A Randomized Phase II Trial Evaluating the Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer
研究概览
简要总结
This multi-center randomized Phase II study assigned HER2-negative early-stage breast cancer patients to receive preoperative systemic chemotherapy in either a "genomic-guided" arm or a "non-guided arm." The "genomic-guided" method (Arm 1) used genomic expression profiling to assign the preoperative therapy (Doxorubicin/Cyclophosphamide (AC) versus Docetaxel/Cyclophosphamide (TC), while Arm 2 used random assignment to these two therapies.
详细描述
Primary Objective 1 was to test for an arm difference in pathological complete response rates. Secondary Objective 2 was to estimate and test the difference in pathologic complete response rates between drug-sensitive patients who received their preferred drug and drug-resistant patients randomized to AC or TC.
Secondary objectives included: to determine the 60% cutoff for the genomic profiles resulted in a larger pathologic CR rate for the guided arm than for the unguided arm; to compare the pathologic CR rates of patients whose genomic predictive probabilities indicated that they were resistant to both chemotherapy regimens with the pathologic CR rates of patients whose genomic predictive probabilities indicated that they were sensitive to only one treatment and who were then randomly assigned to a treatment for which they were resistant (combining AC and TC subgroups); Secondary Objective 3 in patients with T2 and T3 tumors classified as requiring mastectomy at baseline, compare the guided and non-guided treatment arms on rates of breast conserving surgery with negative final margins; Secondary Objective in patients with T2 tumors classified as potential candidates for breast conservation, compare the guided and non-guided arms on rates of breast conserving surgery at first attempt; Secondary Objectives 5, 6, 7 and 8 to correlate genomic profiles (i.e., genomic predictive probabilities) with clinical response, disease-free survival, sites of recurrence, and overall survival; Secondary Objective 9:to compare the mean cost of guided versus non-guided treatment; and Secondary Objective 10 to assess patient perceptions of participating in a clinical trial that evaluated cancer genomics for preoperative systemic therapy of early-stage breast cancer.
Objective 10 details: Due to space limitations in the Outcome Measure Description field, details are supplied here:
To assess patient motivation and participation for study participation in a clinical trial evaluating cancer genomics for treatment patients provided responses for the following questions at both baseline (the day of chemotherapy start) and following post-surgical medical oncology evaluation:
One of the goals of this study is to tailor your cancer treatments for you based upon a genomic analysis of your tumor. How much did the knowledge that the treatment is potentially tailored specifically for your tumor influence your decision to participate in this study? (Select One)
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologic Documentation: Patients must have a histologic (i.e., not just cytologic) diagnosis of invasive breast cancer by core biopsy. Excisional biopsy or incisional biopsy is not allowed. All breast cancer histologic types are allowed.
- •Stage: Any patient with a clinical T1c (>1.5 cm) to T3 invasive breast cancer by the revised TNM staging system (AJCC 6th edition) will be eligible. Any N stage disease is allowed. No distant metastases allowed.
- •Tumor Site: Patients must have invasive cancer in the breast. Multifocal disease (i.e. confined to a single quadrant in the same breast) is allowed. Multicentric disease (i.e. disease in multiple breast quadrants) is not allowed. Determination of multifocal and multicentric disease status will be made by the evaluating surgeon; ambiguous cases will be reviewed by the principal investigator. Patients with synchronous contralateral invasive breast cancers are not eligible; prior contralateral breast cancer allowed as long as patient has not received prior chemotherapy or radiation therapy in the past 5 years.
- •Measurable Disease: Patients must have measurable disease in the breast by imaging studies (mammogram, ultrasound, or MRI), and must be greater than 1.5 cm in at least one dimension by one or more of the imaging assessments.
- •Conventional Biomarker Status: Standard clinical biomarkers for ER, PR, and HER2 must be obtained on the initial diagnostic core biopsy. The invasive cancer must be HER2 negative (i.e. immunohistochemistry score 1-2+ and/or FISH non-amplified). Any ER/PR status is allowed. Patients who are HER2 2+ on initial immunohistochemistry assessment will be further assessed by FISH. In this instance, patient will be consented and further screened for eligibility and have tissue acquired for genomic profiling. If the standard of care additional FISH testing is positive for HER2 gene amplification, the patient will not be randomized and will be treated in the same manner as screen failures.
