A Phase 3 Randomised Double-Blinded Placebo-Controlled Study of Use of GnRHa During Chemotherapy for Fertility Protection of Young Women and Teenagers With Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 500
- 试验地点
- 17
- 主要终点
- Anti-Müllerian Hormone (AMH) levels in women with breast cancer
研究概览
简要总结
Many cytotoxic drugs may harm the fertility of young women treated for cancer. The aim of the study is to investigate if the Gonadotropin-Releasing Hormone agonist (GnRHa) during cancer treatment can preserve the fertility of young female cancer subjects.
Approximately 300 women with newly diagnosed breast cancer and up to 200 women with newly diagnosed lymphoma, acute leukemias or sarcomas will be recruited before start of cancer treatment.
The patients will be randomised in between treatment with triptorelin (experimental) or placebo (control) intramuscularly a 1:1 ratio during chemotherapy. The injections may be given once monthly or once three months depending on type of chemotherapy given. Randomisation and study drug is blinded, neither investigator, research nurse nor patient will know if it is active drug or placebo. The only person who knows is the nurse preparing the injection.
Patients will be followed up to 5 years after end of treatment with physical examinations, vital signs, biochemical markers, bone mineral density exams, ultrasound for antral follicle counts and ovarian doppler flow, concomitant medications, adverse events and quality of life questionnaires.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Subjects are randomised to triptorelin (active arm) or placebo (control) given in parallel to the chemotherapy treatment for the cancer diagnosis. All personnel involved in the study, and subjects, except personnel preparing triptorelin/placebo at the local site and an unblinded monitor, will be blinded during the study. Unblinded research nurse at each site will prepare blinded triptorelin/placebo to subjects and a web-based randomisation system will be used to allocate of blinded triptorelin/placebo to subjects at randomisation and drug dispense during the treatment period.
入排标准
- 年龄范围
- 14 Years 至 42 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Breast cancer or acute leukemias, lymphomas (Hodgkin and non-Hodgkin) or sarcomas (osteo, soft tissue and Ewing) confirmed by histology and assigned for diseace-specific chemotheraphy
- •Confirmed menarche
- •ECOG performance status 0-1
- •Adequate bone marrow, renal, hepatic and cardiac functions and absence of other uncontrolled medical or psychiatric disorders
排除标准
- •Demonstrated premature ovarian failure at time of randomization according to clinical or biochemical data
- •Previous or planned bilateral oophorectomy
- •Pregnancy or breastfeeding at time of start of chemotherapy
- •Other malignancy diagnosed within the last five years
- •Uncontrolled hypertension, heart, liver, kidney related or other uncontrolled medical or psychiatric disorders including previous or current diagnosis of anorexia
- •Known osteoporosis
- •Known low platelet count with increased bleeding risk or refractory thrombocytopenia in subjects with acute leukemias
- •Known or suspected allergy against triptorelin
- •Direct radiation of the gonads previous or planned (TBI allowed)
- •Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
研究组 & 干预措施
Arm A: Triptorelin
Triptorelin given intramuscularly once every month or every third month during gonadotoxic chemotherapy treatment.
The dose is ether 11.25 mg triptorelin given for subjects having at least 3 months gonadotoxic treatment, OR 3.75 mg for subjects during one-month of gonadotoxic treatment
干预措施: Triptorelin Embonate (Drug)
Arm B: Placebo
Placebo, 0.9% sodium chloride, given intramuscularly once every month or every third month during gonadotoxic chemotherapy treatment.
The dose will be provided both as one injection compensating for 3 months' effect and one injection compensating for 1 month' effect to maintain the study blind.
干预措施: Sodium Chloride solution 0.9% (Drug)
结局指标
主要结局
Anti-Müllerian Hormone (AMH) levels in women with breast cancer
时间窗: 12 months after end of gonadotoxic chemotherapy and study drug treatment
To estimate the changes in ovarian reserve following chemotherapy for treatment of cancer with or without GnRHa by determination of the AMH relative to AMH levels at EoT in women with breast cancer.
次要结局
- Impact of use of contraceptives (yes/no) in changes of ovarian reserve with or without GnRHa(At Baseline, during treatment visits (every 1-3 months of gonadotoxic treatment), at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Impact of endocrine adjuvant therapy (yes/no) in changes of ovarian reserve with or without GnRHa(At Baseline, during treatment visits (every 1-3 months of gonadotoxic treatment), at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Anti-Müllerian Hormone (AMH) levels in women with acute leukemias, lymphomas and sarcomas.(12 months after end of gonadotoxic chemotherapy and study drug treatment)
- Changes in ovarian reserve with or without Gonadotropin-Releasing Hormone agonist (GnRHa) by determination of the antral follicle counts (AFC)(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months) and at 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT)
- Changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels(At 6 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- The proportion of females with or without GnRHa that develop ovarian insufficiency by determination of follicle stimulating hormone (FSH), inhibin and estradiol(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Impact of body mass index (BMI) (Kg/m2) on changes in ovarian reserve with or without GnRHa(At Baseline, during treatment, at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- The effect of GnRHa with or without GnRHa on ovarian blood supply(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- The proportion of females with or without GnRHa that develop amenorrhea (no menstruations)(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Pregnacy wish after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Health-related quality of life (EORTC QLQ C30)(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Health-related quality of life (FSFI)(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Health-related quality of life (HAD)(At end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months), and 6 months, 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- The development of co-morbidities during follow-up and bone mineral density(At baseline, at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months) and 12 months and 5 years after EoT)
- Disease-specific oncologic outcomes: disease-free survival(At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Disease-specific oncologic outcomes: Recurrence rate(At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
- Disease-specific oncologic outcomes: overall survival(At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.)
研究者
Kenny Rodriguez-Wallberg
Adjunct professor
Karolinska University Hospital