A Presurgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide (ODM-201)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 14
- 主要终点
- Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.
研究概览
简要总结
The purpose of this study is to evaluate the effect of short-term treatment with darolutamide on breast cancer cells (i.e., how the treatment may change the genes or proteins in breast cancer cells) and to evaluate its safety and the way it is tolerated by subjects.
The intent is to study these changes in order to have a better understanding of the potential use of darolutamide for women with EBC, know which patients are likely or unlikely to respond to this treatment, and determine how darolutamide may be combined with other anti-cancer drugs.
详细描述
This current study will enroll EBC subjects with differing breast cancer (BC) subtypes, with the intent of characterizing the molecular alterations in BC tissue before and after short-term exposure to the anti-androgen darolutamide. Studying the biological mechanisms in which darolutamide targets the androgen receptor (AR) in BC will be crucial in understanding its' potential role, as well as provide the foundation for further development of darolutamide in this disease.
TRIO030 will evaluate the following objectives: Primary -To identify the molecular alterations that occur in human BC tissue, following short-term exposure to darolutamide in female subjects with EBC; Secondary - To evaluate the safety and tolerability of short-term exposure to darolutamide in female subjects with EBC.
Design: This will be a multi-center, open-label, tissue-acquisition study involving up to 60 subjects from approximately 20 sites in North America and Europe, and will enroll EBC subjects of differing subtypes (i.e., triple negative [TNBC], ER+/HER2-, and HER2+), with the intent of characterizing the molecular alterations in BC tissue before and after short-term exposure to the anti-androgen darolutamide.
Such information may suggest that darolutamide be combined with other modalities; for example, if treatment with the drug is discovered to affect multiple signaling pathways. Molecular profiling of tumor samples before and after darolutamide treatment may permit the identification of patients likely or unlikely to respond to the agent based on the biological and molecular characteristics of their tumors.
Duration: It is recommended that the surgery date is defined prior to starting protocol treatment and then the start date of darolutamide (Day 1) will be derived as minus 14 to 21 days from the scheduled surgery date. Treatment will be taken until the day prior to surgery or when the subject is ordered to stop all oral intake (i.e., "nil per os" (npo)), which ever occurs first. If for some reason surgery takes place more than 21 days after treatment start, it is acceptable that the subject receives darolutamide for more than 21 days and up to a maximum of 35 days; subject should continue protocol treatment until the day prior to surgery, or npo is ordered. In these cases it is strongly recommended to have surgery performed as soon as possible after 21 days of treatment are completed.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed and dated PICF obtained prior to initiation of any study-specific procedure and treatment.
- •Female ≥ 18 years old.
- •Histologically proven invasive breast carcinoma (through either a core needle biopsy or an incisional biopsy) for which surgery is indicated as the primary treatment modality. Patients for which Neoadjuvant Systemic Therapy (NAST) is indicated are also eligible provided they are willing to undergo a biopsy after completing treatment with darolutamide and prior to NAST start.
- •Known ER, PgR and HER2 statuses.
- •Tumor must be confined to either the breast or to the breast and ipsilateral axilla (Note: patinets with multifocal/multicentric tumors are eligible). Patient must have (according to TNM 7th edition rules):
- •T1 with T ≥1.0cm, T2 or T3 by at least one radiographic or clinical measurement
- •Either clinically positive (N1 only) or clinically negative axillary nodes (N0)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Adequate organ function within 28 days prior to enrollment, as defined by the following criteria:
- •Hematology: Hemoglobin ≥ 9.0 g/dl; ANC ≥ 1.5 × 109/L; Platelet count ≥ 100 × 109/L
- •Liver function: ALT and AST ≤ 2.5 × ULN; Total bilirubin ≤ 1.5 × ULN (or ≤ 3 times ULN for patients with documented Gilbert's syndrome or for whom indirect bilirubin concentrations suggest an extra-hepatic source of elevation)
- •Renal function: Creatinine ≤ 2.0 × ULN
- •No more than 42 days should elapse from the day study-specific tumor sample is taken at initial diagnosis (or subsequent procedure) to the day of the first intake of darolutamide.
