Trial Outcomes & Findings for A Safety Study of Epoetin Alfa in Patients With Cancer Who Have Chemotherapy-Related Anemia (NCT NCT01394991)
NCT ID: NCT01394991
Last Updated: 2012-04-05
Results Overview
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.
COMPLETED
PHASE4
504 participants
from randomization through Week 16
2012-04-05
Participant Flow
This is a randomized, open-label, multicenter study evaluating thrombovascular events in participants with cancer receiving chemotherapy and administered Epoetin Alfa once weekly (QW) or three times a week (TIW) for the treatment of anemia.
Participant milestones
| Measure |
Epoetin Alfa QW
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Overall Study
STARTED
|
242
|
262
|
|
Overall Study
COMPLETED
|
183
|
190
|
|
Overall Study
NOT COMPLETED
|
59
|
72
|
Reasons for withdrawal
| Measure |
Epoetin Alfa QW
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
4
|
|
Overall Study
Lack of Efficacy
|
5
|
7
|
|
Overall Study
Lost to Follow-up
|
6
|
8
|
|
Overall Study
Physician Decision
|
1
|
3
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
20
|
17
|
|
Overall Study
Chemotherapy Termination
|
10
|
15
|
|
Overall Study
Disease Progression
|
7
|
7
|
|
Overall Study
Prematurely Termination of Trial
|
9
|
10
|
Baseline Characteristics
A Safety Study of Epoetin Alfa in Patients With Cancer Who Have Chemotherapy-Related Anemia
Baseline characteristics by cohort
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
Total
n=504 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
160 Participants
n=5 Participants
|
173 Participants
n=7 Participants
|
333 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
81 Participants
n=5 Participants
|
88 Participants
n=7 Participants
|
169 Participants
n=5 Participants
|
|
Age Continuous
|
58.8 years
STANDARD_DEVIATION 13.35 • n=5 Participants
|
57.5 years
STANDARD_DEVIATION 13.53 • n=7 Participants
|
58.1 years
STANDARD_DEVIATION 13.44 • n=5 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=5 Participants
|
181 Participants
n=7 Participants
|
337 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
86 Participants
n=5 Participants
|
81 Participants
n=7 Participants
|
167 Participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
6 participants
n=5 Participants
|
7 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
France
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
51 participants
n=5 Participants
|
55 participants
n=7 Participants
|
106 participants
n=5 Participants
|
|
Region of Enrollment
Great Britain
|
1 participants
n=5 Participants
|
4 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
8 participants
n=5 Participants
|
12 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
21 participants
n=5 Participants
|
20 participants
n=7 Participants
|
41 participants
n=5 Participants
|
|
Region of Enrollment
Russia
|
88 participants
n=5 Participants
|
93 participants
n=7 Participants
|
181 participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
9 participants
n=5 Participants
|
11 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
31 participants
n=5 Participants
|
35 participants
n=7 Participants
|
66 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: from randomization through Week 16Population: The modified intent-to-treat (mITT) population was defined to include all randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Number of Participants With at Least 1 Clinically Relevant and Objectively Confirmed Thrombovascular Event From Randomization Through Week 16
|
5 particpants
|
10 particpants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: The modified intent-to-treat (mITT) population used for safety analysis population included all randomized participants who received at least 1 dose of study drug.
The number of participants who have at least 1 clinically relevant and objectively confirmed (adjudicated) thrombovascular event (TVE) during the study.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Number of Positively Adjudicated Thrombovascular Events
|
5 participants
|
13 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Time to First Positively Adjudicated Thrombovascular Event
|
5 participants
|
13 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Number of Suspected Thrombovascular Events
|
9 participants
|
20 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All randomized participants who received at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Time to First Suspected Thrombovascular Event
|
9 participants
|
20 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All randomized participants who received at least 1 dose of study drug.
Number of participants who died during the study.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Mortality
|
25 participants
|
26 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All participants who were randomized, regardless of whether or not they received study drug.
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.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Number of Hemoglobin Responders
|
179 participants
|
187 participants
|
SECONDARY outcome
Timeframe: during the study (randomization through week 26)Population: All participants who were randomized, regardless of whether or not they received study drug.
