Peripheral Neuropathy, Chemotherapy-induced
Conditions
Keywords
Peripheral neuropathy, Chemotherapy-induced, Hemoglobin level, Cancer, Taxane, Platinum-based chemotherapy
Brief summary
The purpose of this study is to evaluate the neuroprotective effect of PROCRIT (epoetin alfa, a glycoprotein that stimulates red blood cell production) versus placebo in patients with cancer who develop chemotherapy-induced peripheral neuropathy due to combination Taxane and Platinum-Based treatment.
Detailed description
Peripheral neuropathy is a debilitating disease of the nerves which can be a dose-limiting toxicity of chemotherapeutic agents. The symptoms of peripheral neuropathy can lead to considerable patient distress and discomfort, discontinuation of chemotherapy, and limitations regarding the selection of future chemotherapeutic regimens. Symptoms such as numbness, weakness, burning pain (especially at night), and loss of reflexes may take months before they improve and permanent deficits may remain. Epoetin alfa, already used in the treatment of chemotherapy-induced anemia, has been shown to have neuroprotective effects in preclinical studies. The purpose of this randomized (patients are assigned different treatments based on chance), double-blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), placebo-controlled study is to evaluate the neuroprotective effect of PROCRIT (epoetin alfa) administered once every week in patients with cancer who develop chemotherapy-induced peripheral neuropathy due to treatment with combination Taxane and Platinum-Based chemotherapy. Patients will receive injections subcutaneously or intravenously of either epoetin alfa or placebo once weekly for up to 18 weeks. Doses may be adjusted in the range of 20,000 to 60,000 Units once a week, depending on the patient's hemoglobin levels. Safety evaluations will be conducted throughout the study at specified intervals and will consist of assessment of laboratory tests (Hemoglobin level, Complete Blood Count (CBC), Blood Chemistries), vital signs, physical examinations and occurrence and severity of adverse events. In addition, the occurrence of anti-erythropoietin antibodies at baseline and study completion/early withdrawal will be evaluated in patients who received PROCRIT (Epoetin alfa) after database lock and unblinding has occurred. The primary measure of effectiveness is the change at Week 12 in the National Cancer Institute Common Toxicity Criteria (NCI CTC) neuropathy score. The study hypothesis is that epoetin alfa will be more effective in the treatment of chemotherapy-induced peripheral neuropathy than placebo as measured at Week 12 by the National Cancer Institute Common Toxicity Criteria (NCI CTC) neuropathy score. Patients will receive injections subcutaneously (SC, under the skin) or intravenously (IV, in a vein) of either epoetin alfa or placebo once weekly for up to 18 weeks. Doses may be adjusted depending on the patient's hemoglobin levels to the maximum 60,000 Units once a week. The minimum dose can be 20,000 Units once a week.
Interventions
DRUGPROCRIT 40,000 IU QW
Epoetin alpha (PROCRIT) 40,000 IU every week (QW) for 18 weeks (IV or SC)
DRUGPlacebo
Equivalent volume to PROCRIT (1 mL) administered (QW) for 18 weeks (IV or SC)
Sponsors
Ortho Biotech Clinical Affairs, L.L.C.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a diagnosis of cancer , and no history of peripheral neuropathy * Have had the appropriate surgery for carcinoma and are no more than 12 weeks post-operatively at study entry * Have not received chemotherapy (chemotherapy naïve patients) and are scheduled to receive at least 4 cycles of combination taxane and platinum-based chemotherapy * Have a hemoglobin value of \>= 10 and \< 12 g/dL * have a life expectancy of at least 6 months
Exclusion criteria
* Patients who have had prior treatment with PROCRIT (epoetin alfa) or similar drugs (erythropoietic agents) within the last 2 months * Have used experimental treatments within the last year that are reported or hypothesized to have neuroprotective potential, including amifostine, cyanocobalamin (vitamin B12), alpha-tocopherol (Vitamin E), glutamine, and gabapentin * have anemia due to factors other than cancer/chemotherapy, or have ongoing neuropathy due to any cause * Received a transfusion of platelets or packed red blood cells within 28 days prior to the first dose of study medication * Have a history of pulmonary emboli, deep vein thrombosis, ischemic stroke or any other history of arterial or venous thrombotic events
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 1) at Week 12. | Baseline to Week 12 | NCI CTC neuropathy: a descriptive terminology used to grade the severity of AEs in cancer subjects on a 0-5 scale. A higher score indicates worse peripheral neuropathy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 2) at Week 12. | baseline to Day 128 | NCI CTC neuropathy: a descriptive terminology used to grade the severity of AEs in cancer subjects on a 0-5 scale. A higher score indicates worse peripheral neuropathy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PROCRIT 40,000 IU QW Epoetin alpha (PROCRIT) 40,000 IU every week (QW) for 18 weeks (intravenous or subcutaneous) | 19 |
| Placebo Equivalent volume to PROCRIT (1 mL) administered every week (QW) for 18 weeks (intravenous or subcutaneous) | 11 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | PROCRIT 40,000 IU QW | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 3 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 8 Participants | 19 Participants |
| Age, Continuous | 60.1 years STANDARD_DEVIATION 14.18 | 56.8 years STANDARD_DEVIATION 12.98 | 58.9 years STANDARD_DEVIATION 13.62 |
| Sex: Female, Male Female | 19 Participants | 11 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / — | 11 / — |
| serious Total, serious adverse events | 6 / — | 1 / — |
Outcome results
Primary
The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 1) at Week 12.
NCI CTC neuropathy: a descriptive terminology used to grade the severity of AEs in cancer subjects on a 0-5 scale. A higher score indicates worse peripheral neuropathy.
Time frame: Baseline to Week 12
Population: MITT(Modified intent to treat)all randomized subjects that received at least one dose and had at least one post-baseline neuropathy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PROCRIT 40,000 IU QW | The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 1) at Week 12. | 5 participants |
| Placebo | The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 1) at Week 12. | 6 participants |
Secondary
The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 2) at Week 12.
NCI CTC neuropathy: a descriptive terminology used to grade the severity of AEs in cancer subjects on a 0-5 scale. A higher score indicates worse peripheral neuropathy.
Time frame: baseline to Day 128
Population: MITT(Modified intent to treat)all randomized subjects that received at least one dose and had at least one post-baseline neuropathy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PROCRIT 40,000 IU QW | The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 2) at Week 12. | 3 participants |
| Placebo | The Number of Patients Who Developed Peripheral Sensory Neuropathy (National Cancer Institute Common Toxicity Criteria (NCI CTC) Score >= 2) at Week 12. | 0 participants |