Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03950830
Other study ID # GCT-SK-006
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date May 14, 2019
Est. completion date January 31, 2022

Study information

Verified date October 2023
Source National Cancer Institute, Slovakia
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date January 31, 2022
Est. primary completion date September 30, 2021
Accepts healthy volunteers No
Gender Male
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Disulfiram
Disulfiram 400mg daily, continuously

Locations

Country Name City State
Slovakia National Cancer Institute Bratislava

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute, Slovakia

Country where clinical trial is conducted

Slovakia, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall response rate Overall response rate by RECIST 1.1 24 months
Secondary Progression-free survival Progression-free survival 24 months
Secondary Overall survival Overall survival 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT06133543 - Robot-assisted ICG-guided Sentinel Node Biopsy in Testicular Cancer N/A
Terminated NCT00369291 - CpG 7909 in Treating Patients Who Have Undergone Autologous Stem Cell Transplant Phase 1
Terminated NCT00198172 - Phase II Study of Cisplatin Plus Epirubicin Salvage Chemo in Refractory Germ Cell Tumors Phase 2
Recruiting NCT05874063 - Thromboprophylaxis in Good and Intermediate Prognosis Advanced Germ Cell Tumors Phase 3
Completed NCT03194906 - Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors Phase 2
Completed NCT01466231 - Everolimus in Refractory Testicular Germ Cell Cancer Phase 2
Recruiting NCT04791228 - A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors Phase 2
Active, not recruiting NCT03418844 - Living After a Rare Cancer of the Ovary: Chronic Fatigue, Quality of Life and Late Effects of Chemotherapy N/A
Recruiting NCT05889585 - Morbidity, Long-term Side Effects and Quality of Life in Germ-cell Tumor Long Survivors Treated With High-dose Chemotherapy and Autologous Stem Cell Transplant
Recruiting NCT05394675 - A Study of DS-9606a in Patients With Advanced Solid Tumors Phase 1
Recruiting NCT03067181 - Active Surveillance, Bleomycin, Etoposide, Carboplatin or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors Phase 3
Withdrawn NCT03960151 - Rolapitant Plus Olanzapine in Multiday Cisplatin Chemotherapy Phase 2
Active, not recruiting NCT03158064 - Evaluating Immune Therapy, Duravalumab (MEDI4736) With Tremelimumab for Relapsed/Refractory Germ Cell Tumors Phase 2
Recruiting NCT00898755 - Collecting and Storing Tissue From Young Patients With Cancer
Recruiting NCT04804007 - Maintenance Oral Etoposide or Observation Following High-dose Chemo for GCT Phase 2
Terminated NCT02988843 - Study of Brentuximab Vedotin And Bevacizumab In Refractory CD-30 Positive Germ Cell Tumors Phase 2
Recruiting NCT05259605 - Observational Study for Assessing Treatment and Outcome of Patients With Primary Brain Tumours Using cIMPACT-NOW and 2021 WHO Classification
Active, not recruiting NCT03638167 - EGFR806-specific CAR T Cell Locoregional Immunotherapy for EGFR-positive Recurrent or Refractory Pediatric CNS Tumors Phase 1
Recruiting NCT04308330 - Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies Phase 1
Recruiting NCT06418789 - High-dose Chemotherapy as Second-line Drug Therapy for Relapsed Germ Cell Tumors Phase 2