A Phase 2 Trial of Letrozole and Everolimus in Relapsed Hormone Receptor Positive Ovarian, Fallopian Tube or Primary Peritoneal Carcinomas
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Percentage of Patients Alive and Progression Free Survival at 12 Weeks
研究概览
简要总结
This pilot, phase II trial studies how well everolimus and letrozole work in treating patients with hormone receptor positive ovarian, fallopian tube, or primary peritoneal cavity cancer that has come back. Everolimus and letrozole may stop the growth of tumor cells by blocking some the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. Demonstrate that the combination of letrozole and everolimus leads to a higher percentage of patients who are free of progression at 12 weeks (PFS 12) as compared with that observed in a previously reported phase 2 trial of letrozole alone for relapsed ovarian carcinomas.
SECONDARY OBJECTIVES:
I. Cancer antigen (CA)-125 response, progression-free survival (PFS), overall survival (OS), the confirmed response rate, and adverse events.
TERTIARY OBJECTIVES:
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
- •Histologically confirmed estrogen receptor positive (greater than 10%) recurrent ovarian, fallopian tube or primary peritoneal carcinoma in post-menopausal women; note: pure clear cell and pure mucinous carcinomas are ineligible; both 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 will require approval by one of the study principal investigators
- •Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelet count >= 100,000/mm^3
- •Hemoglobin > 9.0 g/dL
- •Total serum bilirubin =< 2 mg/dL
- •Aspartate transaminase (AST) =< 2.5 x upper limit of normal (ULN) (=< 5 x ULN in patients with liver metastasis)
- •International normalized ratio (INR) =< 2
- •Creatinine =< 1.5 x ULN
- •Fasting serum cholesterol =< 300 mg/dL or =< 7.75 mmol/L and fasting triglycerides =< 2.5 x ULN; in case of any of these thresholds be exceeded, the patient can only be included after initiation of appropriate lipid lowering medications
- •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
- •Any of the following
- •Pregnant women
- •Nursing women
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including but not limited to any of the following that would limit compliance with study requirements:
- •Ongoing or active severe infection
- •Liver disease such as cirrhosis
- •Decompensated liver disease
- •Symptomatic congestive heart failure (New York heart Association class III or IV)
- •Unstable angina pectoris, serious uncontrolled cardiac arrhythmia, myocardial infarction =< 6 months prior to registration
- •Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide [DLCO] 50% or less of normal and oxygen [O2] saturation 88% or less at rest on room air)
- •Active bleeding diathesis
- •Psychiatric illness
- •Known to be human immunodeficiency virus (HIV) positive
- •Receiving any other investigational agent =< 4 weeks prior to registration which would be considered as treatment for the primary neoplasm
- •Other active malignancy =< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix, uterus or breast; note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer
- •Patients currently receiving anticancer therapies or who have received anticancer therapies =< 4 weeks prior to registration (including chemotherapy, radiation therapy, antibody based therapy, etc.)
- •Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
- •Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
- •Uncontrolled diabetes mellitus as defined by hemoglobin (Hb)A1c > 8% despite adequate therapy; note: patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
- •Chronic treatment with corticosteroids or other immunosuppressive agents; note: topical or inhaled corticosteroids are allowed
- •Patients who have received live attenuated vaccines =< 1 week prior to registration and during the study; note: patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
- •History of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
- •Prior therapy with everolimus or an aromatase inhibitor
- •Known brain metastasis
- •Active and chronic viral hepatitis (i.e. quantifiable serum hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen [HBsAg], or quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA] in serum)
研究组 & 干预措施
Treatment (everolimus and letrozole)
Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Everolimus (Drug)
Treatment (everolimus and letrozole)
Patients receive everolimus PO QD and letrozole PO QD 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 (everolimus and letrozole)
Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Letrozole (Drug)
结局指标
主要结局
Percentage of Patients Alive and Progression Free Survival at 12 Weeks
时间窗: 12 weeks
The percentage of PFS12 successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following: * Any new disease and/or clear progression of evaluable disease; OR * 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.
次要结局
- Number of Participants Experiencing Adverse Events(Up to 30 days post-treatment)
- Overall Suravival(OS)(Time from registration to death from any cause, assessed up to 2 years)
- Percentage of Participants With CA-125 Response(Up to 2 years)
- Progression Free Survival (PFS)(Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years)
- Confirmed Response Rate, Estimated Using RECIST 1.1 Criteria(Up to 24 weeks)