Disulfiram and Cisplatin in Refractory TGCTs.

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: Male

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute, Slovakia
• Treatments: Cisplatin; Disulfiram

Criteria

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:

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.