ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study
Background Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa...
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BMJ Publishing Group
2023-12-01
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| Online Access: | https://bmjopen.bmj.com/content/13/12/e078023.full |
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| author | Kenny A Rodriguez-Wallberg Jonas Bergh Antonis Valachis Per Frisk Theodoros Foukakis Per Ljungman Sandra Eloranta Hanna Pauline Nilsson Johan Malmros Christina Linder Stragliotto Erika Isaksson Friman Barbro Linderholm Anne Andersson Sara Harrysson Lovisa Vennström Helena Mörse |
| author_facet | Kenny A Rodriguez-Wallberg Jonas Bergh Antonis Valachis Per Frisk Theodoros Foukakis Per Ljungman Sandra Eloranta Hanna Pauline Nilsson Johan Malmros Christina Linder Stragliotto Erika Isaksson Friman Barbro Linderholm Anne Andersson Sara Harrysson Lovisa Vennström Helena Mörse |
| author_sort | Kenny A Rodriguez-Wallberg |
| collection | DOAJ |
| description | Background Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.Methods and analysis A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.Ethics and dissemination This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.Study registration The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.Trial registration number NCT05328258; EudraCT number:2020-004780-71. |
| format | Article |
| id | doaj-art-ba5924fc50df467589005f382b3a4808 |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2023-12-01 |
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| spelling | doaj-art-ba5924fc50df467589005f382b3a48082025-08-20T03:11:10ZengBMJ Publishing GroupBMJ Open2044-60552023-12-01131210.1136/bmjopen-2023-078023ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled studyKenny A Rodriguez-Wallberg0Jonas Bergh1Antonis Valachis2Per Frisk3Theodoros Foukakis4Per Ljungman5Sandra Eloranta6Hanna Pauline Nilsson7Johan Malmros8Christina Linder Stragliotto9Erika Isaksson Friman10Barbro Linderholm11Anne Andersson12Sara Harrysson13Lovisa Vennström14Helena Mörse15Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institute, Stockholm, SwedenOncology, Örebro universitet Fakulteten för medicin och hälsa, Orebro, SwedenAkademiska Hospital, Uppsala, SwedenDepartment of Oncology-Pathology, Karolinska Institute, Stockholm, SwedenDepartment of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine, Karolinska Institute, Solna, SwedenDepartment of Oncology-Pathology, Karolinska Institute, Stockholm, SwedenPediatric Theme Astrid Lindgren`s Pediatric Hospital, Stockholm, SwedenTheme cancer, Karolinska Comprehensive Cancer Center and University Hospital, Stockholm, SwedenDepartment of Oncology, Capio ST, Göran Hospital, Stockholm, SwedenDepartment of Oncology, Sahlgrenska University Hospital, Goteborg, SwedenDepartment of Oncology, Norrlands University Hospital, Umeå, SwedenDepartment of Hematology, Cancer Theme, Karolinska University Hospital, Stockholm, SwedenDepartment of Hematology and Coagulation, Sahlgrenska University Hospital, Goteborg, SwedenCenter for Pediatric Oncology, Skåne University Hospital, Lund, SwedenBackground Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.Methods and analysis A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.Ethics and dissemination This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.Study registration The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.Trial registration number NCT05328258; EudraCT number:2020-004780-71.https://bmjopen.bmj.com/content/13/12/e078023.full |
| spellingShingle | Kenny A Rodriguez-Wallberg Jonas Bergh Antonis Valachis Per Frisk Theodoros Foukakis Per Ljungman Sandra Eloranta Hanna Pauline Nilsson Johan Malmros Christina Linder Stragliotto Erika Isaksson Friman Barbro Linderholm Anne Andersson Sara Harrysson Lovisa Vennström Helena Mörse ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study BMJ Open |
| title | ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study |
| title_full | ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study |
| title_fullStr | ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study |
| title_full_unstemmed | ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study |
| title_short | ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden—a phase III randomised double-blinded placebo-controlled study |
| title_sort | profertil study protocol for the investigation of gonadotropin releasing hormone agonists gnrha during chemotherapy aiming at fertility protection of young women and teenagers with cancer in sweden a phase iii randomised double blinded placebo controlled study |
| url | https://bmjopen.bmj.com/content/13/12/e078023.full |
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