TBCRC 042 - A Randomized Phase II Window-of-Opportunity Trial of Ruxolitinib in Patients With High Risk and Premalignant Breast Conditions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 84
- 试验地点
- 11
- 主要终点
- Change in Apoptosis
研究概览
简要总结
This study is evaluating how ruxolitinib affects premalignant breast cells. One half of the study participants will receive ruxolitinib for approximately 15 days, and the other half will receive a placebo (sugar pill) for approximately 15 days. Once study participants have completed their ruxolitinib or placebo, participants will undergo surgery to remove the premalignant breast tissue.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a breast biopsy showing ADH (atypical ductal hyperplasia), ALH (atypical lobular hyperplasia), LCIS (lobular carcinoma in situ), or DCIS (ductal carcinoma in situ) requiring surgical excision. Microinvasive disease is allowed.
- •NOTE: Tissue from the diagnostic biopsy must be accessible/available for research correlates (i.e., a tissue block or ~10 unstained slides). Due to the nature of the study, fewer slides may be accepted with prior permission from the Protocol Chair if there is insufficient tissue.
- •Women and men age 18 and older.
- •Adequate hematologic and organ function, defined as follows:
- •Absolute neutrophil count ≥ 1500/mm3
- •Hemoglobin ≥ 9.0 g/dL
- •Platelet levels >200 x 109/L
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
- •AST/ALT ≤ 2.5 x institutional ULN
- •Alkaline phosphatase ≤ 5 x institutional ULN
- •Creatinine clearance > 50 mL/min as calculated by the Cockcroft-Gault method
- •Willing to not use concomitant strong CYP3A4 inhibitors as this could interfere with the metabolism of ruxolitinib (i.e azole antifungals, clarithromycin, conivaptan, grapefruit juice, mibefradil, nefazodone, protease inhibitors, telithromycin).
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
- •If the patient undergoes germline genetic testing, the results must be received prior to randomization, as the results may affect the surgical approach and, in turn, the date of surgical excision.
- •Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign a written informed consent document.
排除标准
- •Treatment with selective estrogen receptor modulators (SERMs) or aromatase inhibitors for breast cancer prevention within 1 year prior to starting study treatment.
- •Treatment with any other investigational agents within 30 days of starting study treatment.
- •Current diagnosis of invasive breast cancer (current microinvasive disease is allowed), or previous history of invasive breast cancer diagnosed within the last 5 years.
- •NOTE: If previous history of ER+ invasive breast cancer diagnosed > 5 years ago, patient must be off endocrine therapy for at least 1 year prior to starting study treatment.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, end stage renal disease (ESRD), or psychiatric illness/social situations that would limit compliance with study requirements.
- •Women who are pregnant or nursing.
- •HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib.
- •Prior or current treatment with a JAK inhibitor, for any indication.
- •Known active Hepatitis B or C.
研究组 & 干预措施
Placebo
Participants will receive a placebo (sugar pill) that is designed to mimic ruxolitinib. The placebo will be supplied as four, 5 mg tablets. Participants assigned to this arm will take four, 5 mg tablets by mouth twice daily for 15 days (+/- 5 days).
干预措施: Placebo (for Ruxolitinib) (Drug)
Ruxolitinib
Participants will receive ruxolitinib 20 mg by mouth twice daily for 15 days (+/- 5 days). Ruxolitinib will be supplied as four, 5 mg tablets.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Change in Apoptosis
时间窗: 15 days (+/- 5 days)
The number of premalignant breast cells in apoptosis at the time of diagnosis will be compared to the number of cells in apoptosis following treatment with 15 (+/- 5) days of ruxolitinib or placebo.
次要结局
- pSTAT5(15 days (+/- 5 days))
- Proliferation/Apoptosis Biomarkers(15 days (+/- 5 days))
研究者
Julie Nangia
Assistant Professor
Baylor Breast Care Center