A Phase II TRIal evalUating the Menstrual and Ovarian Function of Young Breast Cancer Patients Treated With a cycloPHosphamide-free Regimen Composed of Doxorubicin and Paclitaxel
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Change from baseline in menstrual function
研究概览
简要总结
Recently, there has been a rising trend of delaying childbearing and hence more women are diagnosed with breast cancer before completing their families. Given the continuous decline in recurrences and death secondary to breast cancer and the reassuring data on the safety of pregnancy following breast cancer more women are inquiring into the possibility of preserving fertility following chemotherapy. The challenge remains in using a regimen that is devoid of cyclophosphamide, but is as effective as the standard regimens that incorporate cyclophosphamide. The combination doxorubicin (50 mg/m2) and paclitaxel (200 mg/m2) (AP) followed by 12 weeks of paclitaxel (80 mg/m2) (P) emerges as a treatment option with convincing results regarding its effectiveness in the early setting, and could be potentially associated with less ovarian toxicity being devoid of cyclophosphamide.
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 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age ≤ 40 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Non-metastatic primary invasive carcinoma of the breast eligible for adjuvant or neoadjuvant chemotherapy.
- •Negative estrogen (ER) and progesterone receptor (PgR) status.
- •Baseline left ventricular ejection fraction (LVEF) ≥50% measured by an echocardiogram or MUGA.
- •Interested in maintaining menstrual and/or ovarian function following completion of chemotherapy.
- •Known HER2/neu status.
- •Negative pregnancy test within 14 days prior to starting chemotherapy.
- •Adequate hematologic, hepatic and renal function.
- •Signed informed consent.
排除标准
- •History of prior malignant disease (breast or non-breast) or non-malignant condition which was treated with chemotherapy, pelvic irradiation or any therapy that could potentially affect ovarian function.
- •Previous history of amenorrhea > 3 months within the last 2 years (excluding pregnancy).
- •Ovarian insufficiency defined as serum FSH > 20 IU/L at the local laboratory, anytime during the menstrual cycle.
- •Any ovarian pathology or abnormalities at the screening pelvic ultrasound, except for functional follicular cysts.
- •Pregnant or breastfeeding patients.
- •Inability or unwillingness to use effective contraception during and up to 3 months after the last dose of study medication. Effective methods include the following: non-hormonal intrauterine device, barrier method - condoms, diaphragm - also in conjugation with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed.
- •Concurrent use of any other cytotoxic or hormonal agent, namely GnRH agonists.
- •Prior pre-existing peripheral neuropathy of any cause, including diabetes mellitus, alcohol abuse, HIV infection, autoimmune and hereditary neuropathies, amyloidosis, hypothyroidism, vitamin deficiencies.
- •Serious cardiac illness, uncontrolled hypertension or medical condition that would affect administration of chemotherapy and compliance to study procedures.
- •Known sensitivity to any of the study medications.
研究组 & 干预措施
doxorubicin and paclitaxel
All patients will receive four cycles of doxorubicin (A) (50 mg/m2) and paclitaxel (P) (200 mg/m2), given on a three-weekly basis for four cycles, followed by weekly paclitaxel (P) (80 mg/m2) for twelve weeks.
干预措施: Doxorubicin (Drug)
doxorubicin and paclitaxel
All patients will receive four cycles of doxorubicin (A) (50 mg/m2) and paclitaxel (P) (200 mg/m2), given on a three-weekly basis for four cycles, followed by weekly paclitaxel (P) (80 mg/m2) for twelve weeks.
干预措施: paclitaxel (Drug)
结局指标
主要结局
Change from baseline in menstrual function
时间窗: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
Menstrual function will be evaluated by collecting information of the 1st day of last menstrual cycle, and cycle length (days between two menstruating periods). In patients menstruating regularly after 12 months of chemotherapy cessation, information on menstrual cycle will be collected at 6-monthly intervals until developing menopause, disease recurrence, becoming pregnant, whichever occurs earlier, for a maximum period of 5 years after end of chemotherapy.
Change from baseline in ovarian function
时间窗: At screening, after 4 cycles of chemotherapy, at the end of chemotherapy, at 6, 12, 18 and 24 months following chemotherapy
Ovarian function will be evaluated using serum FSH, estradiol and AMH. Ovarian failure is defined as serum FSH \>40 IU/L. Ovarian insufficiency is defined as serum FSH level from 20 - 40 IU/L. Ovarian reserve will be evaluated by serum AMH. Adequate ovarian reserve is defined as serum AMH \>1 ng/ml. Menstrual function will be evaluated by collecting information of the 1st day of last menstrual cycle, and cycle length (days between two menstruating periods). Ovarian function will be evaluated using serum FSH, estradiol and AMH. Ovarian failure is defined as serum FSH \>40 IU/L. Ovarian insufficiency is defined as serum FSH level from 20 - 40 IU/L. Ovarian reserve will be evaluated by serum AMH. Adequate ovarian reserve is defined as serum AMH \>1 ng/ml.
次要结局
- Impact of treatment on the behavior of menstruation after menses resumption(At 18, 24 and 60 months after end of chemotherapy.)
- Evaluate the impact of a cyclophosphamide-free regimen on sexual function(At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.)
- Evaluate the impact of the regimen on peripheral neurotoxicity(At baseline, after 4 cycles, end of chemotherapy, 6, 12 and 24 months following the end of chemotherapy.)
- Event-free survival(From the date of registration up until 60 months after the end of chemotherapy.)
- Ovarian reserve(At 12 months following the end of chemotherapy.)
- Occurence of Adverse Events(From the signature of informed consent until until the end of study treatment/treatment discontinuation visit 30 days after the last dose of study medication)
- Pregnancy rate after cessation of chemotherapy(From end of chemotherapy up until 60 months after.)