Clinical trial • Phase III • Oncology|Haematology

triptorelin for Breast cancer|Acute leukemia|Hodgkin lymphoma|Non-Hodgkin lymphoma|Osteosarcoma|Soft tissue sarcoma|Ewing sarcoma

Phase III trial of triptorelin for Breast cancer|Acute leukemia|Hodgkin lymphoma|Non-Hodgkin lymphoma|Osteosarcoma|Soft tissue sarcoma|Ewing sarcoma.

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
Breast cancer|Acute leukemia|Hodgkin lymphoma|Non-Hodgkin lymphoma|Osteosarcoma|Soft tissue sarcoma|Ewing sarcoma
Trial Stage
Phase III
Drug Modality
Peptide/protein/enzyme|Other
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
14-10-2024
First CTIS Authorization Date
25-10-2024

Trial design

Randomised, placebo: 0.9% sodium chloride solution (placebo syringes need to be covered with aluminium foil by the unblinded research nurse to maintain the study blind). test/active: pamorelin (triptorelin) 3.75 mg prolonged-release suspension for injection, intramuscular; pamorelin (triptorelin) 11.25 mg prolonged-release suspension for injection, intramuscular. schedule not specified in the available data.-controlled Phase III trial across 21 sites in Sweden.

Randomised
Yes
Comparator
Placebo: 0.9% Sodium Chloride solution (placebo syringes need to be covered with aluminium foil by the unblinded research nurse to maintain the study blind). Test/active: Pamorelin (triptorelin) 3.75 mg prolonged-release suspension for injection, intramuscular; Pamorelin (triptorelin) 11.25 mg prolonged-release suspension for injection, intramuscular. Schedule not specified in the available data.
Target Sample Size
500

Eligibility

Recruits 500 paediatric patients.

Pregnancy Exclusion
Pregnancy or breastfeeding at time of start of chemotherapy
Vulnerable Population
Vulnerable population selected. Trial includes adolescents aged 14-17. 'Signed informed consent' is required. Subject information and informed consent form documents present for adults and for 14-17 year olds ('L1_SIS and ICF_adults_v3_0_20220516' and 'L1_SIS and ICF_14-17 yr_v3_0_20220516').

Inclusion criteria

  • {"criterion_text":"- Signed informed consent\n- Age 14-42 years at cancer diagnosis\n- 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\n- Confirmed menarche\n- ECOG performance status 0-1\n- Adequate bone marrow, renal, hepatic and cardiac functions and absence of other uncontrolled medical or psychiatric disorders"}

Exclusion criteria

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

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Determination of Anti-Müllerian Hormone (AMH) at 12 months after end of gonadotoxic treatment (EoT) compared to AMH at EoT; comparison between GnRHa and placebo groups."}

Secondary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Determination of AMH at 12 months after EoT compared to AMH at EoT; comparison between GnRHa and placebo groups in acute leukemias, lymphomas and sarcomas."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Antral follicle count (AFC) measured by ultrasound at EoT, 6 and 12 months after EoT and then annually years 2-5; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Longitudinal determination of AMH at 6 months and annually years 2-5 after EoT; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measurement of FSH, inhibin and estradiol at specified timepoints (EoT, 6, 12 months, years 2-5); comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Doppler ultrasound measurement of ovarian artery blood flow (PI, RI) at baseline, EoT, 6, 12 months and annually years 2-5; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessment of amenorrhea (absence of menstruation) at EoT, 6, 12 months and annually years 2-5; proportion comparison between groups."}
  • {"endpoint_text":"- 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","definition_or_measurement_approach":"Longitudinal observation of AMH, FSH, inhibin and estradiol at standardized timepoints to evaluate impact of BMI, contraceptive use and adjuvant endocrine therapy."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Capture of pregnancy wish, attempts and outcomes at EoT, 6, 12 months and annually years 2-5; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessment of health-related quality of life, sexuality and reproductive health at specified timepoints; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measurement of bone mineral density at baseline, EoT, 12 months and year 5; comparison between groups."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Assessment of recurrence rate, overall survival and disease-free survival at 12 months and annually years 2-5; comparison between groups."}

Recruitment

Planned Sample Size
500
Recruitment Window Months
96
Consent Approach
Signed informed consent required. Subject information and informed consent forms available for adults and for 14-17 year olds (documents: 'L1_SIS and ICF_adults_v3_0_20220516' and 'L1_SIS and ICF_14-17 yr_v3_0_20220516'). No languages or additional consent/assent details provided in the available data.

