tests or electrocardiograms in combination with a clinical patient profile as described for each specific type of TVE. Only TVEs that are determined by the Adjudication Committee to be clinically relevant and objectively confirmed will be counted in the analysis for the primary endpoint. Approximately 500 patients, who have cancer, are receiving chemotherapy, and are anemic, will take part in the study. Patients will participate in the study for up to 32 weeks (this includes a 2-week screening period to determine eligibility for the study, a 26-week treatment period, and a 4-week follow-up period to have end-of-study assessments [tests] performed). The length of participation in the study depends on the length of time the patient is receiving chemotherapy and epoetin alfa; patients in the study may receive up to a maximum of 26 weeks of treatment with epoetin alfa. Patients will be randomly assigned (assigned by chance like flipping a coin) to 1 of 2 treatment groups (Epoetin Alfa QW or Epoetin Alfa TIW). Patients assigned to the Epoetin Alfa QW Group will receive epoetin alfa at an initial dosage of 450 IU/kg once a week and patients assigned to Epoetin Alfa TIW Group will receive epoetin alfa 150 IU/kg 3 times a week by subcutaneous (underneath the skin) injection. Injections will be given preferably on Monday for patients in the Epoetin Alfa QW Group and on Mondays, Wednesdays, and Fridays for patients in the Epoetin Alfa TIW Group. During the study, patients will visit the study center weekly to have a blood sample collected to measure the amount of hemoglobin (red blood cells) in the blood. Depending on the hemoglobin level, the dose of epoetin alfa may be increased or decreased. Regardless of treatment group, if anemia does not improve in patients after 4 weeks of treatment, the dose of epoetin alfa will be increased to 300 IU/kg 3 times a week. If anemia does not improve after 4 weeks at the increased dose level of epoetin alfa (300 IU/kg 3 times a week), treatment with epoetin alfa will be stopped. In addition, during the study, patients may also receive treatment with iron supplements if the level of iron in the blood is low. During the study, safety will be monitored by evaluating adverse events and findings from clinical laboratory tests, 12-lead electrocardiograms (ECGs), blood pressure measurements, and physical examinations. Patients will receive epoetin alfa at an initial dose of 450 IU/kg once a week or 150 IU/kg 3 times a week by subcutaneous injection, preferably in the abdomen, for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks. Injections for Epoetin Alfa QW Group will be at the study center and for Epoetin TIW Group, the 1st weekly injection will be at the study center and the 2nd and 3rd weekly injections will be at the study center or at home by self-administration.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 504 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Multicenter Study Evaluating Thrombovascular Events in Subjects With Cancer Receiving Chemotherapy and Administered Epoetin Alfa Once or Three Times a Week for the Treatment of Anemia
• Study Start Date: January 2006
• Actual Primary Completion Date: September 2009
• Actual Study Completion Date: September 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: 001; Epoetin alfa 450 IU/kg once a week (QW) 450 IU/kg once a week (QW) by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks	Drug: Epoetin alfa 450 IU/kg once a week; 450 IU/kg once a week by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks.; Drug: Epoetin alfa 450 IU/kg once a week (QW); 450 IU/kg once a week (QW) by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks
Experimental: 002; Epoetin alfa 150 IU/kg 3 times a week (TIW) 150 IU/kg 3 times a week (TIW) by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks.	Drug: Epoetin alfa 150 IU/kg 3 times a week; 150 IU/kg 3 times a week by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks.; Drug: Epoetin alfa 150 IU/kg 3 times a week (TIW); 150 IU/kg 3 times a week (TIW) by subcutaneous injection preferably in the abdomen for up to 4 weeks after the last dose of chemotherapy for a maximum of 26 weeks.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With at Least 1 Clinically Relevant and Objectively Confirmed Thrombovascular Event From Randomization Through Week 16 [ Time Frame: from randomization through Week 16 ]
   Clinically relevant and objectively confirmed thrombovascular event (TVE) was determined by the Adjudication Committee from randomization through Week 16. Clinically relevant TVEs were defined as deep vein thrombosis (DVT) of the limbs; thromboses of other major veins; pulmonary embolism (PE);acute coronary syndrome (ACS);ischemic stroke of arterial or cardiac origin; cerebral venous thrombosis; and arterial thrombosis. Objectively confirmed was defined as the confirmation of the clinical diagnosis of a TVE by appropriate medical imaging studies and laboratory tests.

