EXemestane in Progesterone and/or Estrogen Receptor Positive Epithelial Ovarian Cancer: A Randomized Phase III Trial, EXPERT
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 47
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
In this Italian, multicenter, randomized, double-blind, placebo controlled, phase III study the efficacy of exemestane will be evaluated in addition to the standard front line treatment in patients with hormone-receptor-positive high grade serous or endometrioid Epithelian Ovarian Cancer (EOC). The patients enrolled in the EXPERT trial will receive exemestane or placebo in addition to standard treatment. Patients and investigators will be blinded to study treatment.
The hypothesis underlying the proposed clinical trial is that exemestane added to standard first line therapy will significantly prolong median progression free survival (PFS).
详细描述
Estrogen and Progesterone play a role in promoting EOC growth, metastasis, and progression. Recent data show that ER and PgR expression is frequent in high grade EOC and has prognostic significance. A large meta-analysis showed a clinical benefit with any endocrine treatment, and in particular for aromatase inhibitors (AIs), with a greatere benefit for ER+ and/or PgR+ patients and platinum sensitive tumors. Moreover, the analysis of a few randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy in EOC, suggesting that ER and PgR have a predictive role and that inhibition of their activation could therefore be a treatment option for EOC.
Exemestane is a well-tolerated and effective AI in endocrine sensitive breast cancer which inhibits the production of Estrogens by the adipose tissue in postmenopausal women.
In this Italian, multicentre, randomized, double-blind, placebo controlled, phase III study will be assessed the efficacy of exemestane versus placebo in addition to the standard front line treatment in patients with high grade serous or endometrioid EOC, IHC positive (≥ 10%) ER or PgR disease, stage IIB - IV according to the FIGO classification.
The primary objective of the study is to test the superiority of exemestane over placebo in addition to the standard front line treatment in terms of PFS.
Secondary Objectives are:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years
- •Citologically or histologically confirmed high grade serous or endometrial epithelial ovarian cancer, including cancer of fallopian tube and peritoneum. For patients who are candidates for neoadjuvant chemotherapy, diagnosis must be documented via imaging or a core tissue (not fine needle aspiration) biopsy.
- •Disease stage IIB to IV according to FIGO classification. For patients who are candidates for neoadjuvant chemotherapy, stage IIB-IV should be documented via imaging or a core tissue (not fine needle aspiration) biopsy.
- •Patients must have completed a surgical debulking procedure, or be candidates for neoadjuvant chemotherapy. For patients enrolling after debulking surgery, randomization should occur at a maximum of 12 weeks and not before 4 weeks after surgery.
- •Immunoistochemically determined positivity (≥ 10%) for Progesterone and/or Estrogen receptor expression, including determination on cytology smears from ascitic fluid if surgery is differed.
- •Measurable or evaluable disease confirmed by radiological imaging, or histological proven ovarian cancer in the absence of postoperatively measurable or evaluable lesions
- •Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-
- •Written, informed consent obtained prior to any study-specific procedures.
排除标准
- •Previous systemic therapy for ovarian cancer.
- •Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer.
- •Inadequate bone marrow, hepatic or renal functions, assessed within 7 days prior to randomization.
- •Treatment with hormonal contraceptives during the previous 3 months from diagnosis.
- •Concurrent comorbidities, which contraindicates the administration of chemotherapy, or endocrine therapy.
- •Pregnant or lactating patients.
- •Inability or unwillingness to swallow tablets.
研究组 & 干预措施
Exemestane
Standard chemotherapy: paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.
Exemestane: single oral tablet of 25 mg/day until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.
干预措施: Exemestane (Drug)
Placebo
Standard chemotherapy : paclitaxel 175 mg/m2 + carboplatin AUC 5, on day 1 every 21 days ± bevacizumab 15mg/kg, on day 1 every 21 days. Chemotherapy will be administered for 6 cycles; Bevacizumab will be administered as up to a maximum of 22 cycles. Patients unfit for standard treatment can receive a weekly schedule of treatment or monotherapy with carboplatin alone. Neoadjuvant chemotherapy is allowed in patients unfit for primary elective surgery.
Placebo: single oral tablet until disease progression, unacceptable toxicity or physician/patient decision to withdraw, whichever comes first.
干预措施: Placebo oral tablet (Other)
结局指标
主要结局
Progression free survival (PFS)
时间窗: Up to 20 months
PFS id defined for each patient as the time from the date of randomization to the date of local or regional relapse, distant metastasis, second primary malignancy or death from any cause, whichever comes first. Patients not recurred, progressed or died while on study or lost to follow-up will be censored at their last disease assessment date.
次要结局
- Quality of Life: Menopause Quality of Life (MENQoL) questionnaire(Up to 20 months)
- Compliance - Reasons for discontinuation and treatment modification(Up to 20 months)
- Compliance - Dose intensity(Up to 20 months)
- Safety (Adverse Events)(Up to 20 months)
- Overall survival (OS)(Up to 20 months)
- Objective Response Rate (ORR)(a CT-scan will be performed every 4 months. Up to 20 months from last patients randomized)
- Compliance - Number of administered cycles(Up to 20 months)
研究者
Andrea DeCensi
Principal Investigator
Ente Ospedaliero Ospedali Galliera