A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients With Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- NRG Oncology
- 入组人数
- 450
- 试验地点
- 1,775
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This phase III trial studies how well letrozole with or without paclitaxel and carboplatin works in treating patients with stage II-IV low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. Letrozole is an enzyme inhibitor that lowers the amount of estrogen made by the body which in turn may stop the growth of tumor cells that need estrogen to grow. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving letrozole alone or in combination with paclitaxel and carboplatin works better in treating patients with low-grade serous carcinoma of the ovary, fallopian tube, or peritoneum compared to paclitaxel and carboplatin without letrozole.
详细描述
PRIMARY OBJECTIVE:
I. To examine if letrozole monotherapy/maintenance (L/L) is non-inferior to intravenous (IV) paclitaxel/carboplatin and maintenance letrozole (CT/L) with respect to progression-free survival (PFS) in women with stage II-IV primary low-grade serous carcinoma of the ovary or peritoneum after primary surgical cytoreduction.
SECONDARY OBJECTIVES:
I. To compare the nature, frequency and maximum degree of toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each treatment arm.
II. To compare the relative frequency of objective tumor response in those with measurable disease after cytoreductive surgery for each treatment arm.
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
- 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
- •Patients must have newly diagnosed, stage II-IV low-grade serous ovarian cancer (submission of pathology report[s] required). Ovarian cancer = ovarian, fallopian tube and primary peritoneal cancers
- •NOTE: Patients with a prior history of serous borderline tumors but a new diagnosis of stage II-IV low-grade serous ovarian cancer are eligible
- •p53 immunohistochemistry (IHC) is required and must show nonaberrant pattern (nonaberrant p53 expression is consistent with normal/wildtype TP53)
- •A copy of the pathology report that includes the diagnosis of low grade serous ovarian cancer and nonaberrant p53 IHC result must be submitted in RAVE. NOTE: If aberrant p53 expression is found on p53 IHC, the patient is NOT eligible (aberrant p53 expression is consistent with mutant TP53 and supports diagnosis of high grade serous ovarian cancer)
- •Appropriate stage for study entry based on the following diagnostic workup:
- •History/physical examination within 14 days prior to registration;
- •Radiographic tumor assessment within 28 days prior to registration. (23-MAY-2023)
- •Age >= 18
- •Patients must have undergone an attempt at maximal upfront cytoreductive surgery, with either optimal (=< 1 cm diameter residual disease/nodule) or suboptimal residual disease (> 1 cm diameter residual disease/nodule) status allowed
- •Patients must have undergone a bilateral salpingo-oophorectomy
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 14 days prior to registration
- •Patients must be within =< 8 weeks of primary cytoreductive surgery at time of randomization
- •Patients must be able to take per oral (P.O.) medications
- •Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl (within 14 days prior to registration)
- •Platelets greater than or equal to 100,000 cells/mcl (within 14 days prior to registration)
- •Creatinine less than or equal to 1.5 x upper limit of normal (ULN) (within 14 days prior to registration)
- •Bilirubin less than or equal to 1.5 x ULN (within 14 days prior to registration)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x ULN (within 14 days prior to registration)
- •The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
排除标准
- •Patients may not have received neoadjuvant or adjuvant chemotherapy or radiotherapy for the treatment of this disease
- •Patients may not have received previous hormonal therapy for the treatment of this disease
- •Patients with known hypersensitivity to letrozole or hypersensitivity/intolerance to carboplatin/paclitaxel therapy
- •Patients with severe cardiac disease:
- •Myocardial infarction or unstable angina within 6 months prior to registration
- •New York Heart Association (NYHA) class II or greater congestive heart failure
- •Patients with known central nervous system metastases
- •Patients with active (except for uncomplicated urinary tract infection) or uncontrolled systemic infection
- •Patients with >= grade 2 baseline neuropathy
- •Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
研究组 & 干预措施
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Biopsy Procedure (Procedure)
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Carboplatin (Drug)
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Imaging Procedure (Procedure)
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Letrozole (Drug)
Arm I (paclitaxel, carboplatin, letrozole)
Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole PO QD in the absence of disease progression or unacceptable toxicity. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Paclitaxel (Drug)
Arm II (letrozole)
Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Biopsy Procedure (Procedure)
Arm II (letrozole)
Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (letrozole)
Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Imaging Procedure (Procedure)
Arm II (letrozole)
Patients receive letrozole PO QD. Cycles repeat every 21 days for up to 6 cycles. Patients then receive letrozole orally PO QD in the absence of disease progression or unacceptable toxicity as maintenance therapy. Patients undergo blood collection and tumor biopsy during screening as well as medical imaging throughout the study.
干预措施: Letrozole (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Time from the randomized treatment assignment to documentation of disease progression (Response Evaluation Criteria in Solid Tumors 1.1) or death from any cause, whichever comes first, assessed up to 8 years
The PFS comparison will be assessed at the second interim and final analyses using a logrank test stratified by country and residual disease status. Estimates for the letrozole/letrozole (L/L) vs paclitaxel/carboplatin/letrozole (CT/L) hazard ratio and its confidence interval will be obtained using a stratified Cox proportional hazards model. Potential confounding factors, including the stratification factors, performance status and self-declared racial designation will be considered in a final exploratory model. A forest plot of treatment hazard ratios with confidence intervals within subgroups will also be reported. PFS will be characterized by treatment group with Kaplan-Meier plots and estimates of the median PFS.
次要结局
- Duration of response(Time from documentation of response under documentation of progression or death, which is observed first, assessed up to 8 years)
- Objective response rate (ORR)(Up to 8 years)
- Incidence of adverse events (AE)(Up to 8 years)
- Overall survival (OS)(Time between randomization and death from any cause, assessed up to 8 years)
- Adherence to letrozole maintenance therapy(At cycles 1, 6, and 12)