Secondary Outcome Measures :

1. Number of Positively Adjudicated Thrombovascular Events [ Time Frame: during the study (randomization through week 26) ]
   The number of participants who have at least 1 clinically relevant and objectively confirmed (adjudicated) thrombovascular event (TVE) during the study.
2. Time to First Positively Adjudicated Thrombovascular Event [ Time Frame: during the study (randomization through week 26) ]
   Analysis of time to first positively adjudicated thrombovascular event (TVE) measured from the date of randomization to the date of the first clinically relevant and objectively confirmed TVE as determined by the Adjudication Committee. Median time is non-estimable because of too few events, incidence was reported instead.
3. Number of Suspected Thrombovascular Events [ Time Frame: during the study (randomization through week 26) ]
   Number of participants who have at least 1 suspected thrombovascular events (TVEs) during the entire study. Suspected TVEs were defined as suspected TVEs during the entire study, whether clinically relevant and objectively confirmed by the Adjudication Committee or not, whether confirmed by the investigator or not.
4. Time to First Suspected Thrombovascular Event [ Time Frame: during the study (randomization through week 26) ]
   Analysis of time to first suspected thrombovascular event (TVE) measured from the date of randomization to the date of the first suspected TVE during the study. Median time is non-estimable because of too few events, incidence was reported instead.
5. Mortality [ Time Frame: during the study (randomization through week 26) ]
   Number of participants who died during the study.
6. Number of Hemoglobin Responders [ Time Frame: during the study (randomization through week 26) ]
   Hemoglobin response was defined as a hemoglobin increase of ≥2 g/dL from baseline or reaching a hemoglobin concentration of 12 g/dL, regardless of dose adjustment.
7. Red Blood Cell Transfusions [ Time Frame: during the study (randomization through week 26) ]
   The number of participants who received at least 1 red blood cell (RBC) transfusion (packed RBC or whole blood) during the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Any nonmyeloid tumor confirmed by cytology and/or histology
• Day 1 baseline hemoglobin (Hb) level <=11 g/dL
• Expected to receive at least 12 weeks of chemotherapy after enrollment into the study
• Eastern Cooperative Oncology Group (ECOG) performance status <= 2

Exclusion Criteria:

• History of active second cancer except for adequately treated skin cancer and in situ (pre-invasive) cervical cancer
• History of deep venous thrombosis (DVT) (blood clots in the veins of the thighs or legs) or pulmonary embolism (PE) (blood clot in the lungs) within 12 months before study entry or at any time if the event is related to the current cancer, which is defined as diagnosis of the cancer within 3 months of a DVT/PE episode or a DVT/PE following the cancer diagnosis/treatment
• History of cardiovascular accident (CVA), transient ischemic attack (TIA) (stroke), acute coronary syndrome (ACS) (a condition indicating damage to the heart), or other arterial thrombosis (blood clots) within 6 months before study entry
• Onset of seizures within 3 months before randomization or poorly controlled seizures
• Brain tumor or brain metastasis from another malignancy or cardiac disease that is markedly or completely limiting, uncontrolled hypertension (high blood pressure), or anemia (a lack of red blood cells in the blood) for reasons other than cancer or chemotherapy
• Specifically excluded concomitant medications or therapies including prophylactic anticoagulation therapy for recurrence of prior thrombovascular event (TVE) (warfarin, unfractionated heparin, low molecular weight heparin [LMWH], except for prevention of central venous catheter thrombosis at doses specified in the protocol, direct thrombin inhibitors, or anti-platelet drugs [e.g., clopidogrel or ticlopidine]), except for prophylaxis in patients with known cardiovascular disease

Contacts and Locations

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

• Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

More Information

• Responsible Party: Senior Director, CDTL PROCRIT/EPREX, Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
• ClinicalTrials.gov Identifier: NCT01394991
• Other Study ID Numbers: CR010543; EPOANE4008
• First Posted: July 15, 2011
• Results First Posted: July 15, 2011
• Last Update Posted: April 5, 2012
• Last Verified: April 2012

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Epoetin alfa (EPREX, ERYPO)

Additional relevant MeSH terms:

Anemia; Hematologic Diseases; Epoetin Alfa; Hematinics