Safely Stopping Pre-Medications in Patients Receiving Paclitaxel: A Randomized Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Proportion of Patients With Grade 2 or Greater Reactions That Require Parenteral Rescue Medications to Treat an Infusion Hypersensitivity Reaction (HSR) After the First 2 Doses of Paclitaxel With or Without Continued Premedication Dosing
研究概览
简要总结
This phase II/III trial investigates the difference in rates of infusion hypersensitivity reaction in patients with breast cancer who are receiving paclitaxel alone or in combination with other cancer drugs which require parenteral rescue medication after stopping standard pre-medications (dexamethasone, diphenhydramine, famotidine/cimetidine/ranitidine), compared to continuing premedications. Paclitaxel is a drug used to treat breast cancer, ovarian cancer, and autoimmune deficiency syndrome (AIDS)-related Kaposi sarcoma. It blocks cell growth by stopping cell division and may kill cancer cells. It is a type of antimitotic agent. However, there are side-effects and toxicities associated with repeat exposure to this pre-medication regimen. With prolonged use of paclitaxel, especially during weekly regimens, patients are exposed to repeat doses of drugs that prevent hypersensitivity reactions. Side effects include, but are not limited to, insomnia, gastritis, fluid retention, weight gain, mood changes and immune suppression. The information gained from this study may positively influence clinical practice and help researchers develop methods to safely stop pre-medications.
详细描述
PRIMARY OBJECTIVE:
I. To estimate the difference in rates of infusion hypersensitivity reaction (HSR) requiring parenteral rescue medications following the discontinuation of pre-medications after 2 doses of paclitaxel, compared to continuing premedications, in breast cancer patients who have not experienced an infusion HSR with their first 2 paclitaxel doses.
OUTLINE:
Patients receive paclitaxel per standard of care as a single agent or in combination with dexamethasone intravenously (IV) and/or orally (PO), diphenhydramine IV and/or PO and either famotidine IV and/or PO, ranitidine IV and/or PO or cimetidine IV and/or PO. Patients who don't experience any infusion hypersensitivity reaction after the first 2 doses of paclitaxel are randomized to 1 of 2 arms.
ARM I (STANDARD OF CARE): Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients scheduled to receive at least 4 doses of paclitaxel as a single-agent or in combination with trastuzumab, pertuzumab, bevacizumab, pembrolizumab, lapatinib, gemcitabine or other drug combination (excluding cisplatin or carboplatin) for the treatment of any stage, histologically confirmed breast cancer
- •Ability to complete questionnaires by themselves or with assistance
- •Life expectancy > 6 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Age >= 18
- •Able to give informed consent
- •Patients must be scheduled to receive prophylactic HSR premedications (IV or oral) consisting of a histamine-1 (H1) antagonist (diphenhydramine) or cetirizine (a histamine-1 (H1) antagonists), dexamethasone (a steroid) and a either famotidine, ranitidine or cimetidine (histamine-2 (H2) antagonists), per institutional guidelines, prior to each of their first 2 doses of paclitaxel
- •Patients may enroll, or currently be enrolled in another concurrent clinical trial provided the other trial would not prohibit the discontinuation of paclitaxel premedications
排除标准
- •Patients who have received at least 1 prior lifetime dose of paclitaxel or paclitaxel albumin-bound
- •Patients receiving paclitaxel in combination with carboplatin or cisplatin (due to risk of hypersensitivity with platinum compounds)
- •History of grade 3 hypersensitivity reaction to Cremophor EL containing medications (e.g. paclitaxel, cyclosporine, ixabepilone, teniposide)
- •Patients receiving therapeutic daily doses of systemic corticosteroids. Intermittent oral steroids for nausea or for acute inflammatory conditions (i.e. methylprednisolone dosepak) and inhaled, intranasal or topical corticosteroids are permitted
- •Patients who are pregnant or nursing. Paclitaxel is classified by the Food and Drug Administration (FDA) as "pregnancy category D". Pregnancy testing (urine or blood human chorionic gonadotropin [Hcg]) will be done and documented prior to enrollment if pregnancy is clinically suspected
研究组 & 干预措施
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Cimetidine (Drug)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Dexamethasone (Drug)
Arm II (paclitaxel)
Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
干预措施: Quality-of-Life Assessment (Other)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Diphenhydramine (Drug)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Famotidine (Drug)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Paclitaxel (Drug)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Quality-of-Life Assessment (Other)
Arm I (paclitaxel, pre-medications)
Patients continue on pre-medications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel.
干预措施: Ranitidine (Drug)
Arm II (paclitaxel)
Patients discontinue premedications (dexamethasone, diphenhydramine, famotidine/ranitidine/cimetidine) with all future doses of paclitaxel, unless patient develops a subsequent infusion HSR.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Proportion of Patients With Grade 2 or Greater Reactions That Require Parenteral Rescue Medications to Treat an Infusion Hypersensitivity Reaction (HSR) After the First 2 Doses of Paclitaxel With or Without Continued Premedication Dosing
时间窗: Up to 2 years and 8 months
The proportion of patients having infusion HSR of grade 2 or greater requiring parental treatment (rescue medications) will be estimated along with a 95% confidence interval. The difference in proportions of patients with grade 2 or greater infusion HSR needing rescue medication will be estimated along with a 95% confidence interval using the Z-test of normal approximations of the binomial distributions. As a sensitivity analysis, will repeat the analysis including patients assigned to the discontinuation arm but decided to restart pre-medications and patients assigned to the continuation arm but demanded to have premedications discontinued as having experienced HSR.
次要结局
- Correlation Between Abbreviated Premedication Regimen Results to Quality of Life (QoL)(Up to 2 years and 8 months)
研究者
Michael Berger, PharmD
Principal Investigator
Ohio State University Comprehensive Cancer Center