- •Women of childbearing potential (WoCBP)* must agree to use acceptable non-hormonal contraceptive methods of birth control from the day of the screening pregnancy test and up to 3 months after the last intake of darolutamide.
- •For WoCBP* negative serum pregnancy test within 7 days of enrollment.
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and biopsies as detailed in the protocol.
- •Note: WoCBP are any women between menarche and menopause who have not been permanently sterilized, capable of procreation. Permanent sterilization includes hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy but excludes bilateral tubal ligation/occlusion. Postmenopause is defined as: Bilateral oophorectomy; Age ≥ 60; Age < 60 and amenorrheic for ≥ 12 months in the absence of an alternative medical cause and FSH and estradiol in postmenopausal ranges.
排除标准
- •Any T0, Tis, T1 < 1.0 cm, T4; or N2-3; or M1 BC.
- •Bilateral invasive BC.
- •Patient that underwent excisional biopsy of the primary tumor.
- •Medical indication or patient desire to undergo BC surgery or start NAST prior to completing at least 14 days of treatment with darolutamide, and or refusal of patient to undergo corresponding biopsy in case NAST is planned.
- •Prior or concurrent systemic anticancer therapy for BC treatment(immunotherapy, hormonotherapy, biologic/targeted therapy, chemotherapy, investigational agents).
- •Prior or concurrent ipsilateral radiation therapy for invasive or noninvasive BC.
- •Prior or concurrent treatment or preventative use of any hormonal agent such as aromatase inhibitors (AI), fulvestrant, raloxifene, tamoxifen or other SERM, or with any other hormonal agent used for the treatment or prevention of BC or for any other indication (e.g. osteoporosis).
- •Concurrent use of ovarian hormone replacement therapy. Prior treatment should be stopped at least 28 days prior to registration.
- •Prior or concurrent treatment with AR antagonists or CYP17 enzyme inhibitor.
- •Use of other investigational drug within 28 days of enrollment.
- •Major surgery* within 28 days before enrollment.
- •Any concurrent or previous malignancy within 5 years prior to enrollment except for basal or squamous skin cancer, or carcinoma in situ of the cervix, or other non-invasive/in-situ neoplasm, all of which must have been adequately and radically treated. A patient with previous history of invasive malignancy (other than adequately and radically treated basal or squamous skin cancer) is eligible provided that she has been disease free for more than 5 years.
- •Severe or uncontrolled concurrent disease, infection or comorbidity.
- •Known active viral hepatitis, HIV or chronic liver disease.
- •Other serious illness or medical condition within 6 months before enrollment, including any of the following: Concurrent congestive heart failure NYHA Class III or IV, severe/unstable angina pectoris, myocardial infarction, uncontrolled hypertension, coronary/peripheral artery bypass graft, high-risk uncontrolled arrhythmias, stroke.
- •Any contraindication to oral agents or gastrointestinal disorder or procedure which expects to interfere significantly with absorption of protocol treatment.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Known allergy to darolutamide or any of the excipients.
- •Pregnant or lactating darolutamide. * Note: Major surgery defined as requiring a general anesthesia or respiratory assistance; involving openings into the great cavities of the body, organs removed, or normal anatomy altered; implying risks of severe hemorrhage; implying risk for life of the patient or severe disability.
研究组 & 干预措施
Presurgical Molecular Assessment
Oral 300 mg darolutamide tablet; dose of 600 mg (2 x 300 mg tablets) b.i.d.
干预措施: darolutamide (Drug)
结局指标
主要结局
Identifying Molecular Alterations in Breast Cancer Tissue Tumor Samples Following Short-Term Preoperative Exposure to Darolutamide in Female Patients Wit Early Breast Cancer.
时间窗: 1 year, 6 months
Androgen Receptor (AR) was assessed on the collected samples.
次要结局
- Number of Participants With Treatment-related Adverse Events (TEAE) as Assessed by CTCAE v4.03(1 year, 6 months)