The Impact of HER2 Heterogeneity on the Treatment of Early-stage HER2-positive Breast Cancer: a Phase II Study of T-DM1 in Combination With Pertuzumab in the Preoperative Setting
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 164
- 试验地点
- 5
- 主要终点
- Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous
研究概览
简要总结
This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2.
The names of the study interventions involved in this study are:
- Trastuzumab emtansine (also called T-DM1)
- Pertuzumab
详细描述
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for pre-operative use in breast cancer but it has been approved for other uses in breast cancer. The FDA has approved pertuzumab as a pre-operative treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients must have HER2-positive Stage II or III histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or imaging is required.
- •HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH positive based on one of the three following criteria:
- •Single-probe average HER2 copy number≥6.0 signals/cell OR
- •Dual-probe HER2/CEP17 <2.0 with an average HER2 copy number ≥6.0 signals/cell OR
- •Dual-probe HER2/CEP17 ratio ≥2.0
- •ER/PR determination is required.
- •Bilateral breast cancers are allowed if both cancers are HER2-positive.
- •Patients with multifocal or multicentric disease are eligible as long as one area meets eligibility criteria.
- •Breast imaging should include the ipsilateral axilla. For subjects with a clinically negative axilla, a sentinel lymph node biopsy will be performed either before or after preoperative therapy at the discretion of the subject's physicians. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to determine the presence of metastatic disease in the lymph nodes.
- •Men and women (with any menopausal status) ≥ 18 years of age
- •ECOG performance status 0 or 1
- •Required laboratory values:
- •ANC ≥1500/mm3
- •Hemoglobin ≥ 9 g/dl
- •Platelets ≥100,000/mm3
- •Serum creatinine < 1.5 X ULN (institutional)
- •Total bilirubin ≤ 1.0 X ULN (institutional) For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range.
- •AST and ALT ≤ 1.5x ULN (institutional)
- •Alkaline phosphatase ≤1.5x ULN (institutional)
- •Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B core antibody (HBcAb) in addition to HCV antibody testing.
- •Only for patients who test positive for hep B/C virus: PTT/INR < ULN (institutional)
- •Left ventricular ejection fraction (LVEF) ≥ 55%
- •Premenopausal women must have a negative serum pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause.
- •Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment.
- •Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with T-DM
- •Excessive alcohol intake should be avoided (occasional use is permitted).
- •Patients with a history of ipsilateral DCIS are eligible.
- •Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy.
- •Willing and able to sign informed consent.
- •Willing to provide tissue for research purposes.
排除标准
- •Pregnant or nursing women due to the teratogenic potential of the study drugs.
- •Active, unresolved infection.
- •Receipt of intravenous antibiotics for infection within 7 days prior to enrollment.
- •Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis.
- •Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication.
- •Significant symptoms (Grade ≥2) peripheral neuropathy.
- •Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.
- •Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.
研究组 & 干预措施
T-DM1 and Pertuzumab
T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.
干预措施: T-DM1 (Drug)
T-DM1 and Pertuzumab
T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.
干预措施: Pertuzumab (Drug)
T-DM1 and Pertuzumab
T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.
干预措施: Excision of tumor/mastectomy (Procedure)
结局指标
主要结局
Rate of Pathologic Complete Response (pCR) by HER2 Amplification Status Non-Heterogeneous
时间窗: Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.
The rate of pCR is the percentage of participants with Residual Cancer Burden (RCB)=0 as defined by established guidelines (Symmans et al. JCO 2007; M.D Anderson http://www.mdanderson.org/breastcancer\_RCB). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
次要结局
- Median Overall Survival(Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.)
- Number of Participants With a Dose Reduction(Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.)
- Hormone Receptor (HR) Status by HER2 Amplification Status(Day 0 (baseline/at study entry))
- Median Disease-Free Survival(Post-surgery follow-up of disease and survival occurs every 6 months for 5 years and annually until year 10.)
- Clinical Response Rate (Partial Response)(Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.)
- Treatment-Emergent Fatigue Rate(Adverse events are assessed every cycle of neoadjuvant therapy prior to surgery, up to approximately 18 weeks (6 cycles) from study enrollment.)
- Clinical Response Rate (Complete Response)(Evaluate upon completion of neoadjuvant therapy, up to approximately 18 weeks from study enrollment.)
- Rate of Pathologic Complete Response (pCR)(Evaluate upon completion of breast surgery, up to approximately 24 weeks from study enrollment.)
研究者
Otto Metzger, MD
Principal Investigator
Dana-Farber Cancer Institute