Condition or disease | Intervention/treatment | Phase |
---|---|---|
Germ Cell Tumor | Drug: Disulfiram | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 20 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Non-randomized, open-label, single center trial to assess efficacy (as measured by overall response rate of disulfiram and cisplatin in patients with multiple relapsed/refractory germ cell tumors (GCTs). |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase II Study of Disulfiram and Cisplatin in Refractory TGCTs. |
Actual Study Start Date : | May 14, 2019 |
Estimated Primary Completion Date : | December 31, 2021 |
Estimated Study Completion Date : | December 31, 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Treatment arm
Cisplatin 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily, continuously
|
Drug: Disulfiram
Disulfiram 400mg daily, continuously
Other Name: Antabus
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Michal Mego, Prof | +421-2-59378352 | michal.mego@nou.sk | |
Contact: Daniela Svetlovska, Dr | +421-2-59378592 | daniela.svetlovska@nou.sk |
Slovakia | |
National Cancer Institute | Recruiting |
Bratislava, Slovakia, 83310 | |
Contact: Michal Mego, Assoc. Prof +421259378 ext 366 michal.mego@nou.sk | |
Contact: Jozef Mardiak, Prof +421259378 ext 108 jozef.mardiak@nou.sk | |
Principal Investigator: Jozef Mardiak, Prof | |
Principal Investigator: Michal Mego, Assoc. Prof |
Principal Investigator: | Michal Mego, Prof | National Cancer Institute, Slovakia |
Tracking Information | |||||||||
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First Submitted Date ICMJE | May 12, 2019 | ||||||||
First Posted Date ICMJE | May 15, 2019 | ||||||||
Last Update Posted Date | August 6, 2020 | ||||||||
Actual Study Start Date ICMJE | May 14, 2019 | ||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Overall response rate [ Time Frame: 24 months ] Overall response rate by RECIST 1.1
|
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Disulfiram and Cisplatin in Refractory TGCTs. | ||||||||
Official Title ICMJE | Phase II Study of Disulfiram and Cisplatin in Refractory TGCTs. | ||||||||
Brief 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). | ||||||||
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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Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: Non-randomized, open-label, single center trial to assess efficacy (as measured by overall response rate of disulfiram and cisplatin in patients with multiple relapsed/refractory germ cell tumors (GCTs). Masking: None (Open Label)Primary Purpose: Treatment |
||||||||
Condition ICMJE | Germ Cell Tumor | ||||||||
Intervention ICMJE | Drug: Disulfiram
Disulfiram 400mg daily, continuously
Other Name: Antabus
|
||||||||
Study Arms ICMJE | Experimental: Treatment arm
Cisplatin 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily, continuously
Intervention: Drug: Disulfiram
|
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
20 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 31, 2022 | ||||||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
|
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Sex/Gender ICMJE |
|
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
|
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Listed Location Countries ICMJE | Slovakia | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03950830 | ||||||||
Other Study ID Numbers ICMJE | GCT-SK-006 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | National Cancer Institute, Slovakia | ||||||||
Study Sponsor ICMJE | National Cancer Institute, Slovakia | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute, Slovakia | ||||||||
Verification Date | July 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |