A multicentric open label phase II safety and efficacy study of ormeloxifene in tamoxifen resistant metastatic/recurrent breast cancer patients.
试验速览
- 阶段
- 2 期
- 状态
- Other
- 入组人数
- 56
- 试验地点
- 4
- 主要终点
- •Overall response rates (ORR) will be calculated as the proportion of patients who achieved a tumor response of partial response (PR) or complete response (CR) as per RECIST 1.1 guidelines. Data will be as number of patients (% of patients) who achieved a tumor response of partial response (PR) or complete response (CR).
研究概览
简要总结
This is a phase II study to check efficacy and safety of 120 mg oral dose of ormeloxifene in tamoxifen resistant metastatic breast cancer patients. Primary objective of the study is to evaluate clinical response rates at 16 weeks after start of treatment with 120 mg oral dose of ormeloxifene. Secondary objectives are to evaluate investigator assessed progression free survival, to evaluate clinical benefit of ormeloxifene and to study the effect of ormeloxifene on quality of life. The study will be conducted in two stages. In stage I total 23 subjects and in stage II 33 subjects will be enrolled who are falling under inclusion criteria as determined in the protocol. In stage I patients will undergo screening visit at day -7 to 0, enrolment visit at day 1, improvement visit at 60+/-2 days and end of visit at 120+/- 2 days. In stage II patients will undergo visit 0 (Day -7 to 0): screening visit, visit 1 (Day 1): Enrolment visit , visit 2 (day 30+/-2 days): Improvement visit, visit 3 (day 60+/- 2 days): Improvement visit, visit 4 (Day 120+/- 2 days): Improvement visit, visit 5 (Day 180+/-2 days): Improvement visit, visit 7 (day 360+/-2 days): Improvement visit. Assessment of parameters like radiographic tumour assessments, Laboratory assessment, health related quality of life and safety assessment will be done at visits as mentioned in the protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Not Applicable
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.Ability to provide written informed consent for participation in the study.
- •2.Female patients with ≥ 18 years, Who are either premenopausal as confirmed by no irregularities in last three consecutive menstrual periods OR serum estrogen (E2) level that is the premenopausal range.
- •OR Who were premenopausal at the time of diagnosis of breast cancer but who have undergone bilateral oophorectomy and/or radiotherapy ovarian ablation and/or gonadotropin releasing hormone agonist treatment, as part of treatment for breast cancer.
- •3.Histologically or cytologically confirmed breast cancer from most recent historical reports of histopathology.
- •4.Immunohistochemistry (IHC) evidence of estrogen receptor positive (allred score of >3/8) and IHC or FISH evidence of negative cerb B2 status.
- •5.IHC or FISH evidence for negative Cerb B2 status •In case of historical reports of IHC confirming evidence of ER-positive and Cerb B2 negative status, a repeat IHC is not required.
- •6.Patients whose cancer has evidence of tamoxifen resistance as suggested by at least one of the following: i)Development of recurrence of and/or metastasis while patient on adjuvant tamoxifen ii)Development of recurrence of and/or metastasis within one year of completing adjuvant tamoxifen.
- •iii)Progression of metastatic/recurrent disease while patient was on tamoxifen or progression of metastatic/recurrent disease within 6 months of stopping tamoxifen.
- •7.Stage I: Patient treated with not more than 2 chemotherapy regimens, including (neo) adjuvant chemo regimens.
- •8.Patients should have at least one measurable lesion as defined by RECIST criteria (version 1.1).
- •9.Patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •10.Patients with normal liver, kidney and marrow function, resolution of all toxic effects of prior therapy or surgical procedures, as per the investigator’s clinical judgement.
- •11.Life expectancy of at least 6 months in the opinion of the investigator.
排除标准
- •1.Patients with extensive advanced, symptomatic visceral disease that requires chemotherapy. 2.Patients with known uncontrolled or symptomatic CNS metastases. 3.Patients with major surgery or any anti-cancer therapy within 2 weeks prior to enrolment. 4.History of prior invasive malignancy, except breast cancer or non-melanoma skin cancer. 5.Women of childbearing potential without adequate contraception. •Unwilling to use at least one reliable method of contraception (e.g., a barrier method [condom or occlusive cap] with spermicidal foam/gel/film/cream/suppository, a non-hormone releasing intrauterine device or intrauterine system, sterilisation of sole male partner, abstinence) throughout the study period and for 6 months after the last study drug treatment. •Any continued sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement therapy during the study is not allowed. 6.Women who are pregnant or breast feeding. 7.Women in their post-menopausal state.
- •a period of continuous absence of menstrual cycles for 12 months or more as calculated at the time of screening 8.Any history of cardiac disease (history of and/or active disease) that would preclude the use of the drugs included in the treatment regimens. This includes but is not limited to: active cardiac disease.
- •angina pectoris that requires the use of anti-anginal medication; recent history of unstable angina or myocardial infarction within last 6 months, ventricular arrhythmias except for benign premature ventricular contractions; supra ventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic congestive heart failure or pericarditis; history of cardiac disease.
- •myocardial infarction documented by elevated cardiac enzymes, or a cardiac troponin or cardiac myoglobin or persistent regional wall abnormalities on assessment of left ventricular function; New York Heart Association (NYHA) class III or IV congestive heart failure; and/or documented cardiomyopathy. 9.Acute or active chronic infections which, in the opinion of the Investigator, may affect patient safety or participation in the study. 10.Known history of alcohol/drug abuse. 11.Known history of allergy to any of the study treatments. 12.History of stem cell or bone marrow transplantation. 13.Active use of potent CYP3A4 inhibitors or inducers (e.g. carbamazepine, dexamethasone and ethosuximide; cimetidine, amiodarone, azithromycin etc.). 14.Participation in any other clinical study or administration of any other investigational medications within 30 days of enrolment or 5 half- lives, whichever is longer.
结局指标
主要结局
•Overall response rates (ORR) will be calculated as the proportion of patients who achieved a tumor response of partial response (PR) or complete response (CR) as per RECIST 1.1 guidelines. Data will be as number of patients (% of patients) who achieved a tumor response of partial response (PR) or complete response (CR).
时间窗: 60±2 Days, 120±2 Days
次要结局
- (1) Clinical Benefit Rate (CBR)((2) Disease control rates)