Phase II Trial of Rifaximin in Patients With Early Stage HER2 Positive Breast Cancer With Gastrointestinal Toxicities Related to Pertuzumab-Based Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Reduction Rate of >= Grade 2 Abdominal Toxicities Including Abdominal Distension, Abdominal Pain, Diarrhea, Dyspepsia, Stomach Pain, and Typhlitis
研究概览
简要总结
This phase II trial studies how well rifaximin works for the treatment of gastrointestinal toxicities related to pertuzumab-based therapy in patients with stage I-III HER2 positive breast cancer. Rifaximin may reduce the incidence and severity of pertuzumab induced gastrointestinal toxicities without interrupting or delaying the chemotherapy schedule.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the reduction rate of grade >= 2 abdominal toxicities, including abdominal distension, abdominal pain, diarrhea, dyspepsia, stomach pain, and typhlitis according to the National Cancer Institute Common Terminology for Adverse Events version 5.0 (NCI CTCAE v5.0) with the use of rifaximin in stage II-III HER-2 positive breast cancer patients with pertuzumab induced gastrointestinal toxicities.
SECONDARY OBJECTIVES:
I. Evaluate dose reductions, dose delays and discontinuation of treatment with pertuzumab due to gastrointestinal side effects.
II. Evaluate and measure the change in the Bristol stool scale before and after rifaximin treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •PRE-REGISTRATION INCLUSION CRITERIA
- •Age >= 18 years
- •Histological confirmation of HER2 positive breast cancer stage I-III per American Joint Committee on Cancer (AJCC) staging 8th edition
- •Provide written informed consent
- •Breast cancer patients who will be receiving pertuzumab-based chemotherapy with either TCHP (docetaxel, carboplatin, trastuzumab, and pertuzumab) or docetaxel/paclitaxel, trastuzumab, and pertuzumab
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Hemoglobin >= 10.0 g/dL (obtained =< 30 days prior to pre-registration)
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 30 days prior to pre-registration)
- •Platelet count >= 100 x 10^9/L (obtained =< 30 days prior to pre-registration)
- •Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained =< 30 days prior to pre-registration)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (obtained =< 30 days prior to pre-registration)
- •Serum or plasma creatinine =< 1.5 x ULN (obtained =< 30 days prior to pre-registration)
- •Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 30 days prior to pre-registration)
- •Negative serum pregnancy test done =< 30 days prior to pre-registration, for person of childbearing potential only
- •Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- •Willingness to provide mandatory stool specimen for correlative research
- •Ability to complete questionnaire(s) by themselves or with assistance
- •REGISTRATION INCLUSION CRITERIA
- •Received pertuzumab based regimens in the adjuvant or neoadjuvant setting
- •Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained =< 14 days prior to registration)
- •Platelet count >= 100 x 10^9/L (obtained =< 14 days prior to registration)
- •Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained =< 14 days prior to registration)
- •AST (SGOT)/ALT (SGPT) =< 2.5 x ULN (obtained =< 14 days prior to registration)
- •Serum or plasma creatinine =< 1.5 x ULN (obtained =< 14 days prior to registration)
- •Calculated creatinine clearance >= 45 ml/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)
排除标准
- •PRE-REGISTRATION EXCLUSION CRITERIA
- •History of myocardial infarction =< 6 months prior to pre-registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- •Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
- •EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
- •Uncontrolled intercurrent non-cardiac illness including, but not limited to:
- •Ongoing or active infection
- •Psychiatric illness/social situations
- •Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
- •Any other conditions that would limit compliance with study requirements
- •Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
- •NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
- •Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm (adjust to protocol if applicable)
- •Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- •Pregnant women
- •Nursing women
- •Women of childbearing potential who are unwilling to employ adequate contraception
- •Current colostomy or ileostomy
- •History of inflammatory bowel disease
- •History of irritable bowel syndrome
- •History of arteriovenous malformations
- •History of gastrointestinal bleeds
- •Previous surgical resection of the small bowel or colon
- •Previous allergy to rifaximin or its derivatives
研究组 & 干预措施
Arm I (rifaximin, pertuzumab-based chemotherapy)
Patients that experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy receive rifaximin PO BID on days 1-5 and standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Best Practice (Other)
Arm I (rifaximin, pertuzumab-based chemotherapy)
Patients that experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy receive rifaximin PO BID on days 1-5 and standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
Arm I (rifaximin, pertuzumab-based chemotherapy)
Patients that experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy receive rifaximin PO BID on days 1-5 and standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Rifaximin (Drug)
Arm II (pertuzumab-based chemotherapy)
Patients that do not experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy continue receiving standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Best Practice (Other)
Arm II (pertuzumab-based chemotherapy)
Patients that do not experience PIGT after receiving first standard of care cycle of pertuzumab-based chemotherapy continue receiving standard of care pertuzumab-based chemotherapy on day 1. Treatment repeats every 21 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Reduction Rate of >= Grade 2 Abdominal Toxicities Including Abdominal Distension, Abdominal Pain, Diarrhea, Dyspepsia, Stomach Pain, and Typhlitis
时间窗: Through study completion (approximately 2 years, 3 months)
Based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987).
次要结局
- Dose Reductions of Treatment With Pertuzumab(Up to 3 years)
- Dose Delays of Treatment With Pertuzumab(Up to 3 years)
- Discontinuation of Treatment With Pertuzumab(Up to 3 years)
- Number of Patient With a Reduction of Mean Number of Stools(Up to 3 years)
- Average Maximum Pertuzumab Induced Gastrointestinal Toxicities (PIGT) Score(Baseline (at enrollment); following each treatment cycle (21 days +/- 7 days), up to 5 cycles)