A Multi-Institutional Double-Blind Phase II Study Evaluating Response and Surrogate Biomarkers to Carboplatin and Nab-Paclitaxel (CP) With or Without Vorinostat as Preoperative Chemotherapy in HER2-negative Primary Operable Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 68
- 试验地点
- 5
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help carboplatin and paclitaxel albumin-stabilized nanoparticle formulation work better by making tumor cells more sensitive to the drugs. Giving chemotherapy with or without vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
PURPOSE: This randomized phase II trial is studying how well giving carboplatin together with paclitaxel albumin-stabilized nanoparticle formulation works with or without vorinostat in treating women with breast cancer that can be removed by surgery.
详细描述
OBJECTIVES:
Primary
- To determine pathological complete response (pCR) rates in patients with HER2-negative primary operable breast cancer treated with neoadjuvant therapy comprising carboplatin and paclitaxel albumin-stabilized nanoparticle formulation (CP) with vs without vorinostat.
Secondary
- To evaluate the safety of these regimens in these patients.
- To estimate clinical complete response (cCR) rates in patients treated with these regimens.
- To correlate baseline and change (day 15) in surrogate uptake values (SUV) on FDG-PET with pathological and clinical response in patients treated with these regimens, and to determine what percent of women with ≥ 25% or ≥ 50% reduction in SUV on day 15 achieve a pCR and a cCR to CP with vs without vorinostat.
- To correlate baseline and change in markers of proliferation with pathological and clinical response in patients treated with these regimens.
- To evaluate long term outcomes (e.g., recurrence of the breast cancer, development of a new cancer, or death) for patients treated with these regimens.
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
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed infiltrating ductal breast cancer by core needle biopsy
- •Mixed ductal and lobular disease allowed
- •Infiltrating lobular cancer allowed in the run-in portion only
- •Unresected, clinically measurable disease, meeting 1 of the following clinical staging criteria:
- •T2, T3, or T4 lesion, any N, M0
- •T1c, N1-3,M0
- •Patients with skin metastases to the ipsilateral breast for whom chemotherapy is planned prior to definitive surgery are eligible for the primary study portion
- •HER2-negative disease
- •Hormone receptor status* meeting 1 of the following criteria:
- •Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative
- •ER-positive (grade II or III) and PR-positive or PR-negative NOTE: *Any ER or PR status for the run-in portion
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-1
- •Menopausal status not specified
- •ANC ≥ 1,500/mm³
- •Platelet count ≥ 150,000/mm³
- •Hemoglobin ≥ 9 g/dL
- •Creatinine ≤ 1.5 times the upper limit of normal (ULN)
- •Creatinine clearance ≥ 50 mL/min
- •Total bilirubin normal
- •AST(SGOT) and ALT(SGPT) ≤ 2.5 times (ULN)
- •alkaline phosphatase ≤ 2.5 times ULN
- •PT such that INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin) and PTT ≤ ULN
- •Adequate cardiac function defined as no evidence of PR prolongation or AV block on baseline electrocardiogram (ECG)
- •Willing to use effective, non-hormonal contraception while on treatment and for at least 3 months thereafter
- •Not pregnant or nursing
- •No pre-existing peripheral neuropathy ≥ grade 2
- •No history of severe hypersensitivity reaction to any drug formulated with polysorbate 80 or to E. coli-derived products
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
- •No medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on this therapy
- •PRIOR CONCURRENT THERAPY:
- •At least 4 weeks since prior valproic acid or other histone deacetylase inhibitor
- •No prior chemotherapy, radiotherapy, or endocrine therapy for this cancer
- •Prior tamoxifen or raloxifene or another agent for prevention of breast cancer allowed as long as the patient has discontinued the treatment ≥ 1 month prior to baseline study biopsy
- •No systemic treatment for prior cancer within the past 5 years (primary study portion)
- •No prior or ongoing systemic treatment for this cancer (primary study portion)
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent histone deacetylase inhibitor
- •No other concurrent chemotherapy, antiestrogen therapy, radiotherapy, or other investigational systemic therapy
- •No other concurrent biologic therapy
- •No other concurrent investigational drugs
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: placebo (Other)
Arm I
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Arm I
Patients receive carboplatin IV and paclitaxel albumin-stabilized nanoparticle formulation IV on day 1 and an oral placebo on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Arm II
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: carboplatin (Drug)
Arm II
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: paclitaxel albumin-stabilized nanoparticle formulation (Drug)
Arm II
Patients receive carboplatin and paclitaxel albumin-stabilized nanoparticle formulation as in arm I and oral vorinostat on days 1-3. Treatment repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: Time of breast cancer surgery
The primary end point was pCR, defined as no viable invasive cancer in breast and axilla. All other cases were defined as non-pCR. The pCR rate was determined in each arm separately by performing an intent-to-treat (ITT) analysis of all randomized patients. Patients with unknown pCR status were considered non-responders. Computation of associated 90% confidence intervals did not account for the sequential design.
次要结局
- Safety as Measured by Number of Participants Who Experience Adverse Events(up to 30 days post-treatment)
- Number of Participants With Clinical Complete Response (cCR)(12 weeks)
- Change in Standard Uptake Value (SULmax) From Baseline to Day 15 on FDG-PET(Baseline and day 15)
- Absolute Change From Baseline in Ki-67(Change from baseline to Cycle 1-Day 15)
- Change in Cumulative Methylation Index (CMI)(Change from baseline to Day 15)
- Cumulative Methylation Index (CMI) at Day 15(Day 15)
- Number of Participants Who Experience Death During Treatment(Up to 12 weeks)
- Number of Participants Who Develop New Cancer(Up to death of last participant (duration unknown))
- Number of Participants With Recurrence of Breast Cancer(Up to death of last participant (duration unknown))
- Overall Survival(Up to death of last participant (duration unknown))