Use of GnRHa During Chemotherapy for Fertility Protection
ProFertil
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
1 other identifier
interventional
500
1 country
17
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2023
Longer than P75 for phase_3
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2022
CompletedFirst Posted
Study publicly available on registry
April 14, 2022
CompletedStudy Start
First participant enrolled
March 31, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2032
October 27, 2023
October 1, 2023
4.8 years
March 29, 2022
October 25, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Anti-Müllerian Hormone (AMH) levels in women with breast cancer
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.
12 months after end of gonadotoxic chemotherapy and study drug treatment
Secondary Outcomes (19)
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.
- +14 more secondary outcomes
Study Arms (2)
Arm A: Triptorelin
EXPERIMENTALTriptorelin 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
Arm B: Placebo
PLACEBO COMPARATORPlacebo, 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.
Interventions
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.
One injection compensating for 3 months' effect OR one injection compensating for 1 month' effect to maintain the study blind.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth
Gothenburg, Sweden
Center for Pediatric Oncology, Akademiska Hospital
Gothenburg, Sweden
Department of Oncology, Sahlgrenska University Hospital
Gothenburg, Sweden
Department of Hematology, Skåne University Hospital
Lund, Sweden
Department of Oncology, Skåne University Hospital
Lund, Sweden
Department of Pediatric Oncology, Skåne University Hospital
Lund, Sweden
Department of Oncology, Örebro University Hospital
Örebro, Sweden
Karolinska Univeristy Hospital, Breast Centre
Stockholm, 17176, Sweden
Department of Hematology and coagulation, Sahlgrenska University Hospital
Stockholm, Sweden
Department of Hematology, Capio ST. Göran Hospital
Stockholm, Sweden
Department of Internal Medicine, Södersjukhuset
Stockholm, 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
Karolinska University Hospital, Hematology
Stockholm, Sweden
Karolinska University Hospital, High Specialised Pediatric Medicine
Stockholm, Sweden
Department of Oncology, Norrlands University Hospital
Umeå, Sweden
Related Publications (1)
Rodriguez-Wallberg KA, Nilsson HP, Bergh J, Malmros J, Ljungman P, Foukakis T, Stragliotto CL, Friman EI, Linderholm B, Valachis A, Andersson A, Harrysson S, Vennstrom L, Frisk P, Morse H, Eloranta S. 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. 2023 Dec 9;13(12):e078023. doi: 10.1136/bmjopen-2023-078023.
PMID: 38070906DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- 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.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Adjunct professor
Study Record Dates
First Submitted
March 29, 2022
First Posted
April 14, 2022
Study Start
March 31, 2023
Primary Completion (Estimated)
January 1, 2028
Study Completion (Estimated)
January 31, 2032
Last Updated
October 27, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share
The identity of the individual participants is protected by GDPR through the The Swedish Authority for Privacy Protection as regulated by the informed consent and any data sharing must be in accordance with their regulations. We can thus only share IPD that underlie the results reported in this study (text, tables, figures, and appendices), after full anonymization of the data. After completion of the study the protocol, informed consent form and statistical analysis plan will be available. Requests for additional analyses or to access the anonymized datasets should be directed to kenny.rodriguez-wallberg@ki.se. Information will be available upon reasonable request to the sponsor and if in correspondence with the proposed research in the signed informed consent e.g to achieve aims in the approved proposal.