The number of participants who received at least 1 red blood cell (RBC) transfusion (packed RBC or whole blood) during the study.
Outcome measures
| Measure |
Epoetin Alfa QW
n=242 Participants
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 Participants
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Red Blood Cell Transfusions
|
38 participants
|
42 participants
|
Adverse Events
Epoetin Alfa QW
Epoetin Alfa TIW
Serious adverse events
| Measure |
Epoetin Alfa QW
n=242 participants at risk
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 participants at risk
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
7.9%
19/242
|
7.6%
20/262
|
|
Blood and lymphatic system disorders
Anaemia
|
1.7%
4/242
|
0.76%
2/262
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.7%
4/242
|
0.00%
0/262
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.2%
3/242
|
0.38%
1/262
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.83%
2/242
|
1.1%
3/262
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.83%
2/242
|
0.38%
1/262
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.41%
1/242
|
1.5%
4/262
|
|
Infections and infestations
Pneumonia
|
0.83%
2/242
|
3.4%
9/262
|
|
Infections and infestations
Abscess jaw
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Bronchitis
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Endocarditis
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Herpes zoster
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Sepsis
|
0.41%
1/242
|
0.76%
2/262
|
|
Infections and infestations
Septic shock
|
0.41%
1/242
|
0.00%
0/262
|
|
Infections and infestations
Abdominal wall abscess
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Erysipeloid
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Gastrointestinal infection
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Kidney infection
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Pneumonia primary atypical
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/242
|
0.38%
1/262
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/242
|
0.38%
1/262
|
|
Vascular disorders
Deep vein thrombosis
|
1.2%
3/242
|
1.5%
4/262
|
|
Vascular disorders
Hypotension
|
0.41%
1/242
|
0.00%
0/262
|
|
Vascular disorders
Hypovolaemic shock
|
0.41%
1/242
|
0.00%
0/262
|
|
Vascular disorders
Thrombosis
|
0.41%
1/242
|
0.00%
0/262
|
|
Vascular disorders
Venous thrombosis
|
0.41%
1/242
|
0.76%
2/262
|
|
Vascular disorders
Venous thrombosis limb
|
0.41%
1/242
|
0.38%
1/262
|
|
Vascular disorders
Cardiovascular insufficiency
|
0.00%
0/242
|
0.38%
1/262
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.00%
0/242
|
0.38%
1/262
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/242
|
0.38%
1/262
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.83%
2/242
|
0.38%
1/262
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.41%
1/242
|
0.00%
0/262
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.41%
1/242
|
0.00%
0/262
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.41%
1/242
|
0.00%
0/262
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.41%
1/242
|
0.00%
0/262
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.41%
1/242
|
0.00%
0/262
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.41%
1/242
|
0.38%
1/262
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/242
|
1.5%
4/262
|
|
Gastrointestinal disorders
Subileus
|
0.83%
2/242
|
0.00%
0/262
|
|
Gastrointestinal disorders
Vomiting
|
0.83%
2/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Ascites
|
0.41%
1/242
|
0.00%
0/262
|
|
Gastrointestinal disorders
Diarrhoea
|
0.41%
1/242
|
0.00%
0/262
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.41%
1/242
|
0.00%
0/262
|
|
Gastrointestinal disorders
Mesenteric artery thrombosis
|
0.41%
1/242
|
0.00%
0/262
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.00%
0/242
|
0.38%
1/262
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/242
|
0.38%
1/262
|
|
General disorders
General physical health deterioration
|
0.83%
2/242
|
0.38%
1/262
|
