Seminoma Clinical Trial
— EDENOfficial title:
Prospective Therapeutic De-escalation and miRNA-M371 Biomarker Evaluation Phase II Study for Stage IIa/IIb < 3 cm Seminomas
Phase II, multicenter, prospective, randomized, non-comparative, de-escalation study. Patients with stage IIa/IIb < 3 cm seminoma histologically proved after orchiectomy will be included in the study and will receive 1 cycle of Etoposide Cisplatine (EP) chemotherapy. Patients with negative week-3 PET-scan after the EP cycle, will be randomized (1:1 ratio, stratification according to the disease stage (stage IIa versus IIb seminoma)) to receive either radiotherapy (RT) boost on lymph nodes or 1 cycle of carboplatin AUC7 chemotherapy. Patients with positive week-3 PET-scan will received 3 additional cycles of EP chemotherapy. In parallel, eligible patients scheduled to receive standard lombo-aortic RT will be registered in an observational cohort.
Status | Recruiting |
Enrollment | 90 |
Est. completion date | September 6, 2030 |
Est. primary completion date | September 6, 2025 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility | Inclusion criteria : 1. Age = 18 years on the day of signing informed consent. 2. Primary testicular seminomatous germ cell tumor. 3. Stage IIa/IIb < 3 cm in largest diameter seminoma, histologically proved after orchiectomy. 4. Confirmation of a progressive disease (positive PET scan or increase of lymph nodes size by two successive CT scan). 5. Good prognosis according to IGCCCG and LDH < 2.5 x Upper Limit of Normal (ULN). 6. Normal alpha-fetoprotein (AFP) before and after orchiectomy. 7. No prior treatment with radiotherapy or chemotherapy. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2. 9. Adequate bone-marrow, hepatic, and renal functions with: - Neutrophils = 1.5 x Giga/l, platelets = 100 x Giga/l, - Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 1,5 x ULN, - Serum creatinine < 140 µmol/l OR calculated clearance > 60 ml/min (using either Cockcroft-Gault formula or Modification of Diet in Renal Disease (MDRD) for > 65 years old), - Direct and total bilirubin = ULN. 10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 11. 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 12. Affiliation to a health insurance. 13. Signed and dated informed consent. Non-exclusion criteria : 1. Extra-retroperitoneal metastasis on Computed tomography scan (CT scan). 2. Infection by Human Immunodeficiency Virus (HIV), or active infection with the Hepatitis B or C virus. 3. History, within 2 years, of cancer other than seminoma, except for treated skin cancer (basal cell). 4. Uncontrolled or severe cardiovascular pathology. 5. Uncontrolled or severe hepatic pathology. 6. Patient deprived of liberty or requiring tutorship or curatorship. 7. Psychological, physical, sociological, or geographical conditions that would limit compliance with study protocol requirements (at the investigator's discretion). 8. Participation to another clinical trial, except for supportive care trials. |
Country | Name | City | State |
---|---|---|---|
France | CHU Besançon | Besançon | |
France | CHU Bordeaux | Bordeaux | |
France | Centre François Baclesse | Caen | |
France | Centre Jean Perrin | Clermont-Ferrand | |
France | Centre Oscar Lambret | Lille | |
France | CHU de Limoges | Limoges | |
France | Centre Leon Bérard | Lyon | |
France | Institut Paoli Calmettes | Marseille | |
France | Centre Antoine Lacassagne | Nice | |
France | Hôpital Saint Louis | Paris | |
France | ICO René Gauducheau | Saint-Herblain | |
France | Hôpital Foch | Suresnes | |
France | Institut Universitaire de Cancer de Toulouse (IUCT-O) | Toulouse | |
France | Institut de Cancérologie de Lorraine | Vandœuvre-lès-Nancy | |
France | Institut Gustave Roussy | Villejuif |
Lead Sponsor | Collaborator |
---|---|
Centre Leon Berard |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PFR-36M | Progression-free rate at 36 months
The PFR-36M is assumed to be a random variable following a binomial distribution Bin (n, p) where n is the sample size and p is the true underlying PFR-36M. Conclusions and inferences will be conducted on p. The prior distribution of p (representing the knowledge of the progression-free rate probability prior to observing the data) will be pre-specified. In the absence of a strong idea about the PFR-36M to be observed, a non-informative prior distribution Beta (1,1) will be considered. Pr[PFR-36M = 80%] will be expressed in each arm, associated with its 95% credibility interval. A treatment arm will be considered a positive sign for efficacy of de-escalation if there is a high probability that PFR-36M will be higher or equal to 80%: Pr[PFR-36M = 80%] = 90%. It means that if most of the distribution (90% of it) falls to the right hand side of 80%, it indicates that it is very likely that the effect is at least 80% |
Up to 36 months after inclusion | |
Secondary | miRNA-M371 | Serum level of miRNA-M371 as a potential biomarker of response. Association between serum level of miRNA M371 and response to treatments (according to RECIST v1.1) will be evaluated using a non-parametric Wilcoxon Mann and Whitney test and describe with boxplots. | Up to 5 years | |
Secondary | Association of PET scan results and miRNA-M371 rate | Correlation between serum level of miRNA M371 and FDG-PET results (metabolic response) will be evaluated using the Kendall rank correlation and describe graphically. | Up to 5 years | |
Secondary | Overall survival (OS) | The Overall Survival will be defined as the time from date of inclusion to the date of death, from any cause. 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.
The Kaplan-Meier (KM) approach will be used to estimate median OS. Median OS as well as Survival rates at specific timepoints will be presented together with their 95% confidence interval (CI). |
Up to 3 years | |
Secondary | Quality of life (QoL) | The QoL will be assessed using the EORTC QLQ-C30 questionnaire. | Up to 20 months | |
Secondary | Tolerance to treatment | The tolerance to each treatment will be described mainly on the frequency of adverse events (AEs) and their intensity and severity determined using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 5. Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment.
AEs will be described and coded, in total and per System Organ Class and Preferred Term with Medical Dictionary for Regulatory Activities (MedDRA) coding |
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