A Phase 2 interventional study of Disulfiram in Germ Cell Tumor, sponsored by National Cancer Institute, Slovakia. Completed at 1 site in Slovakia. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-04.
Sponsored by National Cancer Institute, Slovakia · Phase 2, Interventional, and Treatment
Non-randomized, open-label, single center trial to assess efficacy (as measured by overall response rate (ORR) by RECIST 1.1 of disulfiram and cisplatin in patients with multiple relapsed/refractory germ cell tumors (GCTs).
Germ-cell tumours (GCTs) are extraordinarily chemosensitive and resemble the clinical and biological characteristics of a model for the cure of cancer. Nonetheless, a small proportion of patients do not have a durable complete remission (CR) with initial chemotherapy. Only 20-40% of them will be cured with the use of platinum-containing standard-dose or high-dose salvage chemotherapy with autologous stem cell transplantation (ASCT). Patients who fail to be cured after second-line salvage therapy have an extremely poor prognosis and long term survival had been documented in \<5%. Paclitaxel plus ifosfamide and cisplatin is considered as a standard salvage chemotherapy in relapsed good prognosis GCTs, however, up to 40% of favourable prognosis patients failed to achieve durable response to this combination, and therefore new treatment strategies are warranted.
Previously, it was showed that cisplatin resistant TGCTs overexpress ALDH isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity. Cisplatin-resistant TGCTs exhibited increased sensitivity to ALDH inhibitor disulfiram in vitro. Although Disulfiram (Antabuse) is an approved drug to support the treatment of chronic alcoholism, it may serve as an antitumor agent suitable for the drug repurposing in combination therapy in order to inhibit ALDH activity thus overcoming a cisplatin resistance in refractory TGCTs. Indeed, disulfiram in combination with cisplatin very efficiently eradicated platinum-resistant NTERA-2 model spheroids and significantly inhibited xenograft growth in vivo in our experimental system.
Based on aforementioned data, investigators suggest that there is strong rationale to inhibit ALDH in TGCT. Investigators hypothesize that inactivation of ALDH by disulfiram recover cisplatin sensitivity in patients with progressing or relapsing germ cell cancer.
291 studies on the registry are indexed under Neoplasms, Germ Cell and Embryonal; 51 are open to participants now.
This study's enrollment of 12 is below the median of 37 across 211 interventional studies indexed under Neoplasms, Germ Cell and Embryonal.
Browse Neoplasms, Germ Cell and Embryonal studies →National Cancer Institute, Slovakia is the lead sponsor of 7 studies on the registry; 2 are open to participants now.
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Exclusion Criteria:
Cisplatin 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily, continuously
Drug: Disulfiram
Disulfiram 400mg daily, continuously
Also known as: Antabus
Overall response rate
Overall response rate by RECIST 1.1
Time frame: 24 months
Progression-free survival
Progression-free survival
Time frame: 24 months
Overall survival
Overall survival
Time frame: 24 months
Plan to share: No
No publications or documents are linked to this record.
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
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Neoplasms, Germ Cell and Embryonal→
National Cancer Institute, Slovakia