Window Trial of Abemaciclib for Surgically Resectable, Chemotherapy-Resistant, Triple Negative Breast Cancer (a BEAUTY Study*)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Mayo Clinic
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6
研究概览
简要总结
This phase II trial studies how well abemaciclib works in treating patients with triple negative breast cancer that can be removed by surgery (resectable) and does not respond to treatment with chemotherapy alone, or in combination with pembrolizumab. Abemaciclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant triple negative breast cancer (TNBC) patients following neoadjuvant chemotherapy regimen without the addition of pembrolizumab (Cohort A).
II. To examine the effects of abemaciclib on the CD8/FOXP3 ratio in chemotherapy resistant TNBC patients following a neoadjuvant chemotherapy regimen with the addition of pembrolizumab (Cohort B).
SECONDARY OBJECTIVES for Cohort A and Cohort B Independently:
I. Assess abemaciclib toxicities. II. To examine the effects of abemaciclib on the percentage of vimentin expressing invasive cancer cells
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Women of age >=18 years
- •PRE-REGISTRATION: Clinical T1-4, N0-3, M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy) by American Joint Committee on Cancer (AJCC) staging version
- •Note: Benign breast disease, lobular carcinoma in situ (LCIS) or ductal carcinoma in situ (DCIS) in the ipsilateral or contralateral breast is allowed.
- •Note: Additional ipsilateral or contralateral invasive breast cancer is allowed. The index lesion is the largest triple-negative, chemotherapy-resistant lesion.
- •PRE-REGISTRATION: Histological confirmation of triple negative invasive breast cancer (defined as estrogen receptor [ER] =< 10%, progesterone receptor [PR] =< 10% and HER2 not amplified by in situ hybridization [ISH] or immunohistochemistry [IHC] 0/1) at diagnosis.
- •PRE-REGISTRATION: Cohort A: CLOSED TO PRE-REGISTRATION and REGISTRATION as of protocol amendment 6 (04/14/2023) Neoadjuvant chemotherapy (NAC) with one of the following regimens that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
- •Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC)
- •Note: Carboplatin may be added to these regimens
- •AC or EC or FEC followed by docetaxel or paclitaxel
- •Note: Carboplatin may be added to these regimens
- •Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
- •Docetaxel in combination with cyclophosphamide (TC) (for patients who are not candidates for anthracyclines)
- •Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel) (for patients who are not candidates for anthracyclines)
- •PRE-REGISTRATION: Cohort B: Neoadjuvant chemotherapy (NAC) with one of the following regimens in combination with pembrolizumab that was not discontinued early due to intolerability with less than 50% of planned treatment given due to disease progression or patient request:
- •Paclitaxel or docetaxel followed by one of the following: the combination of doxorubicin and cyclophosphamide (AC); the combination of epirubicin and cyclophosphamide (EC) or the combination of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) Note: Carboplatin may be added to these regimens
- •AC or EC or FEC followed by docetaxel or paclitaxel [Note: Carboplatin may be added to these regimens]
- •Docetaxel in combination with doxorubicin and cyclophosphamide (TAC)
- •Docetaxel in combination with cyclophosphamide (TC)
- •Carboplatin or cisplatin in combination with a taxane (paclitaxel, docetaxel, or nab-paclitaxel)
- •PRE-REGISTRATION: Residual lesion/enhancement seen in the breast on breast imaging performed after completion of NAC.
- •PRE-REGISTRATION: Able to swallow oral medication.
- •PRE-REGISTRATION: Willing to undergo biopsy for research.
- •PRE-REGISTRATION: Willing to provide tissue and blood samples for correlative research purposes.
- •PRE-REGISTRATION: Willing to stop use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
- •PRE-REGISTRATION: Provide written informed consent.
- •REGISTRATION: Registration must occur =< 56 days after last dose of NAC.
- •REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or
- •REGISTRATION: COHORT B GROUP 4 ONLY: The following laboratory values obtained after completion of NAC but =< 14 days prior to registration:
- •REGISTRATION: COHORT B GROUP 4 ONLY: Absolute neutrophil count (ANC) >= 1500/mm^
- •REGISTRATION: COHORT B GROUP 4 ONLY: Platelets (PLT) >= 100,000/mm^
- •REGISTRATION: COHORT B GROUP 4 ONLY: Hemoglobin (HgB) >= 8.0 g/dL.
- •REGISTRATION: COHORT B GROUP 4 ONLY: Total bilirubin =< 1.5 x upper limit of normal (ULN).
- •REGISTRATION: COHORT B GROUP 4 ONLY: Aspartate transaminase (AST) serum glutamic oxaloacetic transaminase (SGOT) =< 3 x ULN.
