EDEN : Etude de désescalade thérapeutique et d'évaluation du marqueur miRNA M371 pour les séminomes de stade IIa/IIb < 3 cm

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Leon Berard

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 May 2023 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-514636-25-00

EudraCT number

2021-006758-30

ClinicalTrials.gov

NCT05529251

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Therapy

To evaluate the efficacy of de-escalated therapy [1 cycle of EP (Etoposide cisPlatine) followed, in case of negative FDG-PET at week 3, by either 1 cycle of carboplatin AUC 7 or a boost of radiotherapy (RT) on lymph nodes] on the time to first relapse in patients with stage IIa/IIb < 3 cm seminoma.

Secondary objectives 5

1. The serum level of miRNA-M371 as potential biomarker of response,
2. The association between FDG-PET results and miRNA M371 rate,
3. The overall survival (OS)
4. The quality of life (QoL) (QLQ-C30 questionnaire),
5. The safety (NTI-CTCAE v5.0).

Conditions and MedDRA coding

Stage IIa/IIb < 3 cm seminoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. I1. Age ≥ 18 years on the day of signing informed consent.
2. I2. Primary testicular seminomatous germ cell tumor.
3. I3. Stage IIa/IIb N < 3 cm in largest diameter seminoma, histologically proved after orchiectomy.
4. I4. Confirmation of a progressive disease (positive FDG-PET or increase of lymph nodes size by two successive CT scan).
5. I5. Good prognosis according to IGCCCG and LDH < 2.5 x ULN
6. I6. Normal AFP before and after orchiectomy
7. I7. No prior treatment with radiotherapy or chemotherapy
8. I8. ECOG PS ≤ 2
9. I9. Adequate bone-marrow, hepatic, and renal functions with: - Neutrophils ≥ 1.5 x 109 /l, platelets ≥ 100 x 109 /l, - AST (SGOT) and ALT (SGPT) ≤ 1,5 x ULN, - Serum creatinine < 140 µmol/l OR calculated clearance > 60 ml/min (using either Cockcroft-Gault formula or MDRD for > 65 years old), - Total bilirubin ≤ ULN (if >ULN, direct bilirubin ≤ ULN).
10. I10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
11. I11. Accepting to use effective contraceptive measures or abstain from heterosexual activity, for the course of the study and through 12 months after the last dose of chemotherapy or being surgically sterile. All patients should seek advice regarding cryoconservation of sperm prior treatment initiation because of the possibility of infertility. Refer to Appendix 1 for approved methods of contraception.
12. I12. Affiliation to a health insurance
13. I13. Signed and dated informed consent.

Exclusion criteria 8

1. NI1. Extra-retroperitoneal metastasis on CT-scan.
2. NI2. Infection by HIV, or active infection with the Hepatitis B or C virus
3. NI3. History, within 2 years, of cancer other than seminoma, except for treated skin cancer (basal cell).
4. NI4. Uncontrolled or severe cardiovascular pathology.
5. NI5. Uncontrolled or severe hepatic pathology.
6. NI6. Patient deprived of liberty or requiring tutorship or curatorship
7. NI7. Psychological, physical, sociological, or geographical conditions that would limit compliance with study protocol requirements (at the investigator’s discretion).
8. NI8. Participation to another clinical trial, except for supportive care trials.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the progression-free rate at 36 months (PFR-36m) defined as the proportion of patients with a complete response (CR), a partial response (PR) or a stable disease (SD) at 36 months according to RECIST v1.1. Prevalence of events (relapse or death) is expected to be low

Secondary endpoints 5

1. - Association between serum level of miRNA-M371 (MiRNA-M371 expression rate measured before the introduction of chemotherapy, before the second cycle of chemotherapy (EP or carboplatin) or before the beginning of radiotherapy and at the end of treatment) and response to treatment (according to RECIST v1.1)
2. - Correlation between serum level of miRNA-M371 and FDG-PET results (complete metabolic response),
3. - OS, defined as the time from the date of inclusion to the date of death from any cause. Any patient whose death is not known at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive
4. - QoL, assessed using the EORTC QLQ-C30 (baseline, at the end of treatment visit).
5. - Safety profile, determined using the NCI-CTC AE grading scale version 5. Adverse events will be described by their intensity and severity.

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Leon Berard

Sponsor organisation

Centre Leon Berard

Address

28 Rue Laennec

City

Lyon

Postcode

69008

Country

France

Scientific contact point

Organisation

Centre Leon Berard

Contact name

Dr Aude FLECHON

Public contact point

Organisation

Centre Leon Berard

Contact name

Clinical Operations Manager

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 9 files

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

Application history

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