Randomized phase II trial of maintenance oral etoposide versus observation following high-dose chemotherapy and peripheral blood stem cell transplant in relapsed non-seminomatous germ cell tumors.

Abstract

TPS625 Background: High-dose chemotherapy (HDCT) followed by peripheral-blood stem-cell transplant (PBSCT) remains an effective salvage approach for patients with relapsed germ-cell tumors (GCT). When administered in the second-line setting, this strategy leads to durable remissions in roughly 60% of those with relapsed non-seminoma (NSGCT). Prior retrospective evidence suggests that maintenance therapy with oral etoposide after HDCT improves progression-free survival (PFS) and overall survival (OS). We intend to evaluate the efficacy and safety of maintenance daily oral etoposide after HDCT+PBSCT in patients with relapsed non-seminoma. Methods: This is a randomized, open-label, phase II clinical trial evaluating oral etoposide maintenance therapy after completion of HDCT and PBSCT. Eligible patients are adults with metastatic NSGCT who have experienced progression after first-line cisplatin-based chemotherapy. All participants will complete two tandem cycles of HDCT using the Indiana carboplatin/etoposide protocol. At randomization, patients must demonstrate normal or decreasing serum tumor markers (AFP and/or hCG), no evidence of radiographic progression, and recovery from treatment-related toxicities to grade ≤2. Randomization will occur within 16 weeks after the second HDCT cycle. Patients with primary mediastinal non-seminoma are eligible. Patients with relapsed pure seminoma are excluded. Participants will be randomized 1:1 to receive either maintenance oral etoposide or observation, stratified by platinum-refractory status (progression within four weeks of first-line therapy). The intervention arm will receive oral etoposide at 50 mg daily for 21 days of each 28-day cycle, for a total of three cycles. Weekly labs including CBC with differential will are planned for hematological toxicity monitoring. The primary endpoint is 12-month progression-free survival (PFS), while secondary endpoints include toxicity and 12-month overall survival (OS). Exploratory analyses will assess circulating microRNA-371 levels at screening and their association with relapse risk. As of October 10, 2025, 38 patients have been enrolled out of the planned 64. Fourteen patients declined randomization, and ten were found ineligible after screening. Accrual and follow-up are ongoing. Clinical trial information: NCT04804007 .