Epoetin Alfa in Treating Patients With Anemia Who Are Undergoing Chemotherapy for Cancer

• Sponsor: OHSU Knight Cancer Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00258440
• Collaborator: Ortho Biotech, Inc. (Industry)
• Enrollment: 7
• Location: 1
• Arms: 3
• Duration (Months): 64.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Fatigue; Unspecified Adult Solid Tumor, Protocol Specific	Drug: Weekly procrit dosing; Drug: Interval Dosing	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: A Pilot Trial of Extended Interval Dosing of Epoetin Alfa (Procrit®) for the Treatment of Anemia in Oncology Patients
• Study Start Date: May 1, 2003
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Weekly Procrit (epoetin alfa) dosing Weekly dosing schedule subjects will get the study drug once every week until the end of the study.	Drug: Weekly 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.
Experimental: Interval Dosing (epoetin alfa) PK Group 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. Subjects who consented to pharmacokinetic testing	Drug: Interval Dosing; The dosing of Procrit is standard of care, it is the schedule that is the investigational piece.
Experimental: Interval Dosing (epoetin alfa) Non PK Group 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. Subjects who did not consent to pharmacokinetic testing.	Drug: Interval Dosing; The dosing of Procrit is standard of care, it is the schedule that is the investigational piece.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks [12 weeks]

Secondary Outcome Measures

1. Pharmacokinetics (PK) and Pharmacodynamics Assays That Measure Concentration of Erythropoietin in Serum. [every other week]

2. Quality of Life at Baseline and Weeks 4, 8, 16, 24, and 28 [weeks 4,8,16,24 and 28]

3. Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability. [On study, averaging 3 to 6 months.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OHSU Knight Cancer Institute	Portland	Oregon	United States	97239-3098

Sponsors and Collaborators

• OHSU Knight Cancer Institute
• Ortho Biotech, Inc.

Investigators

• Principal Investigator: Joseph Bubalo, PharmD, BCPS, BCOP, OHSU Knight Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph Bubalo, PharmD, OHSU Knight Cancer Institute
• ClinicalTrials.gov Identifier: NCT00258440
• Other Study ID Numbers: CDR0000445450; OHSU-ONC-03017-LP; OHSU-1616; OHSU-7754; ORTHO-ONC-03017-LP
• First Posted: Nov 24, 2005
• Last Update Posted: May 9, 2017
• Last Verified: May 1, 2017

• Keywords provided by Joseph Bubalo, PharmD, OHSU Knight Cancer Institute: fatigue; anemia; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Anemia; Fatigue; Epoetin Alfa

Study Results

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.

Arm/Group Title	Weekly Procrit (Epoetin Alfa) Dosing	Interval Dosing (Epoetin Alfa) PK Group	Interval Dosing (Epoetin Alfa) Non PK Group
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	1	0	6
COMPLETED	1	0	5
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	Weekly Procrit (Epoetin Alfa) Dosing	Interval Dosing (Epoetin Alfa) PK Group	Interval Dosing (Epoetin Alfa) Non PK Group	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	1	0	6	7
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 0%
Between 18 and 65 years	1 100%	6 Infinity	7 116.7%
>=65 years	0 0%	0 NaN	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	5 Infinity	5 83.3%
Male	1 100%	1 Infinity	2 33.3%
Region of Enrollment (participants) [Number]
United States	1 100%	6 Infinity	7 116.7%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects That Maintained Target Hemoglobin Level (11-12 g/dL) Maintenance Weekly for 12 Weeks
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Due to low accrual numbers and the discontinuation of the study early a full analysis was not completed.

