Phase II Study of The Efficacy And Safety of Chloroquine (C) in CombinAtion With Taxane or Taxane-like (T) Chemo Agents in The Treatment of Patients With Advanced or Metastatic Breast Cancer Who Have Failed Anthracycline Chemo Base Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 3
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The major purpose of this research study is to better understand how therapy works on different patients. This study is being offered to patients with a diagnosis of advanced or metastatic breast cancer who have failed anthracycline based therapy.
The investigators want to see the response of breast cancer cell when treated with Chloroquine used in combination with chemotherapy. Chemotherapy is an anti-cancer drug that is given through your vein. The chemotherapy used in this study is either Taxane (Paclitaxel) or Taxane-like drugs (Abraxane, Ixabepilone or Docetaxel).
详细描述
The purpose of this study is to determine the anti-tumor activity of the combination of Chloroquine combined with a Taxane or Taxane-like chemo agents(Paclitaxel, Docetaxel, Abraxane, Ixabepilone).
The laboratories have developed robust preclinical models utilizing both in vitro systems such as the mammosphere (MS) culture and in vivo systems such as human breast cancer xenografts allowing the investigators to identify agents which selectively target TICs, as single agents or in combination. These models are critical since tumor initiating cells (TICs) comprise only a small percentage of the tumor bulk, so that clinical tumor regression may not be observed with inhibitors that selectively target TIC self-renewal alone. Nonetheless, these agents in combination with conventional therapy may effectively kill both actively cycling or fully differentiated cells and the TIC subpopulation, leading to long term remission and eradication of cancer cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Females with pathologically determined advanced or metastatic breast cancer.
- •Have progressed after treatment with regimen that included an anthracycline.
- •Have had at least 4 cycles of an anthracycline containing regimen or 2 cycles if progressing on treatment.
- •Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors.
- •≥18 years of age.
- •ECOG PS of 0, 1, or
- •Laboratory values within the following ranges:
- •Hemoglobin ≥9.0gm/dL (≥1.5μmol/L); transfusions permitted.
- •Absolute neutrophil count ≥1500/mm3 (1.5 x 109/L)
- •Platelet count ≥100,000/mm3 (100 x 109/L)
- •Creatinine (Cr) <2 X the upper limit of normal (ULN), Cr clearance (CrCl) ≥30 by Cockcroft and Gault
- •Alanine aminotransferase and aspartate aminotransferase <2 X the ULN; if liver metastases are present then must be <5 X the ULN, Bilirubin <2 X the ULN, Potassium within normal limits, Magnesium within normal limits
- •Negative serum pregnancy test at the time of first dose for women of childbearing potential (WOCBP). For WOCBP, adequate contraception must be used throughout the study. For this study, acceptable methods of contraception include a reliable intrauterine device or a spermicide in combination with a barrier method. Women who are already on hormonal forms of birth control may continue that treatment but must also use a barrier method.
- •Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments.
- •Patient must be willing to undergo breast biopsies as required by the study protocol.
排除标准
- •Radiation therapy within 2 weeks; or chemotherapy or non-cytotoxic investigational agents within 4 weeks of initiating study treatment.
- •Evidence of New York Heart Association class III or greater cardiac disease.
- •History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months.
- •History of congenital QT prolongation.
- •Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study.
- •Symptomatic central nervous system metastases. The patient must be stable after radiotherapy for ≥2 weeks and off corticosteroids for ≥1 week.
- •Pregnant or nursing women.
- •Hypersensitivity or intolerance to Chloroquine, Paclitaxel, Docetaxel, Abraxane, Ixabepilone or other Taxane like drugs.
- •Severe renal insufficiency (CrCl <30mL/min [Cockcroft and Gault]).
- •History of gastrointestinal bleeding, ulceration, or perforation.
- •Concurrent use of potent CYP3A4 inhibitors, such as ketoconazole, itraconazole,clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole.
- •Concurrent use of potent CYP3A4 inducers, such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbitol, and St. John's wort.
研究组 & 干预措施
Chloroquine with Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) fro a maximum of 6 cycles.
干预措施: Paclitaxel (Drug)
Chloroquine with Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) fro a maximum of 6 cycles.
干预措施: Docetaxel (Drug)
Chloroquine with Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) fro a maximum of 6 cycles.
干预措施: Abraxane (Drug)
Chloroquine with Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) fro a maximum of 6 cycles.
干预措施: Ixabepilone (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 3-week cycles for maximum of 6 cycles (4.5 months)
To determine the anti-tumor activity of the combination of Chloroquine + Taxane or Taxane-like chemo agents (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) (C/T) measured by overall Response Rate (ORR) defined as percentage of patients having complete or partial response in therapy per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate. The study was designed to compare the ORR with the published percentage of 30% (docetaxel 100 mg/ml2 every 3 weeks for maximum of 10 cycles).
次要结局
- Time of Overall Survival (OS)(a median of 25.4 months, up to 83.5 months)
- Time to Progression Free Survival (PFS)(25.4 months (median))
- Number of Patients Who Experienced Grade 3 of Greater Adverse Events(25.4 months (median))
研究者
Jenny C. Chang, MD
Principal Investigator
The Methodist Hospital Research Institute