Metformin for Reduction of Paclitaxel Treatment-Related Neuropathy in Patients With Breast Cancer: A Randomized Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Mean Change in Neuropathy
研究概览
简要总结
The goal of this clinical research study is to learn if metformin can help to control nerve damage (loss of motor or sensory function) that may be caused by treatment with paclitaxel in patients with breast cancer.
In this study, metformin will be compared to a placebo. A placebo is not a drug. It looks like the study drug, but it is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in a roll of dice) to 1 of 2 groups. This is done because no one knows if one study group is better, the same, or worse than the other group. You will have a 1 out of 3 chance of being in Group 1 and a 2 out of 3 chance of being in Group 2.
- If you are in Group 1, you will take placebo pills.
- If you are in Group 2, you will take metformin pills.
Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.
Study Drug Administration:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed invasive breast cancer, stage I - IV, treated at Lyndon B. Johnson General Hospital in the Harris Health System.
- •Patients = or > 18 years old and < 75 years old.
- •Patients scheduled to undergo paclitaxel chemotherapy for breast cancer.
- •Patients with adequate renal function, as evidenced in laboratory values = or < 3 months old: epidermal growth factor receptor (eGFR) = or > 60 mL/min/1.73m
- •Patients with adequate hepatic function per institutional testing standards, as evidenced in laboratory values = or < 3 months old: (1) The screening results for total bilirubin must be < 1.5 times the upper limit of normal. (2) The screening results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be < 2 times the upper limit of normal.
- •Patients who speak English and/or Spanish.
- •Patients who are willing and able to review, understand, and provide written consent.
- •Patients with an Eastern Cooperative Oncology performance status of 0 or 1.
排除标准
- •Patients with a history of or known diagnosis of diabetes according to national guidelines (fasting plasma glucose > or = 126 mg/dL or random plasma glucose > or = 200 mg/dL), as evidenced in laboratory values < or = 3 months old).
- •Patients using carbonic anhydrase inhibitors (acetazolamide [Diamox®], brinzolamide [Azopt®], methazolamide [Neptazane®], dorzolamide [Trusopt®], pomegranate ellagitannins), cimetidine, or topiramate.
- •Patients who are enrolled in another symptom management trial.
- •Patients with nerve pathology or clinically identified neuropathy.
- •Patients with a history of clinically significant cutaneous drug reaction, hypersensitivity reaction, anaphylaxis, or any other serious adverse reaction to the medication used in the study.
- •Patients with any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association Class III or IV functional status, history of acidosis of any type).
- •Patients with intestinal issues, including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
- •Patients who are pregnant are excluded. Pre-menopausal women must have a negative pregnancy test. Patients that are post menopausal, or that have had a hysterectomy do not need to have a pregnancy test.
- •Patients with any condition that precludes use of the study medication as determined by the treating physician.
- •Patients with a diagnosis of hepatitis or HIV.
- •Patients currently receiving or scheduled to receive a chemotherapy infusion other than Adriamycin/Cyclophosphamide prior to initiation of the metformin adaptation phase are not eligible. Patients who are receiving Adriamycin/Cyclophosphamide must be scheduled to be at least 8 days post-chemotherapy infusion prior to initiation of the metformin adaptation phase in order to be eligible.
- •Patients who are currently using metformin (eg, Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet).
研究组 & 干预措施
Metformin Group
Participants take 1,000 mg Metformin by mouth twice daily for 12 weeks during Paclitaxel treatment.
Adaptation phase begins 12 days prior to the start of the Paclitaxel therapy. During this phase, study medication dose starts at 500 mg daily for 5 days, followed by 500 mg twice daily for 5 days, followed by the desired dose of 1,000 mg twice daily for 2 days. Participants reach required study medication dose of 2,000 mg daily 2 days prior to commencement of Paclitaxel therapy and continue this dose for remainder of intervention.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Metformin (Drug)
Metformin Group
Participants take 1,000 mg Metformin by mouth twice daily for 12 weeks during Paclitaxel treatment.
Adaptation phase begins 12 days prior to the start of the Paclitaxel therapy. During this phase, study medication dose starts at 500 mg daily for 5 days, followed by 500 mg twice daily for 5 days, followed by the desired dose of 1,000 mg twice daily for 2 days. Participants reach required study medication dose of 2,000 mg daily 2 days prior to commencement of Paclitaxel therapy and continue this dose for remainder of intervention.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Questionnaires (Behavioral)
Metformin Group
Participants take 1,000 mg Metformin by mouth twice daily for 12 weeks during Paclitaxel treatment.
Adaptation phase begins 12 days prior to the start of the Paclitaxel therapy. During this phase, study medication dose starts at 500 mg daily for 5 days, followed by 500 mg twice daily for 5 days, followed by the desired dose of 1,000 mg twice daily for 2 days. Participants reach required study medication dose of 2,000 mg daily 2 days prior to commencement of Paclitaxel therapy and continue this dose for remainder of intervention.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Sensory and Fine-Motor Tests (Other)
Placebo Group
Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Placebo (Other)
Placebo Group
Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Questionnaires (Behavioral)
Placebo Group
Participants take placebo by mouth twice daily starting 12 days before, and 12 weeks during Paclitaxel treatment.
Questionnaires completed about numbness and/or symptoms about 2 weeks before start of Paclitaxel, 1 -2 days before Paclitaxel, every week while taking Paclitaxel, and at end of study visit. At week 12, questionnaire completed regarding satisfaction with Paclitaxel.
Three sensory and fine-motor tests completed 2 weeks before Paclitaxel, every 3 weeks while taking Paclitaxel, and at end of study visit.
干预措施: Sensory and Fine-Motor Tests (Other)
结局指标
主要结局
Mean Change in Neuropathy
时间窗: Up to 14 weeks, assessed every 3 weeks ±1 week (T2, T3, T4, T5) during paclitaxel therapy
Change in neuropathy as assessed with the chemotherapy-induced peripheral neuropathy (CIPN) survey QLQ-CIPN20 between T1 and T5 where difference in mean area under the curve (AUC) between groups reported. The AUC for response from T1 to T5 is computed by fitting a series of trapezoids to the QLQ-CIPN20 data assessed at T1, T2, T3, T4, and T5, respectively, and summing up their areas \[AUC calculated - base of a trapezoid corresponds to the number of days between assessments, and the heights correspond to two adjoining symptom responses, number of trapezoids depends on number of symptom assessments and sum of area for all trapezoids represents AUC of particular participant\]. QLQ-CIPN20 contains 20 items assessing sensory (9 items), motor (8 items), and autonomic symptoms (3 items) using a 4-point Likert scale (1 = "not at all," 2 = "a little," 3 = "quite a bit," and 4 = "very much") with the higher score denoting more symptom burden.
次要结局
未报告次要终点