- •REGISTRATION: COHORT B GROUP 4 ONLY: Alanine transaminase (ALT) serum glutamate pyruvate transaminase (SGPT) =< 3 x ULN.
- •REGISTRATION: COHORT B GROUP 4 ONLY: Serum creatinine =< 1.5 x ULN.
- •REGISTRATION: GROUP 2 ONLY: Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only.
排除标准
- •PRE-REGISTRATION: History of deep venous thrombosis (DVT) or pulmonary embolisms (PE) =< 12 months prior to preregistration; OR Active DVT and/or PE requiring anti-coagulant therapy.
- •NOTE: Patients who are on anti-coagulant therapy for maintenance are eligible as long as the DVT and/or PE was > 12 months prior to enrollment and there is no evidence for active thrombosis (either DVT or PE).
- •NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
- •PRE-REGISTRATION: Prior treatment with CDK 4/6 inhibitors (e.g. palbociclib, ribociclib, abemaciclib, etc.)
- •PRE-REGISTRATION: Prior treatment with radiation for this breast cancer.
- •PRE-REGISTRATION: Prior incisional or excisional breast biopsy for this cancer.
- •PRE-REGISTRATION: Any contraindications to pre-registration biopsy (such as bleeding diatheses, etc.).
- •PRE-REGISTRATION: Receiving any investigational agent which would be considered as a treatment for the primary neoplasm.
- •PRE-REGISTRATION: Other active malignancy =< 3 years prior to registration.
- •EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
- •NOTE: If there is a history of prior malignancy, they must not be receiving another specific treatment for prior malignancy.
- •PRE-REGISTRATION: Biopsy proven Stage IV breast cancer.
- •PRE-REGISTRATION: Serious pre-existing medical conditions that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance < 30 ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea).
- •PRE-REGISTRATION: History of any of the following conditions:
- •Syncope of cardiovascular etiology.
- •Ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation).
- •Sudden cardiac arrest.
- •NOTE: Patients on anticoagulation are eligible; however peri-biopsy and peri-surgical management of anticoagulation is per the institutional standard of care.
- •REGISTRATION: COHORT B GROUP 4: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- •Pregnant persons.
- •Nursing persons.
- •Persons of childbearing potential who are unwilling to employ adequate contraception.
- •REGISTRATION: COHORT B GROUP 4: Failure to recover to grade 1 or lower from effects of neoadjuvant chemotherapy.
- •Exceptions: Residual alopecia and grade 2 peripheral neuropathy are allowed.
- •REGISTRATION: COHORT B GROUP 4: Concurrent use of strong and moderate inducers and/or strong inhibitors of cytochrome P450 3A =< 7 days prior to registration.
- •REGISTRATION: COHORT B GROUP 4: Known infections as follows (NOTE: Screening is not required for enrollment):
- •Active systemic bacterial infection requiring intravenous antibiotics.
- •Active fungal infection (requiring intravenous or oral antifungal treatment).
- •Detectable viral infections (e.g. known human immunodeficiency virus [HIV], known active hepatitis B or C).
- •REGISTRATION: COHORT B GROUP 4: Concurrent use of chemotherapy, radiotherapy, immunotherapy, or other components of neoadjuvant treatment.
- •NOTE: Patients must complete all elements of NAC ≥21 days prior to starting abemaciclib.
研究组 & 干预措施
Cohort A Group 1; Cohort B Group 3 (surgery)
Patients undergo standard of care surgical resection.
干预措施: Therapeutic Conventional Surgery (Procedure)
Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)
Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.
干预措施: Abemaciclib (Drug)
Cohort A Group 2; Cohort B Group 4 (abemaciclib, surgery)
Patients receive abemaciclib PO BID on days 1-14 or days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgical resection no later than 12 weeks after the last dose of neoadjuvant chemotherapy.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Proportion of patients who have a CD8/FOXP3 ratio < 1.6 in their residual tumors after neoadjuvant chemotherapy (NAC) that convert to CD8/FOXP3 ratio >= 1.6
时间窗: Up to 21 days
A Simon optimum two stage phase II clinical trial design was chosen to test the null hypothesis that the rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is =\< 5% against the alternative that rate of conversion to post-abemaciclib CD8/FOXP3 ratio of 1.6 or more is \>= 20% with the target probability of a type I error and probability of a type II error set to 0.10. The probability of terminating after the first stage is 0.736, if the null hypothesis is true. A 90% confidence interval for this rate of conversion will be constructed using the Duffy-Santner approach taking into account the sequential nature of the study
次要结局
- Incidence of adverse events(Up to 60 days)
- Impact of length of treatment(Up to 60 days)
- Changes in vimentin expression(Up to 60 days)