NCT02599363已完成1 期
A Phase I Trial of Ribocilcib (LEE011) and Weekly Paclitaxel in Patients With Rb+ Advanced Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
This is a Phase I study to assess the safety and Maximum tolerated dose (MTD) of paclitaxel + ribociclib (LEE011) in patients with Rb+, advanced breast cancer. Dose escalation will be performed using standard 3 + 3 dosing strategy. The starting dose of ribociclib (LEE011) is 200 mg once daily; dose escalation proceeds in 200 mg increments up to a maximum of 600 mg. Dose-limiting toxicities (DLT) will be based upon first-cycle toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Patient must have histologically or cytologically confirmed breast cancer that is now metastatic; any ER, PR or HER2 status is allowed.
- •Biopsy confirming metastatic breast cancer and Retinoblastoma protein (Rb) positivity by immunohistochemistry prior to enrolling on this protocol is required.
- •Biopsy must be obtained immediately before study enrollment; no intervening treatments are allowed.
- •Patient must have measurable disease defined by RECIST 1.1 criteria.
- •Age ≥18 years
- •Patient must have received ≤3 prior cytotoxic regimens in the metastatic setting.
- •Performance status of 0-1 on the ECOG Performance Scale.
- •The subject must have adequate organ function, defined as follows
- •Serum creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
- •In the absence of liver metastases, alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 2.5 x ULN. If the patient has liver metastases, ALT and AST < 5 x ULN.
- •Total bilirubin < ULN; or total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN in patients with well documented Gilbert's Syndrome.
- •For subjects without extensive bone metastases: alkaline phosphatase levels < 2.5 x ULN
- •Potassium, total calcium (corrected for serum albumin), magnesium, sodium and phosphorus within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication
- •INR ≤ 1.5 unless on warfarin in which case INR <3.0 is acceptable.
- •The subject must have adequate marrow function, defined as follows
- •Leukocytes Absolute neutrophil count (ANC) ≥1500/mm3
- •Platelets ≥100,000/mm3, and
- •Hemoglobin ≥9 g/dL
- •The subject must be able to swallow ribociclib (LEE011)
- •Exclusion Criteria
- •Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of Study Day 1 or within 5 half-lives of the investigational product, whichever is longer, with the exception of a prior CDK 4/6 inhibitor.
- •Patient has had prior toxicity from a CDK 4/6 inhibitor necessitating discontinuation of the drug. Patient may have had prior treatment with a cdk 4/6 inhibitor in the adjuvant or metastatic setting.
- •Patient who has had chemotherapy or exposure to a CDK 4/6 inhibitor within 3 weeks (6 weeks for nitrosoureas, mitomycin C or bevacizumab) who has not recovered from the adverse events due to previous agents administered more than 4 weeks prior to Study Day
- •Hormonal therapy must be discontinued at least 24 hours prior to starting study treatment.
- •Patient is unable to have a biopsy of a metastatic site for Rb testing, because the biopsy is felt to be too invasive or risky by the treating physician.
- •Patient has not received available therapies that confer clinical benefit.
- •Patient has known active CNS metastases and/or carcinomatous meningitis. However, patients with CNS metastases (including brain metastases) are eligible for the study provided they are clinically stable and have met ALL of the following criteria:
- •At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
- •Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.
- •Patient has known hypersensitivity to any of the excipients of ribociclib
- •The subject has uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection
- •Diabetes mellitus
- •Symptomatic congestive heart failure (see 5.2.14), unstable angina pectoris, stroke or myocardial infarction within 12 months of screening
- •Patient has baseline neuropathy of ≥ grade
- •Patients who have known allergic reactions to paclitaxel or IV contrast dye despite standard prophylaxis.
- •The subject is known to be positive for the human immunodeficiency virus (HIV). Note: baseline HIV screening is not required
- •The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee.
- •Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- •Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- •Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).
- •Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- •History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 12 months prior to screening
- •History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- •Documented cardiomyopathy
- •Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
- •History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT Syndrome or conduction abnormality within 12 months of screening
- •Congenital long QT syndrome or family history of long QT syndrome
- •Bradycardia (heart rate <50 at rest), by ECG or pulse, at screening
- •Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
- 另有 20 项未显示
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation Treatment Arm
Experimental
干预措施: Ribociclib (LEE011) (Drug)
Dose Escalation Treatment Arm
Experimental
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Number of Adverse Events
时间窗: 3 years
次要结局
未报告次要终点
研究者
研究点 (1)
Loading locations...
相似试验
进行中（未招募）
1 期
Ribociclib, Tucatinib, and Trastuzumab for the Treatment of HER2 Positive Breast CancerAnatomic Stage II Breast Cancer AJCC v8Anatomic Stage IIA Breast Cancer AJCC v8Anatomic Stage IIB Breast Cancer AJCC v8Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIB Breast Cancer AJCC v8Anatomic Stage IIIC Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Invasive Breast CarcinomaLocally Advanced HER2-Positive Breast CarcinomaMetastatic HER2-Positive Breast CarcinomaPrognostic Stage IB Breast Cancer AJCC v8Prognostic Stage II Breast Cancer AJCC v8Prognostic Stage IIA Breast Cancer AJCC v8Prognostic Stage IIB Breast Cancer AJCC v8Prognostic Stage III Breast Cancer AJCC v8Prognostic Stage IIIA Breast Cancer AJCC v8Prognostic Stage IIIB Breast Cancer AJCC v8Prognostic Stage IIIC Breast Cancer AJCC v8Prognostic Stage IV Breast Cancer AJCC v8NCT05319873Jonsson Comprehensive Cancer Center18
已完成
1 期
Paclitaxel, Cisplatin, and Veliparib in Treating Patients With Advanced, Persistent, or Recurrent Cervical CancerCervical AdenocarcinomaCervical Adenosquamous CarcinomaCervical Squamous Cell Carcinoma, Not Otherwise SpecifiedRecurrent Cervical CarcinomaStage IVB Cervical Cancer AJCC v6 and v7NCT01281852National Cancer Institute (NCI)37
已完成
1 期
Phase I and Pharmacokinetic Trial of Paclitaxel (Taxol) Given as a 3-Hour Infusion in Pediatric Patients With Refractory MalignancyNeoplasmsNCT00001387National Cancer Institute (NCI)25
招募中
1 期
Study of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, HR+/HER2- Breast CancerBreast CancerNCT05996107University of Michigan Rogel Cancer Center30
已完成
1 期
A Trial of Weekly Paclitaxel With Oncothermia and Weekly cisPlatin With Oncothermia in Patients With Recurrent or Persistent Ovarian CancerEpithelial Ovarian CarcinomaFallopian Tube CarcinomaPrimary Peritoneal CarcinomaNCT02344095Seoul National University Hospital12