Background: Multiple relapsed/refractory GCTs patients have extremely poor prognosis, therefore, new treatment strategies are warranted. Previously, we showed, that cisplatin resistant testicular GCTs overexpress aldehyde-dehydrogenase (ALDH) isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity in vitro as well as in animal model. This study aimed to determine the efficacy and toxicity of ALDH inhibitor disulfiram in combination with cisplatin in patients with multiple relapsed/refractory germ cell cancer. Methods: Twelve patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from May 2019 to September 2021. All patients were pretreated with at least 2 cisplatin-based therapies (median 4, range 2 – 7); 6 tumors (50.0%) were absolutely refractory to cisplatin and 9 patients (75.0%) had visceral non-pulmonary metastases. Disulfiram was administered at a dose of 400 mg daily until progression or unacceptable toxicity, cisplatin was administered at dose 50 mg/m² day 1 and 2, every 3 weeks. Twelve evaluable patients had to be enrolled into the first cohort, and if 0 of 12 patients had treatment response, the study was to be terminated. The results of the first stage of the trial are presented in the this report. Results: Median age was 36 years (range: 29 – 48 years). Median number of treatment cycles was 2 (range 1 – 6). During a median follow-up period of 3.1 months (range: 1.3 – 13.9), all (100%) patients experienced disease progression and died. None of patients achieved objective response to treatment, therefore the study was terminated in first stage. Median progression-free survival (PFS) was 1.4 months, 95% CI (0.7 – 1.5 months), and median overall survival (OS) was 2.9 months 95% CI (1.5 – 4.7 months). Disease stabilization for at least 6 months was observed in 2 (16.7%) patients. Treatment was well tolerated, however, 5 (41.7%) of patients experienced grade 3/4 fatigue, 4 (33.3%) thrombocytopenia, 3 (25.0%) anemia, while 2 (16.7%) experienced neutropenia, nausea and infection. Conclusions: This study failed to achieve its primary end point and our data suggest limited efficacy of disulfiram in restoring sensitivity to cisplatin in multiple relapsed/refractory germ cell tumors. Clinical trial information: NCT03950830.