- •Must be deemed a surgical candidate.
- •Fresh tissue biopsy material must be available for genomics analysis.
- •No prior chemotherapy, radiotherapy, or biologic/targeted therapy for the currently diagnosed breast cancer, or any other malignancy in the past 5 years, is allowed. No prior anthracycline or taxane therapy.
- •Prior malignancies are allowed if the patient is considered to be disease-free for 5 or more years and is deemed to be at low risk for recurrence. Patients with any prior diagnosis of in situ malignancies (melanoma, bladder, colon, cervical, basal cell, or squamous carcinoma) are eligible regardless of time from diagnosis.
- •Aged at least 18 years.
- •ECOG Performance Status 0-
- •Adequate Organ Function:
- •Total bilirubin ≤1.0 x the institutional ULN
- •Hepatic enzymes (AST (SGOT), ALT (SGPT)) ≤1.5x the institutional ULN
- •Alkaline Phosphatase ≤2.5 x ULN
- •Serum creatinine ≤2.0 mg/dl
- •Neutrophil count (ANC or AGC) ≥1000/ μL
- •Platelets ≥100,000/ μL
- •Cardiac Ejection Fraction ≥50% by MUGA, Echo or MRI.
- •Significant cardiac disease that would preclude the use of anthracyclines: No myocardial infarction in the last 6 months; history of congestive heart failure, serious cardiac arrhythmia requiring medication, active coronary artery disease/angina pectoris requiring therapy, uncontrolled hypertension defined as BP >150/90 despite medication; any other unstable cardiac condition as perceived by treating physician or study PI.
- •No other serious medical or psychiatric illness.
- •Pregnancy: Patients may not be pregnant or nursing at the time of enrollment and other restrictions apply.
- •Signed written informed consent including HIPAA.
排除标准
- •Patients who have received investigational drugs within 4 weeks prior to starting study drug and/or who have not recovered from side effects of such therapy are not eligible.
研究组 & 干预措施
Guided Arm
Genomically-guided treatment allocation.
This arm has the following cohorts:
- AC sensitive patients [>60% probability of response to AC]
- TC sensitive patients [>60% probability of response to TC]
- Patients sensitive to neither AC nor TC; randomized to AC or TC
干预措施: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC) (Drug)
Non-Guided Arm
Non-genomically-guided treatment allocation.
This arm has the following cohorts:
-
In patients randomly assigned to AC:
-
Patients sensitive to AC
-
Patients sensitive to TC
-
Patients sensitive to neither AC nor TC
-
In patients randomly assigned to TC:
-
Patients sensitive to AC
-
Patients sensitive to TC
-
Patients sensitive to neither AC nor TC
干预措施: Doxorubicin/Cyclophosphamide (AC) or Docetaxel/Cyclophosphamide (TC) (Drug)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer
时间窗: 4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks
Pathological complete response (pCR) was defined as the disappearance of all invasive disease in the breast or if only residual in situ or lymph node disease is found. The pCR rate is presented with its 95% confidence interval for the Guided and Non-guided arms.
次要结局
- Percentage of Patients Who Had Breast-conserving Surgery With Negative Margins(6 months)
- To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.(6 months)
- Sites of Recurrence(10 years)
- Overall Survival(2 years)
- Economic Impact of Using Genomic Assessment to Guide Management.(5 years)
- Patients' Perceptions of Participating in a Clinical Trial Evaluating Cancer Genomics for PST of Early-stage Breast Cancer.(1 year)
- Probabilities of Being Sensitive to AC and TC as Determined by the Patient's Genomic Signatures(10 years)
- Clinical Response Using WHO Criteria(12 weeks, 2-3 weeks after the fourth cycle of chemotherapy)
- Disease-free Survival(2 years)