Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 277
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The goal of this clinical research study to find the highest tolerated dose of anastrozole alone or in combination with either everolimus (Afinitor), sorafenib (Nexavar), erlotinib (Tarceva), fulvestrant (Faslodex), or bevacizumab (Avastin) that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied.
详细描述
The Study Drugs:
Anastrozole is designed to block the last step in estrogen (a hormone) production. In estrogen-dependent tumors, anastrozole may block tumor growth.
Sorafenib is designed to block the function of a cancer protein as well as tumor blood-vessel forming proteins. It may stop the growth of blood vessels in tumors.
Bevacizumab is designed to block or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients for tumor growth.
Everolimus is designed to block cancer proteins and may block tumor growth.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients with pathologically confirmed advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have had no standard therapy that induces a CR rate of at least 10% or improves survival by at least three months.
- •Measurable or non-measurable disease
- •Patients must have tumors that demonstrate ER/PR+ (positivity by IHC staining >/= 1%).
- •At least 4 weeks since the last dose of chemotherapy, immunotherapy, surgery, or radiation therapy (Exception: patients may have received palliative low dose radiation therapy one week before treatment provided it is not given to the only targeted lesions); at least 6 weeks for therapy which is known to have delayed toxicity (nitrosoureas, mitomycin-C, and liposomal doxorubicin); at least 4 weeks (or 5 half-lives, whichever is shorter) since treatment with biologic/targeted therapies; at least 2 weeks since last hormonal therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2
- •Patients must have normal organ and marrow function defined as: absolute neutrophil count >/= 1,000/mL; platelets >/= 50,000/mL; creatinine </= 2 X ULN; total bilirubin </= 2.0; ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: total bilirubin </= 3 x ULN; ALT(SGPT) </= 5 X ULN.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days after the last dose.
- •Ability to understand and the willingness to sign a written informed consent document
- •Female patients must either be: Post-menopausal women as defined by a. age >/= 60 years of age; b. prior bilateral oophorectomy; c. age < 60 with at least 12 months of spontaneous amenorrhea or post-menopausal range FSH and estradiol levels OR Premenopausal women receiving a gonadotropin-releasing hormone agonist.
排除标准
- •Patients with uncontrolled concurrent illness, including but not limited to: ongoing or active infection; altered mental status or psychiatric illness/social situations that would limit compliance with study requirements and/or obscure study results.
- •Uncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg on medication).
- •Patients with clinically significant cardiovascular disease: history of CVA within 6 months, myocardial infarction or unstable angina within 6 months, or unstable angina pectoris.
- •Women who are pregnant or breastfeeding
- •Patients with a history of bone marrow transplant within the previous two years.
- •Patients with a known hypersensitivity to any of the components of the drug products.
- •Patients unable to swallow oral medications or with pre-existing gastrointestinal disorders that might interfere with proper absorption of oral drugs.
- •Patients with major surgery within 30 days prior to entering the study.
- •Age under 18 years.
研究组 & 干预措施
Anastrozole
1 mg PO (by mouth) daily for 28 days.
干预措施: Anastrozole (Drug)
Anastrozole + Bevacizumab
Anastrozole 1 mg PO daily and Bevacizumab starting dose 10 mg IV Day 1 of 21 day cycle. Expansion group added when MTD dose of Anastrozole + Bevacizumab found.
干预措施: Anastrozole (Drug)
Anastrozole + Bevacizumab
Anastrozole 1 mg PO daily and Bevacizumab starting dose 10 mg IV Day 1 of 21 day cycle. Expansion group added when MTD dose of Anastrozole + Bevacizumab found.
干预措施: Bevacizumab (Drug)
Anastrozole + Everolimus
Anastrozole 1 mg PO daily and Everolimus starting dose 5 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Everolimus found.
干预措施: Anastrozole (Drug)
Anastrozole + Everolimus
Anastrozole 1 mg PO daily and Everolimus starting dose 5 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Everolimus found.
干预措施: Everolimus (Drug)
Anastrozole + Sorafenib
Anastrozole 1 mg PO daily and Sorafenib starting dose 200 mg PO twice a day for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Sorafenib found.
干预措施: Anastrozole (Drug)
Anastrozole + Sorafenib
Anastrozole 1 mg PO daily and Sorafenib starting dose 200 mg PO twice a day for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Sorafenib found.
干预措施: Sorafenib (Drug)
Anastrozole + Erlotinib
Anastrozole 1 mg PO daily and Erlotinib starting dose 75 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Erlotinib found.
干预措施: Anastrozole (Drug)
Anastrozole + Erlotinib
Anastrozole 1 mg PO daily and Erlotinib starting dose 75 mg PO daily for 28 day cycle. Expansion group added when MTD dose of Anastrozole + Erlotinib found.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 28 day cycle
MTD defined as highest dose at which no more than 1 of 6 evaluable patients has had a dose limiting toxicity (DLT). Six patients should be treated before the dose is declared as MTD. DLTs defined as adverse events (AEs) related to study agents which occurs during the first cycle of treatment.
次要结局
- Tumor Response(Every 21 or 28 days depending on study group)