ProFertil: A Randomised Placebo-Controlled Study of Use of GnRHa During Chemotherapy for Fertility Protection of Young Women With Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Triptorelin Embonate
11.25 mg will be given for subjects having at least 3 months gonadotoxic treatment, one injection of 11.25 mg will compensate for 3 months' effect of the study drug.
3.75 mg will be given for subjects during one-month of gonadotoxic treatment, one injection of 3.75 mg will compensate for 1 month' effect of the study drug.
Other Names:
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| Placebo Comparator: 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. |
Drug: Sodium Chloride solution 0.9%
One injection compensating for 3 months' effect OR one injection compensating for 1 month' effect to maintain the study blind.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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, 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, 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 chemotherapy (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 attempts (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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Signed informed consent
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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
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Confirmed menarche
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ECOG performance status 0-1
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Adequate bone marrow, renal, hepatic and cardiac functions and absence of other uncontrolled medical or psychiatric disorders
Exclusion Criteria:
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Demonstrated premature ovarian failure at time of randomization according to clinical or biochemical data
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Previous or planned bilateral oophorectomy
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Pregnancy or breastfeeding at time of start of chemotherapy
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Other malignancy diagnosed within the last five years
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Uncontrolled hypertension, heart, liver, kidney related or other uncontrolled medical or psychiatric disorders including previous or current diagnosis of anorexia
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Known osteoporosis
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Known low platelet count with increased bleeding risk or refractory thrombocytopenia in subjects with acute leukemias
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Known or suspected allergy against triptorelin
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Direct radiation of the gonads previous or planned (TBI allowed)
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Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth | Göteborg | Sweden | ||
| 2 | Center for Pediatric Oncology, Akademiska Hospital | Göteborg | Sweden | ||
| 3 | Department of Oncology, Sahlgrenska University Hospital | Göteborg | Sweden | ||
| 4 | Department of Hematology, Skåne University Hospital | Lund | Sweden | ||
| 5 | Department of Oncology, Skåne University Hospital | Lund | Sweden | ||
| 6 | Department of Pediatric Oncology, Skåne University Hospital | Lund | Sweden | ||
| 7 | Karolinska Univeristy Hospital, Breast Centre | Stockholm | Sweden | 17176 | |
| 8 | Department of Hematology and coagulation, Sahlgrenska University Hospital | Stockholm | Sweden | ||
| 9 | Department of Hematology, Capio ST. Göran Hospital | Stockholm | Sweden | ||
| 10 | Department of Internal Medicine, Södersjukhuset | Stockholm | Sweden | ||
| 11 | Department of Oncology, Capio ST. Göran Hospital | Stockholm | Sweden | ||
| 12 | Department of Oncology, Södersjukhuset | Stockholm | Sweden | ||
| 13 | Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet | Stockholm | Sweden | ||
| 14 | Karolinska University Hospital, Hematology | Stockholm | Sweden | ||
| 15 | Karolinska University Hospital, High Specialised Pediatric Medicine | Stockholm | Sweden | ||
| 16 | Department of Oncology, Norrlands University Hospital | Umeå | Sweden | ||
| 17 | Department of Oncology, Örebro University Hospital | Örebro | Sweden |
Sponsors and Collaborators
- Kenny Rodriguez-Wallberg
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ProFertil