Anemia, Fatigue, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
fatigue, anemia, unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Epoetin alfa may cause the body to make more red blood cells. It is used to treat anemia caused by cancer and chemotherapy. It may also help relieve fatigue in patients with anemia. PURPOSE: This randomized clinical trial is studying how well epoetin alfa works in treating patients with anemia who are undergoing chemotherapy for cancer.
Detailed description
OBJECTIVES: Primary * Determine the efficacy, in terms of maintenance of target hemoglobin and hematocrit levels, of interval dosing with epoetin alfa in treating patients with anemia undergoing chemotherapy for nonhematologic cancer. Secondary * Determine the pharmacokinetics and pharmacodynamics of this drug in these patients. * Correlate hemoglobin and hematocrit response with patient age (\> 65 years vs \< 65 years) in patients treated with this drug. * Determine quality of life of patients treated with this drug. * Determine the adverse effects of this drug in these patients. * Determine the change over time of symptom and quality of life variables (e.g., fatigue) in patients treated with this drug. OUTLINE: This is a partially randomized, pilot study. Patients are stratified according to age (\< 65 years vs ≥ 65 years). Patients are assigned to 1 of 2 treatment groups based on participation in the pharmacokinetic (PK) portion of the study. * Group 1 (PK study, initial therapy): Patients are randomized to 1 of 2 treatment arms. * Arm I: Five patients receive epoetin alfa subcutaneously (SC) once weekly. Treatment continues for 24 weeks in the absence of unacceptable toxicity. * Arm II: Five patients receive epoetin alfa SC once weekly until hematocrit is \> 36% OR hemoglobin reaches a value of 12 g/dL. Patients then proceed to maintenance therapy. Patients in both arms also undergo PK sampling periodically during study treatment. * Group 2 (non-PK study, initial therapy): Fifteen patients receive epoetin alfa SC once weekly until hematocrit is \> 36% OR hemoglobin reaches a value of 12 g/dL. Patients then proceed to maintenance therapy. * Maintenance therapy: Patients receive epoetin alfa SC once every other week for up to 24 weeks of total treatment (including both initial therapy and maintenance therapy). Patients whose blood counts fall below the critical levels are placed on a weekly dosing schedule. Patients whose blood counts rise too high discontinue study drug until blood counts are reduced. Quality of life (including fatigue) is assessed at baseline and then every 4 weeks for 28 weeks. After completion of study therapy, patients are followed at 4 weeks. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Interventions
DRUGWeekly procrit dosing
The dose is standard of care, the investigational piece is the dosing schedule itself. Either weekly or Interval-dosing schedule subjects will get the study drug once every week until hematocrit is greater than 36% or Hemoglobin reaches a value of 12 g/dl, then they will get study drug once every other week.
DRUGInterval Dosing
The dosing of Procrit is standard of care, it is the schedule that is the investigational piece.
Sponsors
Ortho Biotech, Inc.
OHSU Knight Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
ELIGIBILITY CRITERIA * 18 years of age or greater * Must have Hb less than 11 g/dl and normal hematopoesis * Must have non-myeloid malignancies treated with myelosuppressive therapy \*Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Must have a life expectancy of 6 months or greater * Must have adequate liver function (bilirubin less than or equal to 2.0 mg) and renal function (creatinine less than or equal to 2.0 mg) * Must have normal serum folate and vitamin B12 levels or be receiving replacement therapy * Must be iron replete (transferring saturation great than or equal to 20 percent and ferritin greater than or equal to 100 mg/ml) or be receiving replacement therapy * Must be able to fully comprehend and give written consent. * Female patients with reproductive potential must be practicing an effective method of birth control (e.g., abstinence, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, surgical sterilization) before entry and throughout the study. * Female patients with reproductive potential must have a negative serum human chorionic gonadotropin (HCG) pregnancy test at screening (within 7 days before the first dose of study drug)
Exclusion criteria
* Patient has uncontrolled hypertension * Patient has history of symptomatic cardiac disease * Patient has serious intercurrent illness * The patient is pregnant, has a positive serum HCG or is lactating Patient has known hypersensitivity to mammalian cell-derived products or human albumin. * Patient has diagnosis of polycythemia vera, chronic myelogenous leukemia, myelodysplastic syndrome * May not be due for transplant within 24 weeks * Anemia due to factors other than cancer. * History of a thrombotic vascular event. * History of seizures * Patient has received a red blood cell growth factor (epoetin alfa or darbepoetin) within the last 60 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) and Pharmacodynamics Assays That Measure Concentration of Erythropoietin in Serum. | every other week |
| Quality of Life at Baseline and Weeks 4, 8, 16, 24, and 28 | weeks 4,8,16,24 and 28 |
| Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability. | On study, averaging 3 to 6 months. |
Countries
United States
Participant flow
Recruitment details
Subjects were adults age \>=18yrs, with solid tumors, and who received treatment. A total of 25 subjects were recruited. Potential study subjects were seen in a routine clinical setting or referred for study purposes. The PI, physician or the research nurse approached subject and to get informed consent, as well as screen for eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Weekly Procrit (Epoetin Alfa) Dosing Patients receive epoetin alfa subcutaneously (SC) once weekly. Treatment continues for 24 weeks in the absence of unacceptable toxicity. Patients then proceed to maintenance therapy. | 1 |
| Interval Dosing (Epoetin Alfa) PK Group Patients receive epoetin alfa SC once weekly until hematocrit is \> 36% OR hemoglobin reaches a value of 12 g/dL. Patients then proceed to maintenance therapy. Patients who have consented to pharmacokinetics (PK) testing. | 0 |
| Interval Dosing (Epoetin Alfa) Non PK Group Patients receive epoetin alfa SC once weekly until hematocrit is \> 36% OR hemoglobin reaches a value of 12 g/dL. Patients then proceed to maintenance therapy. Patients who have NOT consented to pharmacokinetics (PK) testing. | 6 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Weekly Procrit (Epoetin Alfa) Dosing | Interval Dosing (Epoetin Alfa) Non PK Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 6 Participants | 7 Participants |
| Region of Enrollment United States | 1 participants | 6 participants | 7 participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 0 / 0 | 6 / 6 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 | 1 / 6 |
Outcome results
Primary
Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks
Time frame: 12 weeks
Population: Due to low accrual numbers and the discontinuation of the study early a full analysis was not completed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Weekly Procrit (Epoetin Alfa) Dosing | Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks | 0 participants |
| Interval Dosing (Epoetin Alfa) Non PK Group | Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks | 5 participants |
Secondary
Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability.
Time frame: On study, averaging 3 to 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Weekly Procrit (Epoetin Alfa) Dosing | Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability. | 38 events |
| Interval Dosing (Epoetin Alfa) Non PK Group | Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability. | 130 events |
Secondary
Pharmacokinetics (PK) and Pharmacodynamics Assays That Measure Concentration of Erythropoietin in Serum.
Time frame: every other week
Secondary
Quality of Life at Baseline and Weeks 4, 8, 16, 24, and 28
Time frame: weeks 4,8,16,24 and 28