Geography

Total Number Of Sites
21
Total Number Of Participants
500

Sweden

Earliest CTIS Part Ii Submission Date
12-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
13
Number Of Sites
21
Number Of Participants
500

Sites

Site Name
Region Oerebro Laen
Department Name
Universitetssjukhuset Örebro, Oncology
Contact Person Name
Antonios Valachis
Contact Person Email
antonios.valachis@oru.se
Site Name
Soedersjukhuset AB
Department Name
Oncology
Contact Person Name
Anna Von Wachenfeldt Väppling
Site Name
Karolinska University Hospital
Department Name
Breast, Endocrine Tumors and Sarcoma
Contact Person Name
Tobias Lekberg
Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Oncology
Contact Person Name
Barbro Linderholm
Site Name
Capio S:t Goerans Sjukhus AB
Department Name
Oncology
Contact Person Name
Eneida Lindfors
Site Name
Karolinska University Hospital
Department Name
Gynecology and Reproductive Medicine
Contact Person Name
Kenny Rodriguez-Wallberg
Site Name
Uppsala University Hospital
Department Name
Center for Pediatric Oncology, Akademiska Sjukhuset
Contact Person Name
Per Frisk
Contact Person Email
per.frisk@akademiska.se
Site Name
Region Oerebro Laen
Department Name
Hematology
Contact Person Name
Bertil Uggla
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Pediatric Oncology
Contact Person Name
Helena Mörse
Contact Person Email
helena.morse@med.lu.se
Site Name
Uppsala University Hospital
Department Name
Reproduction Center
Contact Person Name
Stavros Illiadis
Contact Person Email
stavros.illiadis@akademiska.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Reproduction RMC
Contact Person Name
Margareta Kitlinski
Contact Person Email
margareta.kitlinski@skane.se
Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Women´s clinic SU East
Contact Person Name
Randa Akouri
Contact Person Email
randa.akouri@gu.se
Site Name
Region Vaesterbotten
Department Name
Norrlands universitetssjukhus, Daniel Naezéns väg, Oncology
Contact Person Name
Anne Andersson
Contact Person Email
anne.andersson@umu.se
Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Hematology and Coagulation
Contact Person Name
Lovisa Vennström
Contact Person Email
lovisa.vennstrom@vgregion.se
Site Name
Soedersjukhuset AB
Department Name
Internal Medicine, Hematology
Contact Person Name
Mousa Majd
Contact Person Email
mousa.majd@regionstockholm.se
Site Name
Karolinska University Hospital
Department Name
Hematology
Contact Person Name
Sara Harrysson
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Hematology
Contact Person Name
Niklas Loman
Contact Person Email
niklas.loman@med.lu.se
Site Name
Karolinska University Hospital
Department Name
High Specialized Pediatric Medicine
Contact Person Name
Johan Malmros
Site Name
Capio S:t Goerans Sjukhus AB
Department Name
Hematology
Contact Person Name
Barbro Kedinge
Contact Person Email
barbro.kedinge@capiostgoran.se
Site Name
Queen Silvia Childrens Hospital - Sahlgrenska University Hospital - Vaestra Goetalandsregionen
Department Name
Queen Silvia Hospital for Children and Youth Center for Pediatric Cancer
Contact Person Name
Karin Mellgren
Contact Person Email
karin.mellgren@vg.region.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Oncology
Contact Person Name
Mats Jerkerman
Contact Person Email
mats.jerkerman@med.lu.se

Sponsor

Primary sponsor

Full Name
Karolinska University Hospital
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
0.9% Sodium Chloride solution containing 9 mg/ml Sodium Chloride in water for injection. Placebo syringes need to be covered with aluminium foil by the unblinded research nurse to maintain the study blind.
Modality
Other
Investigational Product Name
Pamorelin 3,75 mg pulver och vätska till injektionsvätska, depotsuspension
Active Substance
triptorelin
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAMUSCULAR USE
Route
Intramuscular
Authorisation Status
Authorised
Starting Dose
3.75 mg
Dose Levels
3.75 mg
Maximum Dose
3.75 mg
Investigational Product Name
Pamorelin 11,25 mg pulver och vätska till injektionsvätska, depotsuspension.
Active Substance
triptorelin
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAMUSCULAR USE
Route
Intramuscular
Authorisation Status
Authorised
Starting Dose
11.25 mg
Dose Levels
11.25 mg
Maximum Dose
11.25 mg
Combination Treatment
Yes

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