NCT05529251

De-escalation Study for Stage IIa/IIb < 3 cm Seminoma

Prospective Therapeutic De-escalation and miRNA-M371 Biomarker Evaluation Phase II Study for Stage IIa/IIb < 3 cm Seminomas

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Centre Leon Berard · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Stage II seminoma is defined by the presence of retroperitoneal lymph node metastases. It concerns approximately 15% of patients with seminoma. The standard treatment for patients with stage IIa/b seminoma, after orchiectomy, is extended lumbo-aortic/ipsilateral iliac radiotherapy (RT). Performing chemotherapy (CT) with 3 courses of Bleomycin-Etoposide-Cisplatin (BEP) or 4 courses of Etoposide-Cisplatin (EP) is an alternative. The optimal treatment choice remains controversial. Both treatment modalities are associated with excellent efficacy but also acute and late toxicities. European Society of Medical Oncology (ESMO) guidelines recommended in equal measure CT and RT for stage IIa. A recent systematic review concluded that RT and cisplatin-based combination CT are equally effective in clinical stage IIa/IIb seminoma, with a trend in favor of chemotherapy in stage IIb because of lower relapse rate. However, due to the rarity of stage II seminoma, a sufficiently powered randomized trial comparing radiotherapy with chemotherapy is unlikely to be completed. De-escalation strategies are required to minimize acute and long-term toxicities while maintaining efficacy. De-escalated treatment for seminoma patients with stage IIb/IIC/III and good prognosis according to International Germ Cell Cancer Collaborative Group (IGCCCG), based on negative PET after 2 cycles of EP chemotherapy, is feasible and safe according to SEMITEP results (cohort 2). In case of negative PET, 1 additional cycle of CT with carboplatin AUC7 was administered. Furthermore, serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage, primary tumor size and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers (hCGt, LDH). However, further evaluations are needed before modifying clinical practices. We propose to conduct a multicenter, prospective, randomized, non-comparative, de-escalation phase II study in patients with stage IIa/IIb seminoma \< 3 cm, evaluating: * a more de-escalated CT treatment: 1 cycle of EP followed, in case of negative PET, by either a boost of RT on lymph node or 1 cycle of carboplatin AUC7 * the biomarker miRNA-M371 in therapeutic decision and correlation with PET. In parallel, eligible patients scheduled to receive standard lombo-aortic RT will be registered in an observational cohort.

Conditions

• Seminoma
• Stage II

Interventions

Type	Name	Description
RADIATION	Radiotherapy boost	Radiotherapy 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
DRUG	Carboplatin AUC7	Carboplatin at dose (mg) = AUC7 (mg/ml x min) x (DFG ml/min + 25)
DRUG	3 cycles of EP	3 Cycles of EP chemotherapy, administred every 3 weeks following standard practice

Timeline

• Start date: 2022-09-06
• Primary completion: 2025-09-06
• Completion: 2030-09-06
• First posted: 2022-09-07
• Last updated: 2024-01-25

Locations

15 sites across 1 country: France