NCT01723774进行中（未招募）2 期
A Phase II Trial of Neoadjuvant PD 0332991, a Cyclin-Dependent Kinase (Cdk) 4/6 Inhibitor, in Combination With Anastrozole in Women With Clinical Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 84
- 试验地点
- 8
- 主要终点
- Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)
研究概览
简要总结
A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67>10% compared to historical control.
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
- •Pre-registration PIK3CA Mutant Inclusion
- •Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
- •Female ≥18 years of age
- •ECOG performance status of 0, 1 or 2
- •Life expectancy > 4 months
- •Premenopausal, patient must be willing to comply with pregnancy requirements
- •Adequate organ and marrow function
- •leukocytes ≥ 3,000/mcL
- •absolute neutrophil count ≥ 1,500/mcL
- •platelets ≥ 100,000/mcL
- •total bilirubin ≤ ULN
- •AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- •Creatinine ≤ ULN
- •Able to understand and willing to sign an IRB-approved written informed consent document
- •Prior treatment of this cancer including: surgery, radiation, chemotherapy, biotherapy, hormonal therapy, investigational agent prior to study entry
- •Receiving any investigational agents
- •Prior therapy with any Cdk4 inhibitor
- •Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
- •Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant/nursing
- •Unwilling to employ adequate contraception
- •Known HIV-positive on combination antiretroviral therapy
- •Evidence of inflammatory cancer
- •Known metastatic disease
- •Current use of anticoagulation therapy
- •Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
- •Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
- •Corrected QT interval >470 msec
- •Registration PIK3CA Mutant Inclusion The criteria below must be met in addition to the pre-registration criteria, except treatment with endocrine therapy for this cancer is allowed prior to registration
- •PIK3CA mutant cohort: tumor PIK3CA mutation present
- •Premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration
排除标准
- •below must be met in addition to the pre-registration criteria -Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)
- •PIK3CA Wild Type Inclusion
- •Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
- •For the PIK3CA wild type cohort: tumor PIK3CA mutation absent. Note that if a patient did not have sufficient research tissue for PIK3CA sequencing at pre-registration or if PIK3CA sequencing result is delayed, she could be registered and enrolled on the PD991 trial without assigning to a particular cohort at the time of enrollment. PIK3CA sequencing will be performed in the future on tumors collected at subsequent time points to assign the treatment cohort or when the PIK3CA sequencing data is available
- •For the endocrine resistant cohort: Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. Note that prior neoadjuvant endocrine therapy could include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant) alone or in combination, or endocrine therapy in combination with any investigational agent that is not a Cdk 4/6 inhibitor
- •*Patients who had a Day 17 Ki67 > 10% from the NCI9170 trial are eligible for the endocrine resistant cohort
- •Female >18 years of age
- •ECOG performance status of 0, 1 or 2
- •Life expectancy > 4 months
- •If premenopausal, patient must be willing to comply with pregnancy requirements
- •Adequate organ and marrow function:
- •leukocytes ≥ 3,000/mcL
- •absolute neutrophil count ≥ 1,500/mcL
- •platelets ≥ 100,000/mcL
- •total bilirubin ≤ ULN
- •AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- •Creatinine ≤ ULN
- •In premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration.
- •Able to understand and willing to sign an IRB-approved written informed consent document
- •Prior treatment of this cancer including: Surgery, Radiation therapy, Chemotherapy, Biotherapy, Hormonal therapy, Investigational agent prior to study entry
- •Receiving any other investigational agents
- •Prior therapy with any Cdk4 inhibitor
- •Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
- •Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant/nursing
- •Unwilling to employ adequate contraception
- •Known HIV-positive on combination antiretroviral therapy
- •Evidence of inflammatory cancer
- •Known metastatic disease
- •Current use of anticoagulation therapy
- •Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
- •Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
- •Corrected QT interval >470 msec
- •Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)
- •Endocrine Resistant Inclusion
- •Clinical T2-T4c at diagnosis or screening, any N, M0 invasive ER+ (Allred Score at least 3 or > 1% ER positivity) and HER2 negative (0 or 1+ by IHC or FISH negative or equivocal) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive breast cancer that is ER pos, HER2 neg or equivocal or DCIS in the contralateral breast are eligible; multi-focal diseases are not excluded. The dominant lesion will be followed per protocol
- •Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. If Ki67 is > 10% by local testing, the Ki67 slide and H&E slide need to be reviewed by the study pathologist to confirm eligibility (discuss with Study Chair). For patients external to Washington University, please contact the Washington University coordinator by email so that a screening ID# can be assigned prior to shipment of the slides
- •Female ≥ 18 years of age
- •ECOG performance status of 0, 1 or 2
- •Pre- or post-menopausal women are eligible. If premenopausal, patient must be willing to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian suppression during the study
- •Adequate organ and marrow function:
- •Leukocytes ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Total bilirubin ≤ ULN
- •AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
- •Creatinine ≤ ULN
- •Able to understand and willing to sign an IRB-approved written informed consent document
- •Prior treatment of this cancer including: Surgery, Radiation, Chemotherapy
- 另有 40 项未显示
研究组 & 干预措施
Arm 1: PIK3CA Wild Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Surgery (standard of care) (Procedure)
Arm 1: PIK3CA Wild Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Tumor biopsy (Procedure)
Arm 2: PIK3CA Mutant Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Surgery (standard of care) (Procedure)
Arm 2: PIK3CA Mutant Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Tumor biopsy (Procedure)
Arm 3: Endocrine Resistant Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Surgery (standard of care) (Procedure)
Arm 3: Endocrine Resistant Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Tumor biopsy (Procedure)
Arm 1: PIK3CA Wild Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Goserelin (Drug)
Arm 1: PIK3CA Wild Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Anastrozole (Drug)
Arm 2: PIK3CA Mutant Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Goserelin (Drug)
Arm 2: PIK3CA Mutant Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Anastrozole (Drug)
Arm 3: Endocrine Resistant Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Goserelin (Drug)
Arm 3: Endocrine Resistant Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: Anastrozole (Drug)
Arm 1: PIK3CA Wild Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: PD0332991 (Drug)
Arm 3: Endocrine Resistant Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: PD0332991 (Drug)
Arm 2: PIK3CA Mutant Type Cohort
Experimental
- Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
- Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
- Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
- Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
- Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
干预措施: PD0332991 (Drug)
结局指标
主要结局
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)
时间窗: At cycle 1 day 15 (2 weeks)
Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)
时间窗: At cycle 1 day 15 (2 weeks)
Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
次要结局
- Change in Ki67 Level of Tumor Specimens(Pre-treatment and cycle 1 day 15)
- Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)(At cycle 1 day 15 (2 weeks))
- Number of Participants With Complete Cell Cycle Arrest(Cycle 1 day 1 and cycle 1 day 15 (2 weeks))
- Clinical Response Rate(16 weeks)
- Radiologic Response Rate(At the end of cycle 4 prior to surgery (estimated to be 16 weeks))
- Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events(From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy)
- Number of Participants With a PEPI-0 Score(At the time of surgery (estimated to be 5 months))
- Change in Ki67 Level of Tumor Specimens(Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days))
- Number of Participants With Pathologic Complete Response (pCR)(At the time of surgery (estimated to be 5 months))
- Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event(From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 2 years))
- Overall Survival(5 years)
- Relapse-free Survival(5 years)
- Local Recurrence Rate(5 years)
- Regional Recurrence Rate(5 years)
- Distant Recurrence Rate(5 years)
- Rate of Second Primary Breast Cancer(5 years)
- Rate of Second Primary Cancer (Non-breast)(5 years)
研究者
研究点 (8)
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