A Phase II Trial to Correlate Early Clinical Response to Pathologic Outcome With Neoadjuvant Systemic Therapy in Patients With Early Stage Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 185
- 试验地点
- 2
- 主要终点
- Change in Clinical Tumor Measurement vs. Pathologic Response
研究概览
简要总结
The purpose of this study is to learn whether clinical response (the amount a tumor shrinks based on imaging or tumor measurements obtained by physical exam) predicts pathologic response (the amount of tumor remaining when surgery is performed) in participants with breast cancer who are receiving chemotherapy prior to surgery.
详细描述
Neoadjuvant therapy was first introduced to improve surgical outcomes of breast cancer and to be able to assess the pathological responsiveness to therapy at the time of surgery. Over time, it became a useful experimental platform in clinical research in breast cancer, and in recent years became an important part of standard management of certain subtypes and clinical stages in breast cancer.
It has been long established that patients who achieve pathologic complete response (pCR, i.e., the absence of any cancer in the tissue removed during surgery) after receiving neoadjuvant treatment have better outcomes than those who don't, especially in HER2+, and triple-negative breast cancer (TNBC). Many reports add aggressive ER+ breast cancer to these groups. So far, the only way to know whether a patient achieved pCR is to give them a full course of therapy and then proceed to surgery.
One of the areas that has attracted significant research interest has been the effort to develop early predictors of pCR. This way, treatment can be tailored in the future to each patient and each tumor and can spare patients ineffective therapy. Some of these predictors include tissue biomarkers, blood based biomarkers, and imaging biomarkers.
It has been observed in neoadjuvant clinical trials that many patients have an impressive early clinical response to treatment after 1-2 cycles of treatment. Anecdotally, many of those patients go on to have a pCR at the time of surgery. This observation, if validated in a prospective clinical trial, may lead to a simple, inexpensive way to assess tumor responsiveness and predict pCR using clinical exam and simple imaging.
Using imaging or molecular changes to predict pCR will also be explored in this study. A consortium of investigators will be studying image analysis and proteogenomic changes early in the course of treatment to predict clinical response specifically in participants with TNBC. Only participants with TNBC will be required to undergo a research biopsy and research MRI prior to starting treatment, and again after the first cycle of 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
- •At least 18 years of age, and legally able to provide informed consent. Both men and women are eligible.
- •Histologically confirmed, invasive breast cancer. Tumor may be triple negative (as defined by ASCO-CAP guidelines), HER2-positive (as defined by ASCO-CAP guidelines), or high-risk estrogen receptor positive (as defined by ASCO-CAP guidelines).
- •To be considered "high risk," at least 2 of the following criteria must be met: 1) histologic grade 3; 2) patient age 50 or less; 3) ER Allred score < 6; 4) Ki-67 ≥ 30%.
- •Tumors must be at least 2 cm by clinical exam or ultrasound
- •Bilateral breast cancers are allowed if the following criteria are met: 1) A lesion on one side (meeting the criteria above) is designated as the index lesion on which study assessments will be performed, and 2) the same treatment regimen is appropriate for both cancers as determined by the treating physician.
- •ECOG performance status of 0 or 1
- •Left ventricular ejection fraction (LVEF) ≥ the institutional lower limit of normal, as assessed by echocardiogram or Multigated Acquisition (MUGA )scan.
- •Adequate organ function, as determined by the following parameters:
- •Absolute Neutrophil Count (ANC) ≥ 1200/mm3
- •Platelets ≥ 100,000/mm3
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ institutional upper limit of normal (ULN), unless patient has Gilbert's disease or similar syndrome
- •Alkaline phosphatase (ALP) ≤ 2.5 x institutional ULN
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
- •Serum creatinine ≤ institutional ULN
- •The participant, if of childbearing potential, is willing to use effective, non-hormonal contraception while on treatment.
- •Participation in a concurrent clinical trial is permitted, with Principal Investigator approval.
