Use of GnRHa During Chemotherapy for Fertility Protection
- Conditions
- Breast Cancer FemaleAcute LeukemiaLymphomaOsteosarcomaSoft Tissue SarcomaEwing Sarcoma
- Interventions
- Drug: Sodium Chloride solution 0.9%
- Registration Number
- NCT05328258
- Lead Sponsor
- Kenny Rodriguez-Wallberg
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 500
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Placebo Sodium Chloride solution 0.9% 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. Arm A: Triptorelin Triptorelin Embonate 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
- Primary Outcome Measures
Name Time Method Anti-Müllerian Hormone (AMH) levels in women with breast cancer 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.
- Secondary Outcome Measures
Name Time Method Anti-Müllerian Hormone (AMH) levels in women with acute leukemias, lymphomas and sarcomas. 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 acute leukemias, lymphomas and sarcomas.
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 AFC in women with breast cancer and with acute leukemia, lymphoma and sarcoma respectively
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 difference in recovery of AMH levels between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively
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. Comparison of FSH, inhibin and estradiol between the GnRHa group and the placebo group
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. longitudinal observation of AMH levels, FSH, inhibin and estradiol
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. longitudinal observation of AMH levels, FSH, inhibin and estradiol
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. longitudinal observation of AMH levels, FSH, inhibin and estradiol
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. Comparison of blood flow to the ovarian artery (right and left Doppler flow) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively
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. Comparison of the proportion that develop amenorrhea (no menstruations) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively
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. Comparison of of pregnancy wish (Study specific questionaire) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
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. Comparison of pregnancy outcome between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
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. Comparison of validated outcome on health-related QoL (EORTC QLQ C30) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
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. Comparison of validated outcome of sexuality and reproductive health (Female Sexual Function Index (FSFI)) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
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. Comparison of validated outcome on health-related QoL (Hospital Anxiety and Depression Scale (HAD)) between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
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 Comparison of bone mineral density between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
Disease-specific oncologic outcomes: disease-free survival At 12 months, 2 years, 3 years, 4 years and 5 years after EoT. Investigation of disease-free survival between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
Disease-specific oncologic outcomes: Recurrence rate At 12 months, 2 years, 3 years, 4 years and 5 years after EoT. Investigation of recurrence rate between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
Disease-specific oncologic outcomes: overall survival At 12 months, 2 years, 3 years, 4 years and 5 years after EoT. Investigation of overall survival between the GnRHa group and the placebo group in women with breast cancer and in women with acute leukemia, lymphoma and sarcoma respectively.
Trial Locations
- Locations (17)
Karolinska Univeristy Hospital, Breast Centre
🇸🇪Stockholm, Sweden
Department of Oncology, Skåne University Hospital
🇸🇪Lund, Sweden
Karolinska University Hospital, Hematology
🇸🇪Stockholm, Sweden
Department of Oncology, Sahlgrenska University Hospital
🇸🇪Göteborg, Sweden
Department of Hematology, Capio ST. Göran Hospital
🇸🇪Stockholm, Sweden
Department of Oncology, Örebro University Hospital
🇸🇪Örebro, Sweden
Department of Oncology, Capio ST. Göran Hospital
🇸🇪Stockholm, Sweden
Department of Oncology, Södersjukhuset
🇸🇪Stockholm, Sweden
Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet
🇸🇪Stockholm, Sweden
Department of Oncology, Norrlands University Hospital
🇸🇪Umeå, Sweden
Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth
🇸🇪Göteborg, Sweden
Center for Pediatric Oncology, Akademiska Hospital
🇸🇪Göteborg, Sweden
Department of Hematology, Skåne University Hospital
🇸🇪Lund, Sweden
Department of Hematology and coagulation, Sahlgrenska University Hospital
🇸🇪Stockholm, Sweden
Department of Pediatric Oncology, Skåne University Hospital
🇸🇪Lund, Sweden
Department of Internal Medicine, Södersjukhuset
🇸🇪Stockholm, Sweden
Karolinska University Hospital, High Specialised Pediatric Medicine
🇸🇪Stockholm, Sweden