临床试验/NCT02657928

NCT02657928已完成2 期

A Phase 2 Trial of Ribociclib (LEE011) and Letrozole in ER Positive Relapsed Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinomas, and Endometrial Cancers.

Mayo Clinic3 个研究点分布在 1 个国家目标入组 40 人开始时间: 2016年7月8日最近更新: 2021年10月26日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Mayo Clinic
入组人数: 40
试验地点: 3
主要终点: Percentage of Patients Alive and Free of Progression at 12 Weeks (PFS12)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase II trial studies how well ribociclib and letrozole work in treating patients with estrogen receptor (ER) positive ovarian, fallopian tube, primary peritoneal, or endometrial cancer that has returned (come back) after a period of improvement. Ribociclib may stop the growth of tumor cells by blocking some enzymes needed for cell growth. Cancer cells that are estrogen receptor positive may need estrogen to grow. Letrozole lowers the amount of estrogen made by the body and this may stop the growth of tumor cells that need estrogen to grow. Giving ribociclib together with letrozole may be an effective treatment in patients with ovarian, fallopian tube, primary peritoneal, or endometrial cancer.

详细描述

PRIMARY OBJECTIVES:

I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher percentage of patients who are progression free at 12 weeks (PFS 12) as compared with that observed in prior studies with single agent letrozole.

SECONDARY OBJECTIVES:

I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher cancer antigen 125 (CA-125) response rate in patients with relapsed ER positive ovarian cancers and endometrial cancers as compared to that observed in previously reported single agent letrozole studies.

II. Median progression-free survival (PFS), overall survival (OS), the confirmed response rate, and adverse events.

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

•Ability to understand and the willingness to sign a written informed consent document
•Post-menopausal
•Histologically confirmed recurrent ovarian, fallopian tube or primary peritoneal carcinoma or endometrial cancer in post-menopausal women; NOTE: pure clear cell and pure mucinous carcinomas are ineligible; platinum sensitive, platinum resistant and platinum refractory disease are eligible; no limitations in the number of prior regimens
•Patient has disease amenable to biopsy and is agreeable to undergo a biopsy; NOTE: under unusual circumstances, submission of ascites material may be acceptable if a biopsy is not possible; this exception will require approval by one of the study principal investigators
•Willing to provide tissue samples for ER and retinoblastoma (RB) staining
•Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
•Tumors must stain positive for estrogen receptor (>= 10%) by immunohistochemistry (IHC)
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
•Absolute neutrophil count (ANC) >= 1000/mm^3
•Platelet count >= 100,000/mm^3
•Hemoglobin >= 9.0 g/dL
•Total bilirubin =< 1 x upper limit of normal (ULN); or total bilirubin =< 3.0 x ULN with direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert's syndrome
•Aspartate transaminase (aspartate aminotransferase [AST]) =< 2.5 x ULN (=< 5 x ULN in patients with liver metastasis)
•International normalized ratio (INR) =< 2
•Creatinine =< 1.5 mg/dL
•Potassium =< ULN (or corrected to =< ULN with supplements prior to registration)
•Total calcium (corrected for serum calcium) =< ULN (or corrected to =< ULN with supplements prior to registration)
•Magnesium =< ULN (or corrected to =< ULN with supplements prior to registration)
•Sodium =< ULN (or corrected to =< ULN with supplements prior to registration)
•Phosphorus =< ULN (or corrected to =< ULN with supplements prior to registration)
•Ability to swallow study medication
•Provide informed written consent
•Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
•Willing to provide tissue samples for correlative research purposes

排除标准

•Patients who have central nervous system (CNS) involvement unless they meet ALL of the following criteria:
•>= 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 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.)
•Clinically significant, uncontrolled heart disease or cardiac repolarization abnormalities and/or recent events 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 6 months prior to screening
•History of documented congestive heart failure (New York Heart Association functional classification III-IV)
•Documented cardiomyopathy
•Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
•Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third-degree AV block) long QT syndrome or family history of long QT syndrome
•Idiopathic sudden death or congenital long QT syndrome
•Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
•Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause torsades de pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
•Inability to determine the QT interval on screening (corrected QT interval [QTcF], using Fridericia's correction)
•Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
•Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse, at screening
•Tachycardia (heart rate > 110 at rest), by ECG or pulse at screening
•Inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF > 450 msec (using Fridericia's correction); NOTE: all as determined by screening ECG
•Patient is currently receiving any of the following medications and cannot be discontinued =< 7 days prior to starting study drug: known strong inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges or that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 or herbal preparations/medications or dietary supplements
•Patient is currently receiving or has received systemic corticosteroids within =< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment; NOTE: the following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)
•Patient has received radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom >= 30% of the bone marrow was irradiated
•Patient has had major surgery =< 14 days prior to registration or has not recovered from major side effects (tumor biopsy is not considered as major surgery)
•Known to be human immunodeficiency virus (HIV) positive (testing not mandatory)
•Patient has a known hypersensitivity to any of the excipients of ribociclib
•Patient is currently receiving warfarin or other Coumarin-derived anticoagulant for treatment, prophylaxis or otherwise; NOTE: therapy with apixaban, dabigatran, heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed
•Participation in a prior investigational study within 30 days prior to enrollment or =< 5 half-lives of the investigational product, whichever is longer
•Patient has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade < 3 (exception to this criterion: patients with any grade of alopecia or neuropathy are allowed to enter the study)
•Patient with a Child-Pugh score B or C
•Patient 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 significant small bowel resection)
•Prior therapy with ribociclib or an aromatase inhibitor (letrozole, anastrozole or exemestane)
•Patient has received systemic chemotherapy =< 3 weeks prior to registration

研究组 & 干预措施

Treatment (ribociclib and letrozole)

Experimental

Patients receive ribociclib PO daily and letrozole PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

干预措施: Laboratory Biomarker Analysis (Other)

Treatment (ribociclib and letrozole)

Experimental

Patients receive ribociclib PO daily and letrozole PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

干预措施: Letrozole (Drug)

Treatment (ribociclib and letrozole)

Experimental

Patients receive ribociclib PO daily and letrozole PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

干预措施: Ribociclib (Drug)

结局指标

主要结局

Percentage of Patients Alive and Free of Progression at 12 Weeks (PFS12)

时间窗: At 12 weeks

The percentage of patients who are progression-free at 12 weeks (PFS12) is defined as patients who are alive and progression free at 12 weeks. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

次要结局

Progression-free Survival(From registration to the first of either disease progression or death from any cause, assessed up to 2 years)
The Number of Patients With CA-125 Response(Up to 2 years)
Overall Survival(From registration to death from any cause, assessed up to 2 years)
The Number of Patients With Confirmed Response (Complete Response or Partial Response)(Up to 2 years)
The Number of Treatment-related Grade 3 or Higher Adverse Events(Up to 30 days post-treatment)

研究者

发起方

Mayo Clinic

申办方类型

Other

责任方

Sponsor

研究点 (3)

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