RADIANT Study: Pre-op Radiation With Abemaciclib Andletrozole in Early Stage Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 15
- 试验地点
- 4
- 主要终点
- Safety and tolerability of the combination of abemaciclib and radiation as assessed by adverse events (AEs). Using Common Terminology Criteria for Adverse Events (CTCAE v5.0)
研究概览
简要总结
This phase 1b study investigates the safety and feasibility of combining pre-operative radiation therapy with Cyclin-Dependent Kinase 4 (CDK4/6) inhibitors in participants with hormone receptor positive/HER2 negative (HR+/HER2-) breast cancer. The study aims to assess the benefits of concurrent use of these treatments in a specific participant population, focusing on their safety and tolerability. The hypothesis is that the combination therapy will be well-tolerated, providing valuable insights into its effectiveness for future clinical applications.
详细描述
In this phase 1b study, researchers will conduct a comprehensive investigation into the concurrent administration of pre-operative radiation therapy and CDK4/6 inhibitors in a carefully selected participant population diagnosed with hormone receptor positive/HER2 negative (HR+/HER2-) breast cancer. The study aims to elucidate the safety and feasibility of this combination therapy. Participants will undergo rigorous evaluation and monitoring to assess the potential synergistic effects and adverse reactions resulting from the simultaneous use of radiation and CDK4/6 inhibitors. Detailed clinical assessments, imaging studies, and laboratory analyses will be performed to monitor treatment response and any associated side effects.
The study hypothesizes that this combination therapy will be well-tolerated, paving the way for further investigations into its efficacy. By closely examining the outcomes and tolerability of this treatment approach, researchers aim to contribute valuable data to the understanding of novel therapeutic strategies for HR+/HER2- breast cancer. The detailed analysis of participant responses and safety profiles in this study will provide crucial insights for optimizing future clinical interventions and improving outcomes for individuals diagnosed with this specific breast cancer subtype.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically and/or cytologically confirmed diagnosis of invasive (ductal, lobular or mixed histology), Clinically inapparent tumor that is not palpable. (cT1-T2N0)disease. Minimum tumor size of 1.5 cm
- •Expression of ER or progesterone receptors (PR)and negative expression of HER2 per American Society of Clinical Oncology, (ASCO) Common Alerting Protocol (CAP) guidelines
- •Oncotype diagnosis (DX) Breast Recurrence score of less than 25 on core biopsy specimen
- •Post-menopausal status defined:
- •age <60 with amenorrhea for at least 12 months in the absence of prior chemotherapy, tamoxifen, toremifene, or ovarian suppression and estradiol and FSH (follicle stimulating hormone) in postmenopausal range.
- •No clinical suspicion of metastasis disease
- •Eastern Cooperative Oncology Group (ECOG) performance status of follicle stimulating hormone (PFS) ≤2
- •Eligible to undergo surgery, either lumpectomy or mastectomy for local treatment of the breast cancer
- •Able to swallow oral medications
- •Adequate organ function for all of the following:
- •Absolute Neutrophil (ANC) >1.5 x 10/L Platelets >100 x 10/L Hemoglobin >8 g/dL - May receive erythrocyte transfusions to achieve this level Total Bilirubin <1.5 x Upper Limit of Normal (ULN) Alanine Aminotransferase (ATL) and Aspartate Aminotransferase (AST) <3 x ULN
- •HR positive/HER2 -negative breast cancers are allowed as long as no other exclusions exist
排除标准
- •History of ipsilateral breast cancer
- •Prior treatment with CDK4/6 inhibitors or aromatase inhibitors
- •History of chest wall or ipsilateral breast radiation
- •Inflammatory breast cancer
- •Needs neoadjuvant chemotherapy
- •Presence of distant metastatic disease
- •Contraindication for surgery
- •Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg)
- •Any condition including the presence of laboratory abnormalities, which, in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study
- •Life expectancy < 12 weeks
- •History of allergy or hypersensitivity to any of the study drugs
- •Any significant medical condition, laboratory abnormality, or psychiatric illness
- •Serious and/or uncontrolled preexisting medical condition
- •Has had major surgery within 14 days prior to enrollment
- •Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research
- •Has active systemic bacterial infection
- •Personal 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), or sudden cardiac arrest
研究组 & 干预措施
Combined Pre-Operative Therapy with Abemaciclib, Letrozole, and Radiation in HR+/HER2- Breast Cancer
Part A:
- 28-day treatment cycle based on abemaciclib
- Abemaciclib 150mg BID (twice a day).
