ENGOT-EN3-NSGO/PALEO: A Randomized, Double-blind, Placebo-controlled, Phase II Trial of Palbociclib in Combination With Letrozole Versus Placebo in Combination With Letrozole for Patients With Estrogen Receptor Positive Advanced or Recurrent Endometrial Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm
研究概览
简要总结
This randomized double-blind, placebo-controlled phase 2 trial is evaluating superiority of Letrozole-palbociclib combination versus letrozole-placebo combination in ER positive endometrioid adenocarcinoma of endometrium
详细描述
This multicenter, prospective, randomized, double-blind, placebo-controlled phase 2 study is evaluating the efficacy of letrozole-palbociclib combination against letrozole-placebo combination in women with ER+ advanced or relapsed endometrial cancer.
Stratification
Patients are stratified according to:
- Number of prior lines of therapy (primary advanced disease vs. 1st relapse vs. ≥2 relapses)
- Measurable vs. evaluable disease
- Prior use of MPA/Megace
Randomization 1:1 randomization The patients with prior MPA/Megace treatment will be capped to a maximum of 50%.
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
- Double (Participant, Investigator)
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
- •Histological confirmed endometrial cancer of endometrioid type. Mixed tumor histology is allowed if the non-endometrioid component is less than 5%. Tumor must be estrogen receptor positive.
- •Patients may have received adjuvant chemotherapy for stage 1 or
- •Patients may have received any lines of chemotherapy for primary advanced (stage 3-4) or relapsed disease.
- •Patients may have received external beam radiotherapy, brachytherapy, and surgery.
- •Patient may have received maximum one line of endocrine therapy containing MPA/Megace only.
- •Patients must have measureable disease or evaluable disease on CT scan according to RECIST 1.1 outside irradiated field.
- •Patients must give informed consent
- •Patients must have a WHO performance status of 0-1
- •Patients must have an adequate bone-marrow, renal and hepatic function
- •Life expectancy of at least 12 weeks
- •Patients must be fit to receive combination therapy
- •Patient's age >18 years
- •Patient is post-menopausal. Patients under the age of 55 with intact ovaries shall undergo hormonal verification.
- •Patients with preserved reproductive capacity must have a negative pregnancy test (β-HCG test in urine or serum) prior to commencing study treatment
排除标准
- •Non-endometrioid adenocarcinomas, sarcomas, small cell carcinoma with neuroendocrine differentiation or non-epithelial cancers.
- •Previous anti-cancer endocrine therapy other than MPA/Megace. This means that eg. tamoxifen is not allowed prior to study entry.
- •Concurrent cancer therapy
- •Previous treatment with Palbociclib or other CDK inhibitors.
- •Concurrent treatment with an investigational anticancer agent or participation in another anticancer clinical trial within 21 days before entering into study.
- •Treatment within 21 days prior to randomization with any investigational drug, radiotherapy,
- •Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period.
- •Previous malignant disease, except patients with other malignant disease, for which the patient has been disease-free for at least three years. Concurrent other malignant disease except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin.
- •Active infection or other serious underlying medical condition, which might prevent the patient from receiving treatment or to be followed.
- •Evidence of significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator's judgment, makes the patient inappropriate for this study.
- •Known uncontrolled hypersensitivity to the investigational drugs.
- •History of major thromboembolic event defined as:
- •History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months.
- •History of clinically significant hemorrhage in the past 3 months.
- •Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization).
- •Significant cardiovascular diseases, including uncontrolled hypertension, uncontrolled clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA III, severe peripheral vascular disease, clinically significant pericardial effusion.
- •Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.
- •Active or chronic hepatitis C and/or B infection
- •Persistence of clinically relevant grade 3-4 therapy related toxicity from previous chemo and/or radiotherapy
- •Known hypersensitivity to the trial drugs, or to their excipients.
- •Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
- •Unable or unwilling to swallow tablets/capsules
研究组 & 干预措施
Letrozole + placebo
letrozole 2.5mg once daily days 1-28 every 28 days shall be administered until progression of disease or unacceptable toxicity. Letrozole is administered as standard of care in both study arms.
Placebo for palbociclib once daily days 1-21 every 28 days shall be administered until progression of disease or unacceptable toxicity.
干预措施: Letrozole (Drug)
Letrozole + palbociclib
Palbociclib 125mg once daily days 1-21 every 28 days shall be administered until progression of disease or unacceptable toxicity.
letrozole 2.5mg once daily days 1-28 every 28 days shall be administered until progression of disease or unacceptable toxicity.
Letrozole is administered as standard of care in both study arms.
干预措施: Palbociclib/placebo (Drug)
Letrozole + palbociclib
Palbociclib 125mg once daily days 1-21 every 28 days shall be administered until progression of disease or unacceptable toxicity.
letrozole 2.5mg once daily days 1-28 every 28 days shall be administered until progression of disease or unacceptable toxicity.
Letrozole is administered as standard of care in both study arms.
干预措施: Letrozole (Drug)
结局指标
主要结局
Progression-Free Survival (PFS). Increase in median PFS in experimental arm versus comparator arm
时间窗: 26 months
To be measured (in months) and reported
次要结局
- Time to Second Subsequent Therapy (TSST)(48 months)
- Progression-Free Survival 2 (PFS2)(48 months)
- Compliance in the two treatment arms.(48 months)
- Dose reductions/interruptions in the two treatment arms(48 months)
- PFS of patients in the sub-populations as described under stratification factors. Increase in median PFS in experimental arm versus comparator arm(26 months)
- Overall Response Rate (ORR) according to RECIST(26 months)
- Disease Control Rate (DCR) for at least 12 weeks(26 months)
- Time to First Subsequent Therapy (TFST)(36 months)
- Patient Reported Outcomes (PROs) like Quality of Life questionnaire EORTC-QLQ-C30 & EORTC-QLQ-EN24(48 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(48 months)