|
General disorders
Asthenia
|
0.41%
1/242
|
0.00%
0/262
|
|
General disorders
Fatigue
|
0.41%
1/242
|
0.00%
0/262
|
|
General disorders
Multi-organ failure
|
0.41%
1/242
|
0.00%
0/262
|
|
General disorders
Pyrexia
|
0.41%
1/242
|
0.38%
1/262
|
|
General disorders
Chest pain
|
0.00%
0/242
|
0.76%
2/262
|
|
General disorders
Death
|
0.00%
0/242
|
0.38%
1/262
|
|
General disorders
Localised oedema
|
0.00%
0/242
|
0.38%
1/262
|
|
General disorders
Pain
|
0.00%
0/242
|
0.38%
1/262
|
|
General disorders
Sudden cardiac death
|
0.00%
0/242
|
0.38%
1/262
|
|
Metabolism and nutrition disorders
Anorexia
|
0.41%
1/242
|
0.00%
0/262
|
|
Metabolism and nutrition disorders
Cachexia
|
0.41%
1/242
|
0.00%
0/262
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.41%
1/242
|
0.00%
0/262
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.41%
1/242
|
0.00%
0/262
|
|
Cardiac disorders
Cardiogenic shock
|
0.41%
1/242
|
0.00%
0/262
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.41%
1/242
|
0.38%
1/262
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/242
|
0.38%
1/262
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/242
|
0.38%
1/262
|
|
Cardiac disorders
Congestive cardiomyopathy
|
0.00%
0/242
|
0.38%
1/262
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/242
|
0.38%
1/262
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.41%
1/242
|
0.00%
0/262
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.41%
1/242
|
0.00%
0/262
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/242
|
0.38%
1/262
|
|
Immune system disorders
Hypersensitivity
|
0.41%
1/242
|
0.00%
0/262
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.41%
1/242
|
0.00%
0/262
|
|
Injury, poisoning and procedural complications
Pubic rami fracture
|
0.00%
0/242
|
0.38%
1/262
|
|
Injury, poisoning and procedural complications
Stent occlusion
|
0.00%
0/242
|
0.38%
1/262
|
|
Nervous system disorders
Syncope
|
0.41%
1/242
|
0.00%
0/262
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/242
|
0.76%
2/262
|
|
Nervous system disorders
Spinal cord compression
|
0.00%
0/242
|
0.38%
1/262
|
|
Renal and urinary disorders
Renal failure acute
|
0.41%
1/242
|
0.38%
1/262
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/242
|
0.76%
2/262
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/242
|
0.38%
1/262
|
|
Congenital, familial and genetic disorders
Aplasia
|
0.00%
0/242
|
0.38%
1/262
|
|
Hepatobiliary disorders
Acute hepatic failure
|
0.00%
0/242
|
0.38%
1/262
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/242
|
0.38%
1/262
|
Other adverse events
| Measure |
Epoetin Alfa QW
n=242 participants at risk
epoetin alfa at an initial dosage of 450 IU/kg once a week (QW)
|
Epoetin Alfa TIW
n=262 participants at risk
epoetin alfa at an initial dosage of 150 IU/kg 3 times a week (TIW)
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
33.5%
81/242
|
27.5%
72/262
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
21.5%
52/242
|
20.6%
54/262
|
|
Blood and lymphatic system disorders
Leukopenia
|
21.1%
51/242
|
16.8%
44/262
|
|
Gastrointestinal disorders
Nausea
|
11.2%
27/242
|
15.3%
40/262
|
|
Gastrointestinal disorders
Diarrhoea
|
10.7%
26/242
|
3.8%
10/262
|
|
Gastrointestinal disorders
Vomiting
|
5.4%
13/242
|
9.2%
24/262
|
|
General disorders
Asthenia
|
8.7%
21/242
|
5.3%
14/262
|
|
General disorders
Fatigue
|
7.0%
17/242
|
6.1%
16/262
|
|
General disorders
Pyrexia
|
6.2%
15/242
|
6.9%
18/262
|
|
Metabolism and nutrition disorders
Anorexia
|
5.4%
13/242
|
4.2%
11/262
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.4%
13/242
|
2.7%
7/262
|
Additional Information
Clinical Development Team Lead
Johnson and Johnson PRD
Results disclosure agreements
- Principal investigator is a sponsor employee Generally, the only disclosure restriction on the PI is that the sponsor has 60 days to review results communications prior to public release and can embargo communications regarding trial results for a period that does not exceed 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER