Randomized Phase II Study of Fulvestrant With or Without Ganetespib in Patients With Hormone Receptor-Positive, Metastatic Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 5
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Ganetespib is a drug that may stop cancer cells from growing. This drug has been used in other research studies and laboratory experiments. It has also been studied in phase I trials, where the appropriate dosing has been determined. Ganetespib is considered an "HSP90 inhibitor". By blocking HSP90, ganetespib is thought to reduce the ability of cancer cells to become resistant to treatment.
Fulvestrant is a hormonal therapy that works by attaching to estrogen receptors. In doing so, it can block the effect of estrogen on cancer cells. In addition, fulvestrant causes a decrease in the number of estrogen receptors. Fulvestrant is a drug that is approved by the FDA for treatment of metastatic, hormone receptor positive breast cancer, based upon the results of phase III clinical trials.
In the laboratory, adding ganetespib to fulvestrant appears to improve its effectiveness. It is not known whether this is true in humans. In this research study, we are evaluating the effect of the addition of ganetespib to fulvestrant in participants with hormone receptor-positive, metastatic breast cancer.
详细描述
Because no one knows which of the study options is best, you will be "randomized" into one of the study groups: Arm A: Fulvestrant or Arm B: Fulvestrant plus Ganetespib. You will have a one-third chance of being placed in Arm A and a two-thirds chance of being placed in Arm B.
If you are initially placed in Arm A but your disease progresses, you will have the option of receiving the combination of fulvestrant plus ganetespib as part of Arm C.
You will undergo the following procedures during the research study: study drug(s), blood tests, clinical exams and scans/imaging tests.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed invasive breast cancer that is metastatic or unresectable locally advanced
- •Estrogen and/or progesterone receptor positive breast cancer
- •HER2 negative
- •Measurable disease is required (effective 4/30/14: all non-measurable [evaluable] disease slots have been filled)
- •Endocrine resistant breast cancer
- •May have received up to one prior line of chemotherapy for metastatic or unresectable locally advanced breast cancer
- •May have initiated bisphosphonate therapy prior to start of protocol therapy
- •Must be at least 2 weeks from prior chemotherapy or radiotherapy
- •ECOG performance status of 0 or 1
- •Availability of tissue block from initial breast cancer diagnosis and/or metastatic recurrence
- •For subjects with biopsy-accessible disease, must be willing to undergo a required on-treatment research biopsy
- •Adequate IV access
排除标准
- •Pregnant or breastfeeding
- •Prior treatment with HSP90 inhibitor
- •Prior treatment with fulvestrant
- •Concurrent treatment with commercial agents or other agents with the intent to treat the participant's malignancy
- •Untreated or progressive brain metastases
- •Pending visceral crisis, in the opinion of the treating investigator
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to fulvestrant or ganetespib
- •Uncontrolled intercurrent illness
- •Other malignancies within 3 years
研究组 & 干预措施
ARM A - Fulvestrant
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Eligible participants on Arm A were allowed to crossover to Arm B upon disease progression. Treatment continued for Arm A participants until 2nd disease progression.
干预措施: Fulvestrant (Drug)
Arm B - Fulvestrant+Ganetespib
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle
Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression.
干预措施: Fulvestrant (Drug)
Arm B - Fulvestrant+Ganetespib
Fulvestrant: 500 mg administered by intramuscular injection on days 1 and 15 of cycle 1, day 1 of cycle 2 and each subsequent cycle; cycle duration is 28 days Ganetespib: 200 mg/m2 administered intravenously on days 1, 8 and 15 of each 28 day cycle
Arm B participants whose disease was at a minimum stable could elect to discontinue ganetespib after 6 cycles or stay on combination treatment until disease progression. Otherwise, Arm B participants taken off ganetespib for toxicity were to remain on single agent fulvestrant until disease progression.
干预措施: Ganetespib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles longer-term. Participants in this study cohort were followed for survival up to 4 years from treatment end.
PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression (PD) or death. Participants alive without evidence of PD are censored at the date of last disease assessment. Participants who receive non-protocol anti-cancer therapy before disease progression are censored at time of last disease assessment.
次要结局
- Clinical Benefit Rate (CBR)(Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.)
- Overall Survival (OS)(Participants were followed long-term for survival every 3 months from the end of treatment until death, lost to follow-up or up to 4 years from treatment end. Median survival follow-up was 28 months for the study cohort.)
- Grade 3-4 Toxicity Rate(AEs were assessed every cycle on treatment (weeks 2-3 on cycle 1). Median treatment duration was 4 cycles/~4 months on each arm. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.)
- Objective Response Rate (ORR)(Disease was assessed radiographically every 2 cycles for year 1 and every 2-4 cycles thereafter on treatment. Maximum treatment duration was 41 cycles (Arm A) and 42 cycles (Arm B) which approximates 38 months.)
研究者
Nancy Lin, MD
Principal Investigator
Dana-Farber Cancer Institute