E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast Cancer Acute Leukemia Lymphomas (Hodgkin and non-Hodgkin) Sarcomas (Osteo, Soft tissue and Ewing)
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Bröstcancer, Akut Leukemi, Lymfom (Hodgkin och non-Hodgkin), Sarkom (Ben, Mjukvävnad och Ewing)
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E.1.1.1 | Medical condition in easily understood language |
Breast Cancer Blood Cancer Cancer in lymphnodes Cancer in bones |
Bröstcancer, Blodcancer, Cancer i lymfkörtlar, Cancer i skelett
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To estimate the changes in ovarian reserve following chemotherapy for treatment of cancer with or without Gonadotropin-Releasing Hormone agonist (GnRHa) by determination of the Anti-Müllerian Hormone (AMH) at 12 months after end of gonadotoxic chemotherapy (EoT) in women with breast cancer. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objective: 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 Secondary objectives: To estimate the changes in ovarian reserve with or without GnRHa by determination of the antral follicle counts in women with breast cancer, acute leukemias, lymphomas and sarcomas To estimate the changes in ovarian reserve with or without GnRHa by longitudinal observation of AMH levels in women with breast cancer, acute leukemias, lymphomas and sarcomas To compare the proportion of females with or without GnRHa that develop ovarian insufficiency by determination of FSH, inhibin and estradiol To investigate 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, etc. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed informed consent • Age 14-42 years at cancer diagnosis • 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 • Confirmed menarche • ECOG performance status 0-1 • Adequate bone marrow, renal, hepatic and cardiac functions and absence of other uncontrolled medical or psychiatric disorders
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E.4 | Principal exclusion criteria |
Subjects must not be included in the study if any of the following criteria are met: • Ongoing treatment with GnRHa at baseline • 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 refractory thrombocytopenia in subjects with acute leukemias • Known or suspected allergy against Pamorelin • Direct radiation of the gonads previous or planned (Total body irradiation allowed) • Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation |
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E.5 End points |
E.5.1 | Primary end point(s) |
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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At follow-up 12 months after EoT |
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E.5.2 | Secondary end point(s) |
Key secondary endpoint: 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 Secondary endpoints: • Comparison of antral follicle counts 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • Comparison of blood flow to the ovarian artery at baseline (right and left Doppler flow PI, RI) 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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 • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • Comparison of health-related quality of life, 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas • 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: o In women with breast cancer o In women with acute leukemias, lymphomas and sarcomas |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary objective: At follow-up 12 months after EoT
Secondary obejectives: EoT, 6, 12 months after EoT and continuously during follow-up years 2, 3, 4, 5 after EoT |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |