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CompletedNCT03950830DISGCTUpdated Oct 4, 2023

Disulfiram and Cisplatin in Refractory TGCTs.

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

Phase
Phase 2
Study type
Interventional
Enrollment
12
Allocation
Not applicable
Ages
18 Years and older
Sex
Male
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Study summary

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).

Read the detailed description

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.

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Conditions studied

  • Germ Cell Tumor
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In context

Neoplasms, Germ Cell and Embryonal

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 →

Lead sponsor

National Cancer Institute, Slovakia is the lead sponsor of 7 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  1. Signed written informed consent .
  2. Men aged 18 years or older.
  3. ECOG performance status: 0-1.
  4. Histologically confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma.
  5. Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer.
  6. Multiple relapsed/refractory GCTs (at least 2 lines of previous chemotherapy and/or patients relapsing after high-dose chemotherapy or for patients non fit enough for high-dose chemotherapy.
  7. Primary mediastinal GCTs in first relapse.
  8. Patient's disease must not be amenable to cure with either surgery or chemotherapy in the opinion of investigator.
  9. RECIST 1.1 Measurable disease.
  10. Adequate hematologic function defined by ANC > 1500/mm3, platelet count > 100 000/mm3 and hemoglobin level > 9g/dl.
  11. Adequate liver function defined by a total bilirubin level \< 1.5 ULN, and ALT, AST \< 3 ULN or \< 5 in case of liver metastases. For subjects with Gilbert's syndrome bilirubin > 1.5 × ULN is allowed if no symptoms of compromised liver function are present.
  12. Adequate renal function: measured or calculated (by Cockcroft formula) creatinine clearance > 50 ml/min. Cockcroft formula: CLcr = [(140-age) x weight (Kg)]/[72 x creat (mg/dl)].
  13. At least 4 weeks must have elapsed since the last radiotherapy and/or chemotherapy before study entry.
  14. At least 4 weeks must have elapsed since the last major surgery.
  15. Complete recovery from prior surgery, and/or reduction of all adverse events from previous systemic therapy or radiotherapy to grade 1.
  16. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Exclusion criteria

Exclusion Criteria:

  1. Patients who do not fit inclusion criteria.
  2. Addiction to alcohol or drugs.
  3. Other prior malignancy except successfully treated nonmelanoma skin cancer .
  4. Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram.
  5. Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives.
  6. Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy.
  7. Female patients.
  8. Patients infected by the Human Immunodeficiency Virus (HIV).
  9. Patients with other severe acute or chronic medical condition, or laboratory abnormality that would impair, in the judgment of investigator, excess risk associated with study treatment, or which, in judgment of the investigator, would make the patient inappropriate for entry into this study.
  10. Inability of oral intake, or drug absorbtion (e.g. malabsorption syndrome).
  11. Hypersensitivity to any compound of the drug.
  12. Sexually active men not using highly effective birth control if their partners are women of child-bearing potential.
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (actual)

Study arms

  • Experimental
    Treatment arm

    Cisplatin 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily, continuously

    Drug: Disulfiram

Interventions

  • DrugDisulfiram

    Disulfiram 400mg daily, continuously

    Also known as: Antabus

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What researchers measure

Primary outcomes

  1. Overall response rate

    Overall response rate by RECIST 1.1

    Time frame: 24 months

Secondary outcomes

  1. Progression-free survival

    Progression-free survival

    Time frame: 24 months

  2. Overall survival

    Overall survival

    Time frame: 24 months

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Study locations

1 site
  • National Cancer Institute
    Bratislava, 83310, Slovakia
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References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 4, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03950830
Lead sponsor
National Cancer Institute, Slovakia
Responsible party
Sponsor
First posted
May 15, 2019
Start date
May 14, 2019
Primary completion
Sep 30, 2021
Completion
Jan 31, 2022
Last update
Oct 4, 2023

Study contacts

Michal Mego, Prof
principal investigator · National Cancer Institute, Slovakia

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

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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