Clinical trial NCT05328258: Use of GnRHa During Chemotherapy for Fertility Protection
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer Female
Acute Leukemia
Lymphoma
Osteosarcoma
Soft Tissue Sarcoma
Ewing Sarcoma
Keywords: Fertility protection of young women receiving chemotherapy
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2022-04-14
Enrollment: 500
Sex: FEMALE
Minimum age (years): 14
Maximum age (years): 42
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomised, double-blinded, placebo-controlled, phase 3 study
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Anti-Müllerian Hormone (AMH) levels in women with breast cancer
timeFrame: 12 months after end of gonadotoxic chemotherapy and study drug treatment
Secondary outcomes:
measure: Anti-Müllerian Hormone (AMH) levels in women with acute leukemias, lymphomas and sarcomas.
timeFrame: 12 months after end of gonadotoxic chemotherapy and study drug treatment
measure: Changes in ovarian reserve with or without Gonadotropin-Releasing Hormone agonist (GnRHa) by determination of the antral follicle counts (AFC)
timeFrame: 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
measure: Changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels
timeFrame: At 6 months, 2 years, 3 years, 4 years and 5 years after EoT.
measure: The proportion of females with or without GnRHa that develop ovarian insufficiency by determination of follicle stimulating hormone (FSH), inhibin and estradiol
timeFrame: 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.
measure: Impact of body mass index (BMI) (Kg/m2) on changes in ovarian reserve with or without GnRHa
timeFrame: 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.
measure: Impact of use of contraceptives (yes/no) in changes of ovarian reserve with or without GnRHa
timeFrame: 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.
measure: Impact of endocrine adjuvant therapy (yes/no) in changes of ovarian reserve with or without GnRHa
timeFrame: 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.
measure: The effect of GnRHa with or without GnRHa on ovarian blood supply
timeFrame: 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.
measure: The proportion of females with or without GnRHa that develop amenorrhea (no menstruations)
timeFrame: 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.
measure: Pregnacy wish after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up
timeFrame: 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.
measure: Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up
timeFrame: 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.
measure: Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up
timeFrame: 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.
measure: Health-related quality of life (EORTC QLQ C30)
timeFrame: 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.
measure: Health-related quality of life (FSFI)
timeFrame: 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.
measure: Health-related quality of life (HAD)
timeFrame: 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.
measure: The development of co-morbidities during follow-up and bone mineral density
timeFrame: At baseline, at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months) and 12 months and 5 years after EoT
measure: Disease-specific oncologic outcomes: disease-free survival
timeFrame: At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.
measure: Disease-specific oncologic outcomes: Recurrence rate
timeFrame: At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.
measure: Disease-specific oncologic outcomes: overall survival
timeFrame: At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.
Other outcomes:
Locations:
city: Göteborg
country: Sweden
facility: Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth
city: Göteborg
country: Sweden
facility: Center for Pediatric Oncology, Akademiska Hospital
city: Göteborg
country: Sweden
facility: Department of Oncology, Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Department of Hematology, Skåne University Hospital
city: Lund
country: Sweden
facility: Department of Oncology, Skåne University Hospital
city: Lund
country: Sweden
facility: Department of Pediatric Oncology, Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska Univeristy Hospital, Breast Centre
city: Stockholm
country: Sweden
facility: Department of Hematology and coagulation, Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Department of Hematology, Capio ST. Göran Hospital
city: Stockholm
country: Sweden
facility: Department of Internal Medicine, Södersjukhuset
city: Stockholm
country: Sweden
facility: Department of Oncology, Capio ST. Göran Hospital
city: Stockholm
country: Sweden
facility: Department of Oncology, Södersjukhuset
city: Stockholm
country: Sweden
facility: Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Hematology
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, High Specialised Pediatric Medicine
city: Umeå
country: Sweden
facility: Department of Oncology, Norrlands University Hospital
city: Örebro
country: Sweden
facility: Department of Oncology, Örebro University Hospital
Study officials:
References: