ProFertil

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518977-32-00

EudraCT number

2020-004780-71

ClinicalTrials.gov

NCT05328258

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To estimate the changes in ovarian reserve following chemotherapy for treatment of cancer with or without GnRHa by determination of the Anti-Müllerian Hormone (AMH) at 12 months after end of gonadotoxic treatment (EOT) in women with breast cancer.

Secondary objectives 13

1. To estimate the changes in ovarian reserve following chemotherapy for treatment of cancer with or without GnRHa by determination of the AMH at 12 months after EOT in women with acute leukemias, lymphomas and sarcomas.
2. To estimate the changes in ovarian reserve with or without GnRHa by determination of the antral follicle counts (AFC) in women with breast cancer
3. To estimate the changes in ovarian reserve with or without GnRHa by determination of the AFC in women with acute leukemias, lymphomas and sarcomas
4. To estimate the changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels in women with breast cancer
5. To estimate the changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels in women with acute leukemias, lymphomas and sarcomas
6. To compare the proportion of females with or without GnRHa that develop ovarian insufficiency by determination of follicle stimulating hormone (FSH), inhibin and estradiol at standardized timepoints
7. To investigate the impact of body mass index (BMI), use of contraceptives and endocrine adjuvant therapy in changes of ovarian reserve with or without GnRHa by longitudinal observation of AMH levels, FSH, inhibin and estradiol at standardized timepoints
8. To investigate the effect of GnRHa with or without GnRHa on ovarian blood supply
9. To estimate the proportion of females with or without GnRHa that develop amenorrhea (no menstruations)
10. To investigate fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up
11. To determine health-related quality of life (QoL) with or without GnRHa during chemotherapy and after cancer treatment
12. To study development of co-morbidities during follow-up and bone mineral density after completion of cancer treatment with or without GnRHa
13. To estimate disease-specific oncologic outcomes, recurrence rate, overall survival and disease-free survival with or without GnRHa

Conditions and MedDRA coding

Breast Cancer, Acute Leukemia, Lymphomas (Hodgkin and non-Hodgkin) ans Sarcomas (Osteo, Soft tissue and Ewing)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent
2. Age 14-42 years at cancer diagnosis
3. Female subjects with breast cancer or acute leukemias, lymphomas (Hodgkin and non-Hodgkin) or sarcomas (osteo, soft tissue and Ewing) confirmed by histology and assigned for disease-specific chemotherapy
4. Confirmed menarche
5. ECOG performance status 0-1
6. Adequate bone marrow, renal, hepatic and cardiac functions and absence of other uncontrolled medical or psychiatric disorders

Exclusion criteria 11

1. Ongoing treatment with GnRHa at baseline
2. Demonstrated premature ovarian failure at time of randomization according to clinical or biochemical data
3. Previous or planned bilateral oophorectomy
4. Pregnancy or breastfeeding at time of start of chemotherapy
5. Other malignancy diagnosed within the last five years
6. Uncontrolled hypertension, heart, liver, kidney related or other uncontrolled medical or psychiatric disorders including previous or current diagnosis of anorexia
7. Known osteoporosis
8. Known refractory thrombocytopenia in subjects with acute leukemias
9. Known or suspected allergy against triptorelin
10. Direct radiation of the gonads previous or planned (total body irradiation allowed)
11. Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The difference in recovery of AMH levels at follow-up 12 months after EoT, relative to AMH levels at EoT, as compared between the GnRHa group and the placebo group in women with breast cancer.

Secondary endpoints 11

1. The difference in recovery of AMH levels at follow-up 12 months after EoT, relative to AMH levels at EoT, between the GnRHa group and the placebo group in women with acute leukemias, lymphomas and sarcomas.
2. Comparison of AFC measured by ultrasound at EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
3. The difference in recovery of AMH levels at 6 months, and follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
4. Comparison of FSH, inhibin and estradiol performed at EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
5. Comparison of blood flow to the ovarian artery (right and left Doppler flow PI, RI) at baseline, EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
6. Comparison of the proportion that develop amenorrhea (no menstruations) at EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group:in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
7. Investigation of the impact of BMI, use of contraceptives and endocrine adjuvant therapy in changes of ovarian reserve with or without GnRHa by longitudinal observation of AMH levels, FSH, inhibin and estradiol at standardized timepoints
8. Comparison of of pregnancy wish, pregnancy attempts and pregnancy outcomes at EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
9. Comparison of health-related QoL, sexuality and reproductive health examined at EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
10. Comparison of bone mineral density at baseline, EoT and 12 months after EoT and follow-up year 5, between the GnRHa group and the placebo group: in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.
11. Investigation of recurrence rate, overall survival and disease-free survival at 12 months after EoT and follow-up years 2, 3, 4, 5 after EoT, between the GnRHa group and the placebo group:in women with breast cancer and in woman with acute leukemias, lymphomas and sarcomas.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Halsovagen, Flemingsberg Flemingsberg

City

Huddinge

Postcode

141 86

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Kenny Rodriguez-Wallberg

Public contact point

Organisation

Karolinska University Hospital

Contact name

Kenny Rodriguez-Wallberg

Locations

1 EU/EEA country · 21 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications