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Use of GnRHa During Chemotherapy for Fertility Protection (ProFertil)

Primary Purpose

Breast Cancer Female, Acute Leukemia, Lymphoma

Status

Not yet recruiting

Phase

Phase 3

Locations

Sweden

Study Type

Interventional

Intervention

Triptorelin Embonate

Sodium Chloride solution 0.9%

About this trial

This is an interventional treatment trial for Breast Cancer Female focused on measuring Fertility protection of young women receiving chemotherapy

Eligibility Criteria

14 Years - 42 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth
Center for Pediatric Oncology, Akademiska Hospital
Department of Oncology, Sahlgrenska University Hospital
Department of Hematology, Skåne University Hospital
Department of Oncology, Skåne University Hospital
Department of Pediatric Oncology, Skåne University Hospital
Karolinska Univeristy Hospital, Breast Centre
Department of Hematology and coagulation, Sahlgrenska University Hospital
Department of Hematology, Capio ST. Göran Hospital
Department of Internal Medicine, Södersjukhuset
Department of Oncology, Capio ST. Göran Hospital
Department of Oncology, Södersjukhuset
Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet
Karolinska University Hospital, Hematology
Karolinska University Hospital, High Specialised Pediatric Medicine
Department of Oncology, Norrlands University Hospital
Department of Oncology, Örebro University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm A: Triptorelin

Arm B: Placebo

Arm Description

Triptorelin 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

Placebo, 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

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

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

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

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

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05328258

First Posted

March 29, 2022

Last Updated

March 6, 2023

Sponsor

Kenny Rodriguez-Wallberg

1. Study Identification

Unique Protocol Identification Number

NCT05328258

Brief Title

Use of GnRHa During Chemotherapy for Fertility Protection

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

March 31, 2023 (Anticipated)

Primary Completion Date

January 1, 2028 (Anticipated)

Study Completion Date

January 31, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Kenny Rodriguez-Wallberg

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Fertility protection of young women receiving chemotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Prospective, randomised, double-blinded, placebo-controlled, phase 3 study

Masking

ParticipantCare ProviderInvestigator

Masking Description

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.

Allocation

Randomized

Enrollment

500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A: Triptorelin

Arm Type

Experimental

Arm Description

Arm Title

Arm B: Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Triptorelin Embonate

Other Intervention Name(s)

Pamorelin

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Sodium Chloride solution 0.9%

Other Intervention Name(s)

Placebo

Intervention Description

One injection compensating for 3 months' effect OR one injection compensating for 1 month' effect to maintain the study blind.

Primary Outcome Measure Information:

Title

Anti-Müllerian Hormone (AMH) levels in women with breast cancer

Description

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.

Time Frame

12 months after end of gonadotoxic chemotherapy and study drug treatment

Secondary Outcome Measure Information:

Title

Anti-Müllerian Hormone (AMH) levels in women with acute leukemias, lymphomas and sarcomas.

Description

Time Frame

12 months after end of gonadotoxic chemotherapy and study drug treatment

Title

Changes in ovarian reserve with or without Gonadotropin-Releasing Hormone agonist (GnRHa) by determination of the antral follicle counts (AFC)

Description

Changes in AFC in women with breast cancer and with acute leukemia, lymphoma and sarcoma respectively

Time Frame

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

Title

Changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels

Description

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

Time Frame

At 6 months, 2 years, 3 years, 4 years and 5 years after EoT.

Title

The proportion of females with or without GnRHa that develop ovarian insufficiency by determination of follicle stimulating hormone (FSH), inhibin and estradiol

Description

Comparison of FSH, inhibin and estradiol between the GnRHa group and the placebo group

Time Frame

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.

Title

Impact of body mass index (BMI) (Kg/m2) on changes in ovarian reserve with or without GnRHa

Description

longitudinal observation of AMH levels, FSH, inhibin and estradiol

Time Frame

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.

Title

Impact of use of contraceptives (yes/no) in changes of ovarian reserve with or without GnRHa

Description

longitudinal observation of AMH levels, FSH, inhibin and estradiol

Time Frame

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.

Title

Impact of endocrine adjuvant therapy (yes/no) in changes of ovarian reserve with or without GnRHa

Description

longitudinal observation of AMH levels, FSH, inhibin and estradiol

Time Frame

Title

The effect of GnRHa with or without GnRHa on ovarian blood supply

Description

Time Frame

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.

Title

The proportion of females with or without GnRHa that develop amenorrhea (no menstruations)

Description

Time Frame

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.

Title

Pregnacy wish after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up

Description

Time Frame

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.

Title

Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up

Description

Time Frame

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.

Title

Fertility and childbirth after cancer treatment in women with or without GnRHa who attempt pregnancy during follow-up

Description

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.

Time Frame

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.

Title

Health-related quality of life (EORTC QLQ C30)

Description

Time Frame

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.

Title

Health-related quality of life (FSFI)

Description

Time Frame

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.

Title

Health-related quality of life (HAD)

Description

Time Frame

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.

Title

The development of co-morbidities during follow-up and bone mineral density

Description

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.

Time Frame

At baseline, at end of gonadotoxic chemotherapy (EoT; corresponding to Baseline+2-11 months) and 12 months and 5 years after EoT

Title

Disease-specific oncologic outcomes: disease-free survival

Description

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.

Time Frame

At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.

Title

Disease-specific oncologic outcomes: Recurrence rate

Description

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.

Time Frame

At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.

Title

Disease-specific oncologic outcomes: overall survival

Description

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.

Time Frame

At 12 months, 2 years, 3 years, 4 years and 5 years after EoT.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

42 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kenny Rodriguez Wallberg, MD, PhD

Phone

+46 858580000

kenny.rodriguez-wallberg@ki.se

First Name & Middle Initial & Last Name or Official Title & Degree

Hanna Nilsson, PhD

hanna.nilsson@ki.se

Facility Information:

Facility Name

Center for Pediatric Cancer, Queen Silvia Hospital for Children and Youth

City

Göteborg

Country

Sweden

Facility Name

Center for Pediatric Oncology, Akademiska Hospital

City

Göteborg

Country

Sweden

Facility Name

Department of Oncology, Sahlgrenska University Hospital

City

Göteborg

Country

Sweden

Facility Name

Department of Hematology, Skåne University Hospital

City

Lund

Country

Sweden

Facility Name

Department of Oncology, Skåne University Hospital

City

Lund

Country

Sweden

Facility Name

Department of Pediatric Oncology, Skåne University Hospital

City

Lund

Country

Sweden

Facility Name

Karolinska Univeristy Hospital, Breast Centre

City

Stockholm

ZIP/Postal Code

17176

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Theo Foukakis, MD, PhD

theo.foukakis@ki.se

Facility Name

Department of Hematology and coagulation, Sahlgrenska University Hospital

City

Stockholm

Country

Sweden

Facility Name

Department of Hematology, Capio ST. Göran Hospital

City

Stockholm

Country

Sweden

Facility Name

Department of Internal Medicine, Södersjukhuset

City

Stockholm

Country

Sweden

Facility Name

Department of Oncology, Capio ST. Göran Hospital

City

Stockholm

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Erika Isaksson Friman

Facility Name

Department of Oncology, Södersjukhuset

City

Stockholm

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christina Linder-Stragliotto

Facility Name

Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet

City

Stockholm

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Per Ljungman

Facility Name

Karolinska University Hospital, Hematology

City

Stockholm

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sara Harrysson, MD, PhD

sara.harrysson@regionstockholm.se

Facility Name

Karolinska University Hospital, High Specialised Pediatric Medicine

City

Stockholm

Country

Sweden

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Johan Malmros, MD, PhD

johan.malmros@ki.se

Facility Name

Department of Oncology, Norrlands University Hospital

City

Umeå

Country

Sweden

Facility Name

Department of Oncology, Örebro University Hospital

City

Örebro

Country

Sweden

12. IPD Sharing Statement

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Use of GnRHa During Chemotherapy for Fertility Protection

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