PREDIX Luminal A - Neoadjuvant Response-guided Treatment of Slowly Proliferating Hormone Receptor Positive Tumors. Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clinical and Radiological Response
研究概览
简要总结
The purpose of this neoadjuvant trial is to evaluate efficacy and toxicity of the cdk 4/6 inhibitor palbociclib when added to standard endocrine treatment. Initially, patients receive endocrine treatment for 4 weeks. In case of decrease of proliferation (Ki67) patients are then randomized between either continuous endocrine therapy (arm A) or the same treatment with addition of palbociclib (arm B). Patients with no change of proliferation are allocated to endocrine treatment + palbociclib without randomization (arm C). During the 12-weekly treatment period, clinical and radiological evaluations are performed repeatedly. Switch between the treatment arms A and B is allowed in case of lack of response or due to toxicity. A translational subprotocol is a mandatory part of the study protocol, except for use of PET-CT evaluations.
详细描述
Pre- or perimenopausal women are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women). Postmenopausal women receive an aromatase inhibitor.This treatment is given for 4 weeks. In cases with uncertain menopausal status (previous hysterectomy and equivocal gonadotropins), postmenopause age limit is defined as 55 years or older.
Ki67 is determined by FNA or core biopsy before start and after 2 weeks of treatment. After the initial 4-week period, patients with signs of response in terms of decrease of Ki67 by ≥20% are randomized to endocrine treatment either alone or in combination with the cdk 4/6 inhibitor palbociclib (arm A and B). Patients with tumors with stable disease, defined as <20% decrease or increase of Ki67 and without radiological indication of tumor progression at the 4-week evaluation are offered continuous endocrine treatment with the addition of palbociclib (arm C).
Dose regimen after 4 weeks of endocrine pretreatment:
Arm A: Pre- or perimenopausal women are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women). Postmenopausal women receive an aromatase inhibitor. The preoperative treatment is continued for further 12 weeks, provided that re-evaluation after 6 and 10 weeks of the preoperative treatment does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option.
Arm B: Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, if re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option.
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
- None
入排标准
- 年龄范围
- 41 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Female patients with non-lobular breast cancer confirmed by histology
- •Tumor and blood samples available. Luminal A type confirmed by immunohistochemistry with ER and PR positive ≥50% and the proliferation marker Ki 67 <20% and not HER2 amplified
- •Age older than 40 years
- •Primary breast cancer >20mm without lymph node metastases
- •Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
- •ECOG performance status 0-1
排除标准
- •Metastases, including node metastases in the ipsilateral and/or contralateral thoracic region or in the mediastinum
- •Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix
- •Age ≤40 years
- •Lobular carcinoma
- •Patients in child-bearing age without adequate contraception
- •Pregnancy or lactation
- •Severe medical or psychiatric disorders where the study treatment or study procedures carry increased risk of deterioration of health status
研究组 & 干预措施
A: Endocrine treatment
Pre- or perimenopausal women are treated with tamoxifen, alternatively with an LHRH analogue in combination with an aromatase inhibitor (only women); postmenopausal women receive an aromatase inhibitor. The preoperative treatment is continued for further 12 weeks, provided that re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option
干预措施: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin (Drug)
B: Endocrine treatment + palbociclib
Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, provided that re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option
干预措施: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin (Drug)
B: Endocrine treatment + palbociclib
Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, provided that re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option
干预措施: Palbociclib (Drug)
C: Endocrine treatment + palbociclib
Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, if re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option
干预措施: Tamoxifen or Aromatase Inhibitor or Aromatase Inhibitor + goserelin (Drug)
C: Endocrine treatment + palbociclib
Patients receive the same endocrine treatment as in arm A together with palbociclib 125 mg orally days 1-21, followed by a 7-days rest period. The combined treatment is continued for further 12 weeks, if re-evaluation after 6 weeks, week 10 of the preoperative treatment, does not indicate progression. Upon progression (PD), individualized management, preferentially surgery, is the primary option
干预措施: Palbociclib (Drug)
结局指标
主要结局
Clinical and Radiological Response
时间窗: After 16 weeks of preoperative treatment
Clinical evaluations by use of calliper, radiological evaluations with mammography and ultrasound after 4, 10 and 16 weeks, PET-CT after 10 weeks of treatment, compared with baseline measurements
次要结局
- Overall Survival(From date of surgery until 60 months past surgery)
- Health-related Quality of Life(From start of study treatment until termination, and then annually during the 60 months of postoperative follow-up period)
- Breast Cancer-specific Survival(From date of surgery until 60 months past surgery)
- Incidence of treatment-emergent adverse events [Safety and Tolerability](From start of treatment until 28 days after termination of treatment. Delayed toxicity is reported until 60 months follow-up)
- Disease-free Survival(From date of surgery until 60 months past surgery)
- Immunohistochemical characteristics(Before start, during treatment and at the date of operation)
- Thymidine kinase (TK1) activity during study treatment(Before start and until termination of the preoperative treatment)
- Pathological Evaluation of Tumor Response(From date of surgery up to 4 weeks)
- Biological characteristics of tumors exposed to targeted treatment of early breast cancer(Before start and during treatment, at surgery, and then annually during the 60 months of postoperative follow-up period)
- Drug metabolism during study treatment(Four and ten weeks after start of the preoperative treatment)
研究者
Thomas Hatschek
Sen. Consultant, MD, PhD, Assoc. professor
Karolinska University Hospital