排除标准
- •Definitive clinical or radiologic evidence of Stage IV disease
- •Inflammatory breast cancer
- •Participants who are pregnant or lactating
- •History of an excisional biopsy or lumpectomy performed prior to study entry
- •Prior treatment with anthracyclines for any malignancy.
- •Prior treatment for currently diagnosed breast cancer (i.e., endocrine therapy, chemotherapy, targeted therapy, or radiation.
- •History of cardiac disease that would preclude the use of drugs included in these treatment regimens. This includes, but is not limited to:
- •Angina pectoris requiring the use of anti-anginal medication
- •Ventricular arrhythmias except for benign premature ventricular contractions
- •Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
- •Conduction abnormality requiring a pacemaker
- •Valvular disease with documented compromise in cardiac function
- •Symptomatic pericarditis
- •Documented cardiomyopathy
- •History of documented congestive heart failure (CHF)
- •Myocardial infarction documented by elevated cardiac enzymes, or persistent regional wall abnormalities on assessment of left ventricular function.
- •Current HIV, hepatitis B, or hepatitis C infection
- •History of non-breast malignancies (with the exception of in situ cancers treated only by local excision, and basal cell or squamous cell carcinoma of the skin) within 5 years prior to enrollment.
- •Any other non-malignant systemic disease that would preclude treatment with any of the treatment regimens or prevent required follow-up.
- •Any psychiatric or addictive disorders, adverse social situations, or other medical conditions that, in the opinion of the investigator, would preclude the patient from meeting study requirements.
研究组 & 干预措施
Triple Negative Breast Cancer (for tumors > 5 cm)
Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)
干预措施: Paclitaxel (Drug)
Triple Negative Breast Cancer (for tumors > 5 cm)
Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)
干预措施: Carboplatin (Drug)
Triple Negative Breast Cancer (for tumors > 5 cm)
Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)
干预措施: Doxorubicin (Drug)
Triple Negative Breast Cancer (for tumors > 5 cm)
Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)
干预措施: Cyclophosphamide (Drug)
Triple Negative Breast Cancer (for tumors > 5 cm)
Paclitaxel IV plus carboplatin IV (+/- pembrolizumab IV) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (+/- pembrolizumab IV) (4 cycles total)
干预措施: Pembrolizumab (Drug)
Triple Negative Breast Cancer (for tumors < 5 cm)
Paclitaxel IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Paclitaxel (Drug)
Triple Negative Breast Cancer (for tumors < 5 cm)
Paclitaxel IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Doxorubicin (Drug)
Triple Negative Breast Cancer (for tumors < 5 cm)
Paclitaxel IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Cyclophosphamide (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Paclitaxel (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Trastuzumab (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Pertuzumab (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Doxorubicin (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Cyclophosphamide (Drug)
HER2-Positive Breast Cancer
Paclitaxel IV plus Trastuzumab IV plus Pertuzumab IV (or PHESGO) (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV administered (4 cycles total)
干预措施: Pertuzumab/Trastuzumab/Hyaluronidase-zzxf (Drug)
Hormone Receptor Positive Breast Cancer
Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Paclitaxel (Drug)
Hormone Receptor Positive Breast Cancer
Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Doxorubicin (Drug)
Hormone Receptor Positive Breast Cancer
Paclitaxel IV plus Carboplatin IV (4 cycles total), followed by doxorubicin IV plus cyclophosphamide IV (4 cycles total)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Change in Clinical Tumor Measurement vs. Pathologic Response
时间窗: Baseline and at surgery (after 20 weeks)
Clinical tumor measurements are tumor measurements obtain via imaging (mammogram or ultrasound) or by physical exam. Pathologic response is the amount of tumor remaining at the time of surgery, as determined by the pathologist.
次要结局
- Pathologic Complete Response Rate in each Breast Cancer Subtype(20 weeks)
- Predictive value of clinical response following 1 cycle of chemotherapy to predict pathologic complete response(20 weeks)
研究者
Mothaffar Rimawi
Professor
Baylor Breast Care Center