- Letrozole 2.5mg daily and Abemaciclib 150mg twice a day for three cycles prior to undergoing radiation therapy.
- On-treatment biopsy conducted between cycle 3, day 16, and cycle 4, day 1.
- This occurs two weeks prior to transitioning to Part B.
Dose Level 0 150mg Twice daily with at least 6 hours between doses Dose Level 1 100mg Twice daily with at least 6 hours between doses Dose Level 2 50mg Twice daily with at least 6 hours between doses
Part B:
- Continue treatment from Part A, 28-day cycle based on abemaciclib.
- Abemaciclib 150mg BID (twice a day) with letrozole 2.5mg daily.
- Part B focuses on the administration of radiation therapy following the three cycles of combined abemaciclib and letrozole.
- Targeted radiation treatment.
Part C:
- Two cycles of abemaciclib, 150mg twice a day.
- Letrozole 2.5mg daily.
Part D:
Surgery
干预措施: Abemaciclib (Drug)
Combined Pre-Operative Therapy with Abemaciclib, Letrozole, and Radiation in HR+/HER2- Breast Cancer
Part A:
- 28-day treatment cycle based on abemaciclib
- Abemaciclib 150mg BID (twice a day).
- Letrozole 2.5mg daily and Abemaciclib 150mg twice a day for three cycles prior to undergoing radiation therapy.
- On-treatment biopsy conducted between cycle 3, day 16, and cycle 4, day 1.
- This occurs two weeks prior to transitioning to Part B.
Dose Level 0 150mg Twice daily with at least 6 hours between doses Dose Level 1 100mg Twice daily with at least 6 hours between doses Dose Level 2 50mg Twice daily with at least 6 hours between doses
Part B:
- Continue treatment from Part A, 28-day cycle based on abemaciclib.
- Abemaciclib 150mg BID (twice a day) with letrozole 2.5mg daily.
- Part B focuses on the administration of radiation therapy following the three cycles of combined abemaciclib and letrozole.
- Targeted radiation treatment.
Part C:
- Two cycles of abemaciclib, 150mg twice a day.
- Letrozole 2.5mg daily.
Part D:
Surgery
干预措施: Letrozole (Drug)
结局指标
主要结局
Safety and tolerability of the combination of abemaciclib and radiation as assessed by adverse events (AEs). Using Common Terminology Criteria for Adverse Events (CTCAE v5.0)
时间窗: From baseline, every six months, to five years
The outcome measure aims to characterize the safety and toxicity profile of the study treatment by assessing the occurrence and severity of adverse events (AEs) as measured using the CTCAE v.5. The CTCAE v.5 utilizes a standardized grading scale to assess the severity of adverse events. The scale consists of grades ranging from 1 to 5, with each grade corresponding to a specific level of severity. The grades are: Grade 1 Mild Event is asymptomatic or mild, requiring minimal or no medical intervention. Grade 2 Moderate Event minimal to moderate interference with daily activities, and some medical intervention. Grade 3 Severe Event causes significant interference with daily activities, and medical intervention or treatment is required. Grade 4 Life-threatening or disabling Event poses immediate risk to life or function, requiring urgent medical intervention or treatment. Grade 5 Death Event results in death related to the adverse event.
次要结局
- Rate of breast-conserving surgery measured with with a 95% confidence interval for proportions(From baseline, every six months, to five years)
- Two year invasive disease-free survival (DFS) rate(From baseline, every six months, to five years)
- Rates of residual cancer burden (RCB) as a proportion with 95% confidence interval(From baseline, every six months, to five years)
- Clinical efficacy of the study treatment regimen measured by Rates of Residual Cancer Burden (RCB).(From baseline, every six months, to five years)
- Rate of post-operative complications measured by descriptive statistics(From baseline, every six months, to five years)
研究者
Mridula George, MD
Assistant Professor of Medicine
Rutgers, The State University of New Jersey