A Randomized, Multicenter, Double-blind, Phase 3 Study of Amcenestrant (SAR439859) Versus Tamoxifen for the Treatment of Patients With Hormone Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative or Positive, Stage IIB-III Breast Cancer Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Invasive Breast Cancer-free Survival (IBCFS)
研究概览
简要总结
This was a phase III, randomized, double blind, multicenter, 2-arm study evaluating the efficacy and safety of amcenestrant compared with tamoxifen in participants with hormone receptor-positive early breast cancer who discontinued adjuvant aromatase inhibitor (AI) therapy due to treatment related toxicity. The primary objective was to demonstrate the superiority of amcenestrant versus tamoxifen on invasive breast cancer-free survival.
The treatment duration per participant was to be 5 years, followed with a subsequent 5-years follow-up period. For the treatment period, visits were scheduled at the start of treatment, then at 4 weeks and 12 weeks after treatment start, and then every 12 weeks for the first 2 years and every 24 weeks for year 3 to 5. For the follow-up period, visits were scheduled 30 days after last treatment and then every 12 months. Three periods were planned:
- A screening period of up to 28 days,
- A treatment period of up to 5 years,
- A follow-up period of up to 5 years.
详细描述
Study duration per participant was to be approximately 10 years.
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)
盲法说明
Double-dummy
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult participants with histologically confirmed diagnosis of adenocarcinoma of the breast with documentation of hormone receptor-positive status, irrespective of human epidermal growth factor receptor 2 (HER2) status NOTE: Participants with HER2-positive breast cancer were eligible only if they had completed their adjuvant anti-HER2 treatment and chemotherapy.
- •With Stage IIB or Stage III (invasive breast cancer) who had undergone breast surgery and adjuvant radiation (if indicated) for the current malignancy.
- •Who had received prior aromatase inhibitors (AIs) (letrozole, anastrozole or exemestane or any sequence thereof) per the following:
- •Adjuvant AI therapy was discontinued due to AI treatment-related toxicity; Minimum of 6 months duration and maximum of 30 months duration (from initiation of first AI if there was a switch between AIs) of AI therapy was required.
- •Absence of locoregional and/or advanced/metastatic disease
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
- •Capable of giving signed informed consent.
排除标准
- •Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant and/or tamoxifen. Participants unable to swallow normally or unable to take tablets and capsules. Predictable poor compliance to oral treatment. Active inflammatory bowel disease or chronic diarrhea, active hepatitis A/B/C, hepatic cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection or banding procedures.
- •History of prior breast cancer treated with AI.
- •Any other solid tumor or lymphoma diagnosis was not allowed except if the participant had been free from disease for equal to greater than (=>5) years.
- •Pregnant or nursing women, or women of child-bearing potential without a negative pregnancy test prior to randomization.
- •Participants with unrecovered acute toxic effects of prior AI therapy or surgical procedures.
- •Uncontrolled intercurrent illness, including psychiatric conditions that would have limited compliance with study requirements.
- •Treatment with any selective estrogen receptor degrader (SERD), tamoxifen or toremifene were not allowed as prior adjuvant therapy but could have been used as neoadjuvant therapy for a total duration of 3 months. Participants who were treated with a SERD, tamoxifen or toremifene in the neoadjuvant setting and who experienced disease progression were not allowed. Prior treatment with raloxifene or tamoxifen for bone health, risk reduction, or a prior breast cancer was allowed provided this was discontinued at least 3 years before diagnosis of current breast cancer.
- •Ongoing treatment with HER2 directed therapy. Appropriate wash out between the last dose of HER2 directed therapy and randomization should have been at least 4 weeks.
- •The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Amcenestrant with tamoxifen-matching placebo arm
Amcenestrant dose, once daily, continuously. Tamoxifen-matching placebo, once daily, continuously.
干预措施: Amcenestrant (Drug)
Amcenestrant with tamoxifen-matching placebo arm
Amcenestrant dose, once daily, continuously. Tamoxifen-matching placebo, once daily, continuously.
干预措施: Tamoxifen-matching placebo (Drug)
Tamoxifen with amcenestrant-matching placebo
Tamoxifen dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously.
干预措施: Tamoxifen (Drug)
Tamoxifen with amcenestrant-matching placebo
Tamoxifen dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously.
干预措施: Amcenestrant-matching placebo (Drug)
结局指标
主要结局
Invasive Breast Cancer-free Survival (IBCFS)
时间窗: From randomization to the date of first occurrence of IBCFS event (maximum exposure duration: 155 days)
IBCFS was defined according to standardized definitions for efficacy outcome measure in adjuvant breast cancer trials (STEEP) criteria version 2.0 as the time interval from the date of randomization to the date of the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence (IIBTR): invasive breast cancer involving the same breast parenchyma as the original primary; local-regional invasive breast cancer recurrence: invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast; distant recurrence: metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer, invasive contralateral breast cancer; death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause.
次要结局
- Change From Baseline in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30): Global Health Status/Quality of Life (GHQ) Scale Score(Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 34, 40, 46, 52, & 58 and at end of treatment (maximum exposure: any day up to 155 days))
- Plasma Concentration of Amcenestrant(Pre-dose on Cycle 2 Day 1, Cycle 7 Day 1, Cycle 13 Day 1 and Cycle 25 Day 1)
- Invasive Disease-Free Survival (IDFS)(From randomization to the date of first occurrence of IDFS event (maximum exposure duration: 155 days))
- Distant Recurrence-free Survival (DRFS)(From randomization to the date of the first occurrence of distant recurrence or death due to any cause, whichever occurs first (maximum exposure duration: 155 days))
- Locoregional Recurrences-free Survival (LRRFS)(From randomization to the date of the first occurrence of local/regional ipsilateral recurrence or breast cancer or death due to any cause, whichever occurs first (maximum exposure duration: 155 days))
- Overall Survival (OS)(From randomization to the date of death due to any cause (maximum exposure duration: 155 days))
- Breast Cancer-specific Survival (BCSS)(From randomization to the date of death due to breast cancer (maximum exposure duration: 155 days))
- Change From Baseline in Overall Side Effect Bother As Measured By Functional Assessment of Cancer Therapy Item GP-5 (FACT-GP5) Scale Scores(Baseline, Cycle 3, 4, 5, 6, 7, 10, 13, 16, 19, 22, 25, 28, 34, 40, 46, 52, & 58 and at end of treatment (maximum exposure: any day up to 155 days))
- Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Breast Cancer Specific Module (EORTC-QLQ-BR23): Systemic Therapy Side Effects Scale Score(Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 34, 40, 46, 52, & 58 and at end of treatment (maximum exposure: any day up to 155 days))