Use of GnRHa During Chemotherapy for Fertility Protection

Lymphoma Clinical Trial

— ProFertil  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05328258
• Other study ID #: ProFertil
• Status: Recruiting
• Phase: Phase 3
• Start date: March 31, 2023
• Est. completion date: January 31, 2032

Study information

• Verified date: October 2023
• Source: Karolinska University Hospital
• Contact: Kenny Rodriguez Wallberg, MD, PhD
• Phone: +46 858580000
• Email: kenny.rodriguez-wallberg[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 31, 2032
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 14 Years to 42 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Leukemia
• Breast Cancer Female
• Ewing Sarcoma
• Lymphoma
• Osteosarcoma
• Sarcoma
• Sarcoma, Ewing
• Soft Tissue Sarcoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Sweden	Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth	Göteborg
Sweden	Center for Pediatric Oncology, Akademiska Hospital	Göteborg
Sweden	Department of Oncology, Sahlgrenska University Hospital	Göteborg
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	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 Univeristy Hospital, Breast Centre	Stockholm
Sweden	Karolinska University Hospital, Hematology	Stockholm
Sweden	Karolinska University Hospital, High Specialised Pediatric Medicine	Stockholm
Sweden	Department of Oncology, Norrlands University Hospital	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
Kenny Rodriguez-Wallberg

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Anti-Müllerian Hormone (AMH) levels in women with acute leukemias, lymphomas and sarcomas.	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.	12 months after end of gonadotoxic chemotherapy and study drug treatment
Secondary	Changes in ovarian reserve with or without Gonadotropin-Releasing Hormone agonist (GnRHa) by determination of the antral follicle counts (AFC)	Changes in AFC in women with breast cancer and with acute leukemia, lymphoma and sarcoma respectively	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
Secondary	Changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels	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	At 6 months, 2 years, 3 years, 4 years and 5 years after EoT.
Secondary	The proportion of females with or without GnRHa that develop ovarian insufficiency by determination of follicle stimulating hormone (FSH), inhibin and estradiol	Comparison of FSH, inhibin and estradiol between the GnRHa group and the placebo group	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.
Secondary	Impact of body mass index (BMI) (Kg/m2) on changes in ovarian reserve with or without GnRHa	longitudinal observation of AMH levels, FSH, inhibin and estradiol	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.
Secondary	Impact of use of contraceptives (yes/no) in changes of ovarian reserve with or without GnRHa	longitudinal observation of AMH levels, FSH, inhibin and estradiol	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.
Secondary	Impact of endocrine adjuvant therapy (yes/no) in changes of ovarian reserve with or without GnRHa	longitudinal observation of AMH levels, FSH, inhibin and estradiol	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.
Secondary	The effect of GnRHa with or without GnRHa on ovarian blood supply	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	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.
Secondary	The proportion of females with or without GnRHa that develop amenorrhea (no menstruations)	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	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.
Secondary	Pregnacy wish after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up	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.	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.
Secondary	Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up	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.	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.
Secondary	Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up	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.	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.
Secondary	Health-related quality of life (EORTC QLQ C30)	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.	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.
Secondary	Health-related quality of life (FSFI)	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.	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.
Secondary	Health-related quality of life (HAD)	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.	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.
Secondary	The development of co-morbidities during follow-up and bone mineral density	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.	At baseline, at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months) and 12 months and 5 years after EoT
Secondary	Disease-specific oncologic outcomes: disease-free survival	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.	At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.
Secondary	Disease-specific oncologic outcomes: Recurrence rate	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.	At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.
Secondary	Disease-specific oncologic outcomes: overall survival	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.	At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.