A Phase I Study of Rucaparib Administered Concurrently With Postoperative Radiotherapy in Patients With Triple Negative Breast Cancer With an Incomplete Pathologic Response Following Neoadjuvant Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 8
- 主要终点
- Dose Limiting Toxicities
研究概览
简要总结
The purpose of this study is to test the safety of a study drug called Rucaparib, administered in combination with the type of radiation therapy that is usually given to women with your form of breast cancer.
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
- •Female, ≥ 18 years of age.
- •Non-metastatic, histologically or cytologically-confirmed TNBC (defined as ER <1%, PR <1%, her-2-neu 0-1+ by IHC or FISH-negative or as per MD discretion), with evidence of residual disease in the breast or lymph nodes after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
- •Non-metastatic, histologically or cytologically-confirmed hormone-receptor positive, Her2/neu negative breast cancer (defined as ER >1% or PR >1% AND Her-2/neu 0-1+ by IHC or FISH-negative, or as per MD discretion), with evidence of residual grade 3 invasive breast cancer AND either 1) >5 cm of residual disease in the breast OR 2) ≥ 4 axillary LNs in the axilla after neoadjuvant chemotherapy, at the time of definitive surgical treatment.
- •Definitive surgical treatment with breast-conserving surgery or mastectomy and axillary lymph node evaluation.
- •At least 6-month life expectancy, ECOG Performance status <
- •Willingness to discontinue any cytotoxic chemotherapeutic agents, and biologic therapy at least 2 weeks prior to the start of RT.
- •Adequate organ function (assessed within 30 days prior to initiation of protocol treatment, unless otherwise indicated) as follows:
- •Absolute Neutrophil Count (ANC) ≥1500/mm^3
- •Platelet Count ≥100,000/mm^3
- •Hemoglobin ≥9.0 g/dL (after transfusion if required) Renal Function
- •Creatinine Serum ≤ 1.5 mg/dL or Creatinine Clearance ≥ 45 mL/min^a Hepatic Function
- •Bilirubin ≤ 1.5 mg/dL
- •Aspartate Aminotransferase (AST) ≤ 2.5 x ULN^b
- •Alanine Aminotransferase (ALT) ≤ 2.5 x ULN ULN = upper normal limit of institution's normal range
- •If calculated creatinine clearance is < 45mL/min, a 24-hour urine collection for creatinine clearance may be performed
- •Subjects with documented Gilbert's disease may have bilirubin up to 2.5 mg/dL
- •Negative serum pregnancy test within 14 days prior to study treatment if a woman has child-bearing potential. Subjects of child bearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- •Ability to swallow and retain oral medications.
- •Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
- •Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the duration of study participation. Should a woman become pregnant while participating on study, she should inform the treating physician immediately.
排除标准
- •Gross residual tumor on imaging or positive margins after breast conserving surgery that are un-excised, as radiation dose in the study will be limited to 60 Gy.
- •Complete pathologic response to NAC.
- •Receipt of PARP inhibitor prior to RT.
- •Pregnant or expecting to conceive within the projected duration of the trial, starting with screening visit through 180 days after the last dose of trial treatment.
- •Prior history of radiation therapy to the ipsilateral breast and/or regional nodes is not allowed (prior RT to other sites is permitted).
- •Patients with breast augmentation implants are excluded.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to rucaparib.
- •Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. Bisphosphonates are permitted without restriction even during protocol treatment. Maintenance pembrolizumab is permitted during the protocol treatment.
- •Significant comorbidity: Patients with clinically significant and uncontrolled major disease or disorder that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit study compliance.
- •Ongoing therapy with other investigational agents. Patients may not be receiving any other investigational agents.
- •Unresolved toxicity from other agents. Patients with unresolved CTCAE v4.03 Grade 3 or greater toxicity from prior administration of another investigational drug and/or anti-cancer treatment are not eligible.
研究组 & 干预措施
Rucaparib Administered With Radiation
one dose level (200 mg BID, 200 mg QD, 300 mg BID, 300 mg QD or 400 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level.
Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.
干预措施: Rucaparib (Drug)
Rucaparib Administered With Radiation
one dose level (200 mg BID, 200 mg QD, 300 mg BID, 300 mg QD or 400 mg BID) concurrently with a 6-week course of radiotherapy and 4 additional weeks of maintenance rucaparib at the same dose level.
Radiotherapy will consist of 50 Gy in 2 Gy per fraction to the breast or chest wall with or without regional nodes plus a 10 Gy boost to the lumpectomy cavity, to a total dose of 60 Gy. A 10 Gy boost to the post-mastectomy scar is allowed at the discretion of the treating physician.
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Dose Limiting Toxicities
时间窗: 1 year
Number of Dose Limiting Toxicities encountered at each dose level. The trial will be monitored using TITE-CRM. Assuming a model for the time to occurrence of toxic response as a function of dose, the method allows information from all enrolled patients to be used when allocating a new patient to a dose level.
次要结局
未报告次要终点