A Phase II, Placebo-controlled, Double-blind, Randomized Crossover Trial of Pregabalin for the Prophylaxis of Pegfilgrastim-induced Bone Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Number of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1
研究概览
简要总结
Purpose:
To evaluate the preventative effects of pregabalin on pegfilgrastim-induced bone pain in cycle 1. Because granulocyte colony stimulating factor (G-CSF) receptors are found at nerve endings which modulate the pain signal, blocking this with pregabalin is theorized to prevent the occurrence of this adverse effect.
Participants:
Patients will be at least 18 years of age with either a diagnosis of a non-myeloid hematologic malignancy scheduled to initiate a cycle of chemotherapy that requires prophylactic use of a G-CSF, or with a diagnosis of breast cancer scheduled to initiate dose-dense doxorubicin/cyclophosphamide chemotherapy or docetaxel/cyclophosphamide that requires prophylactic use of a G-CSF.
Procedures (methods):
This is a randomized (1:1), single center, placebo-controlled, double blind, crossover phase II study. The primary objective is to compare the proportion of patients who have an increase in pain score of ≥3 from baseline in cycle 1 between Arm A (pregabalin) and Arm B (placebo). In consultation with the treating physician, the PI will determine what day pegfilgrastim will be initiated in each eligible, consented patient. Pregabalin or placebo will begin 4 days prior to pegfilgrastim administration, and continue for 7 additional days starting the day of pegfilgrastim administration.
详细描述
**Study Synopsis**
This is a randomized, double-blind, placebo-controlled, single center, crossover phase II clinical trial investigating the prophylactic analgesic effects of pregabalin (Lyrica®) during the first two cycles of chemotherapy in cancer patients receiving pegfilgrastim (Neulasta®). The investigators have restricted enrollment in this trial to breast cancer patients and those with hematological malignancies, who require pegfilgrastim prophylactically. Pegfilgrastim is associated with bone pain (which can be severe) when used in these populations.
In this study 60 patients are randomized to Arm A (pregabalin in cycle 1; placebo in cycle 2) or Arm B (placebo in cycle 1; pregabalin in cycle 2). The primary objective is to compare the proportion of patients who have an increase in pain score of ≥3 from baseline through the end of study medication in cycle 1 between Arm A (pregabalin) and Arm B (placebo).
A secondary objective is to compare of the proportion of patients with an increase in pain score of ≥3 from baseline between pregabalin and placebo across the 2 cycles. Other outcomes evaluated are the safety of this combination, the proportion of patients with an increase in bone/joint pain score of ≥3 from baseline, the proportion of patients with severe pain, the maximum change in pain score, and time to and number of days of rescue (breakthrough) analgesics.
For measuring pain, the investigators will rely on a validated 10-point numerical pain scale that patients will complete prior to initiation of pregabalin in each cycle, and for 7 days starting the day of pegfilgrastim administration in each cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of a non-myeloid hematologic malignancy scheduled to initiate a cycle of chemotherapy that requires prophylactic use of a granulocyte colony-stimulating growth factor (based on the provider's discretion), provided the schedule of chemotherapy cycles allows the use of pegfilgrastim at a dose of 6 mg SC once per cycle OR Diagnosis of breast cancer scheduled to initiate dose-dense doxorubicin and cyclophosphamide (AC) chemotherapy or docetaxel and cyclophosphamide (TC) chemotherapy that requires prophylactic use of a granulocyte colony-stimulating growth factor, provided the schedule of chemotherapy cycles allows the use of pegfilgrastim, at a dose of 6 mg SC once per cycle; pegfilgrastim scheduled for 24 hours post chemotherapy.
- •Schedule of chemotherapy and pegfilgrastim initiation can accommodate initiation of pregabalin 4 days prior to pegfilgrastim dose.
- •Baseline pain scores <7 as measured via 10-point numerical scale for pain (see section 11.1); pain score and use of any non-opioid pain medication must be self-reported as stable (same dose and frequency) over the 7 days prior to screening; for opioids, patient must self-report the same dose and frequency over the 28 days prior to screening. Patients who are receiving peri-procedural short-acting analgesics will still be included as long as they are no longer receiving analgesics by D1 of chemotherapy.
排除标准
- •A history of (within one month) or current pregabalin use.
- •Baseline pain scores ≥7 as measured via 10-point numerical scale for pain (see section 11.1).
- •Unwilling to discontinue use of antihistamines from 7 days prior to D1 of study medication.
- •Creatinine clearance (CrCl) ≤60 ml/min (as measured via Cockcroft-Gault) based on serum creatinine measured as part of standard of care prior to administration of chemotherapy
- •Women of childbearing potential must have a negative serum pregnancy test prior to initiating therapy (note, this test should be standard of care prior to administration of chemotherapy).
- •Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.
- •Eligible and agrees to enroll into therapeutic trial ongoing at the Lineberger Comprehensive Cancer Center (LCCC) (i.e., the treatment trial will take precedence over LCCC1314).
- •Currently receiving therapeutic doses of anticoagulants (ie, prophylactic use of anticoagulants is allowed) due to possibility of dizziness and falls while on pregabalin.
- •Currently receiving aromatase inhibitors or agents targeted against Ph+ leukemias (i.e., imatinib, dasatinib, nilotinib, and ponatinib) or scheduled to start these drugs during cycle 1 of scheduled chemotherapy.
- •Presence of bone metastases.
- •History of angioedema.
- •History of a seizure disorder.
研究组 & 干预措施
Pregabalin, then Placebo
Pregabalin in cycle 1; placebo in cycle 2.
Pregabalin or matching placebo will be administered at 75 mg twice a day (BID) for 4 days, to patients receiving pegfilgrastim for hematologic malignancies or breast cancer patients on myelosuppressive chemotherapy . Starting the day of pegfilgrastim, the dose of study medication will be increased to 150 mg PO BID provided the patient is tolerating the lower dose (ie, they are not experiencing any pregabalin associated toxicities >Grade 1). This will be determined by the research team on the day of pegfilgrastim administration.
干预措施: Pregabalin (Drug)
Placebo, then Pregabalin
Placebo in cycle 1; pregabalin in cycle 2.
Pregabalin or matching placebo will be administered at 75 mg BID for 4 days, to patients receiving pegfilgrastim for hematologic malignancies or breast cancer patients on myelosuppressive chemotherapy . Starting the day of pegfilgrastim, the dose of study medication will be increased to 150 mg PO BID provided the patient is tolerating the lower dose (ie, they are not experiencing any pregabalin associated toxicities >Grade 1). This will be determined by the research team on the day of pegfilgrastim administration.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1
时间窗: Up to 12 weeks
Compare the proportion of patients who have an increase in pain score of ≥ 3 from baseline through the end of study medication in cycle 1 between Arm A and Arm B. The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine."
次要结局
- Maximum Change in Pain Score From Baseline Between Pregabalin and Placebo Across the 2 Cycles(Up to 12 weeks)
- Proportion of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Between Pregabalin and Placebo Across the 2 Cycles(Up to 12 weeks)
- Maximum Neuropathic Pain Score Between Pregabalin and Placebo Across the 2 Cycles(Up to 12 weeks)
- Proportion of Patients Who Have an Increase in Bone/Joint Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1(Up to 12 weeks)
- Number of Days of Breakthrough Analgesic Use Between Pregabalin and Placebo Across the 2 Cycles(Up to 12 weeks)
- Proportion of Patients With Severe Pain Between Pregabalin and Placebo Across the 2 Cycles(Up to 12 weeks)
- Number of Subjects That Experienced a Grade 2 or Higher Adverse Events When Taking Pregabalin(Up to 12 weeks)