About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years on the day of signing informed consent.
Primary testicular seminomatous germ cell tumor.
Stage IIa/IIb < 3 cm in largest diameter seminoma, histologically proved after orchiectomy.
Confirmation of a progressive disease (positive PET scan or increase of lymph nodes size by two successive CT scan).
Disqualifiers
Extra-retroperitoneal metastasis on Computed tomography scan (CT scan).
Infection by Human Immunodeficiency Virus (HIV), or active infection with the Hepatitis B or C virus.
History, within 2 years, of cancer other than seminoma, except for treated skin cancer (basal cell).
Uncontrolled or severe cardiovascular pathology.
Trial design
Parallel
Treatments tested in this trial
Radiotherapy boost
RadiationRadiotherapy boost 20 to 30 Gy, in daily 2 Gy fractions and 5 fractions per week : * 20 Gy if no more disease is visible (node \< 1 cm in large diameter) * 24 Gy for nodes \<= 2 cm * 30 Gy for nodes \> 2 cm
Carboplatin AUC7
DrugCarboplatin at dose (mg) = AUC7 (mg/ml x min) x (DFG ml/min + 25)
3 cycles of EP
Drug3 Cycles of EP chemotherapy, administred every 3 weeks following standard practice
Treatment groups
Trial outcomes
Primary outcomes
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%
Secondary outcomes
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.
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.
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).
Quality of life (QoL)
The QoL will be assessed using the EORTC QLQ-C30 questionnaire.
Sponsors and contacts
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