Arm/Group Title	Weekly Procrit (Epoetin Alfa) Dosing	Interval Dosing (Epoetin Alfa) PK Group	Interval Dosing (Epoetin Alfa) Non PK Group
Arm/Group Description	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.	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.	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.
Measure Participants	1	0	6
Number [participants]	0 0%	5 Infinity

2. Secondary Outcome

Title	Pharmacokinetics (PK) and Pharmacodynamics Assays That Measure Concentration of Erythropoietin in Serum.
Time Frame	every other week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Quality of Life at Baseline and Weeks 4, 8, 16, 24, and 28
Time Frame	weeks 4,8,16,24 and 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Number of Adverse Events (AEs) Experienced as Measure of Safety and Tolerability.
Time Frame	On study, averaging 3 to 6 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Weekly Procrit (Epoetin Alfa) Dosing	Interval Dosing (Epoetin Alfa) PK Group	Interval Dosing (Epoetin Alfa) Non PK Group
Arm/Group Description	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.	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.	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.
Measure Participants	1	0	6
Number [events]	38	130

Adverse Events

Time Frame	Adverse Events were collected for as long as the patient was on study. in some cases that was up to 6 months or as little as 3 months.
Arm/Group Title	Weekly Procrit (Epoetin Alfa) Dosing		Interval Dosing (Epoetin Alfa) PK Group		Interval Dosing (Epoetin Alfa) Non PK Group
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Weekly Procrit (Epoetin Alfa) Dosing		Interval Dosing (Epoetin Alfa) PK Group		Interval Dosing (Epoetin Alfa) Non PK Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Weekly Procrit (Epoetin Alfa) Dosing		Interval Dosing (Epoetin Alfa) PK Group		Interval Dosing (Epoetin Alfa) Non PK Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		1/6 (16.7%)
Blood and lymphatic system disorders
Failure to thrive, GI bleed, Malignant Hypercalcemia	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Infections and infestations
Fever Neutropenia	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Weekly Procrit (Epoetin Alfa) Dosing		Interval Dosing (Epoetin Alfa) PK Group		Interval Dosing (Epoetin Alfa) Non PK Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)		6/6 (100%)
Blood and lymphatic system disorders
lymphopenia	1/1 (100%)	6	0/0 (NaN)	0	5/6 (83.3%)	22
Platelets	1/1 (100%)	6	0/0 (NaN)	0	5/6 (83.3%)	21
Leukocytes	1/1 (100%)	3	0/0 (NaN)	0	2/6 (33.3%)	7
Hyperglycemia	1/1 (100%)	4	0/0 (NaN)	0	5/6 (83.3%)	7
Hemorrhage, nose	1/1 (100%)	1	0/0 (NaN)	0	0/6 (0%)	0
Hemorrhage, urine trace	1/1 (100%)	1	0/0 (NaN)	0	0/6 (0%)	0
Bilateral lower extremity edema	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Thigh swelling	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Gastrointestinal disorders
Abdominal bloating	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Abdominal cramping	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Abdominal pain	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Anorexia	0/1 (0%)	0	0/0 (NaN)	0	3/6 (50%)	3
Constipation	0/1 (0%)	0	0/0 (NaN)	0	2/6 (33.3%)	2
Diarrhea	0/1 (0%)	0	0/0 (NaN)	0	2/6 (33.3%)	2
Dysphagia	0/1 (0%)	0	0/0 (NaN)	0	2/6 (33.3%)	3
Esophageal pain	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Heartburn	1/1 (100%)	1	0/0 (NaN)	0	0/6 (0%)	0
Mouth pain	1/1 (100%)	1	0/0 (NaN)	0	0/6 (0%)	0
Mucositis	0/1 (0%)	0	0/0 (NaN)	0	2/6 (33.3%)	2
Increasing abdominal distension	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Pain upper abdomen	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	2
Vomiting	0/1 (0%)	0	0/0 (NaN)	0	2/6 (33.3%)	2
Abdominal pain/tumor pain	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
General disorders
Fatigue	1/1 (100%)	2	0/0 (NaN)	0	5/6 (83.3%)	8
Nausea	1/1 (100%)	1	0/0 (NaN)	0	3/6 (50%)	8
Infections and infestations
Hepatitis	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Upper respiratory infection	0/1 (0%)	0	0/0 (NaN)	0	1/6 (16.7%)	1
Metabolism and nutrition disorders
Abnormal metabolic labs	1/1 (100%)	12	0/0 (NaN)	0	5/6 (83.3%)	31

Limitations/Caveats

Due to low accruals the sponsor decided to discontinue the study early. A full analysis was not completed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.