Clinical Trial Results:
Phase II study of disulfiram and cisplatin in refractory testicular germ cell cancer.
|
Summary
|
|
EudraCT number |
2019-000558-68 |
Trial protocol |
SK |
Global end of trial date |
13 Dec 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
04 Sep 2022
|
First version publication date |
04 Sep 2022
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
GCTSK006
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03950830 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Národný onkologický ústav
|
||
Sponsor organisation address |
Klenova 1, Bratislava, Slovakia, 833 10
|
||
Public contact |
Oddelenie klinického skúšania, Národný onkologický ústav, 00421 259378592, daniela.svetlovska@nou.sk
|
||
Scientific contact |
Oddelenie klinického skúšania, Národný onkologický ústav, 00421 259378592, daniela.svetlovska@nou.sk
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
03 Nov 2021
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
03 Nov 2021
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
13 Dec 2021
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To determine the efficacy (as measured by overall response rate) (ORR) by RECIST of disulfiram and cisplatin in patients with multiple relapsed/refractory germ cell tumors (GCTs).
|
||
Protection of trial subjects |
All the procedures performed in study involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual paricipants included in the study.
|
||
Background therapy |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment. | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
17 May 2019
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Slovakia: 12
|
||
Worldwide total number of subjects |
12
|
||
EEA total number of subjects |
12
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
12
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
||
|
|||||||
|
Recruitment
|
|||||||
Recruitment details |
Enrollment period started on 14.5.2019 and ended on 3.11.2021. Fisrt patient was enrolled on 17.5.2019, last one on 17.9.2021. Total of 13 patients were screened into the study. One patient did not meet study eligibility criteria, was rescreened and finally 12 subjects were enrolled and receive study treatment. | ||||||
|
Pre-assignment
|
|||||||
Screening details |
Adult men with relapsed/refractory GCTs e.g., 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. Primary mediastinal GCTs in first relapse were eligible too. Patient’s disease could not be amenable to cure with either surgery or chemotherapy. | ||||||
|
Pre-assignment period milestones
|
|||||||
Number of subjects started |
12 | ||||||
Number of subjects completed |
12 | ||||||
|
Period 1
|
|||||||
Period 1 title |
Overall Study ( overall period)
|
||||||
Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
|
||||||
Blinding used |
Not blinded | ||||||
|
Arms
|
|||||||
|
Arm title
|
Cisplatin + Disulfiram | ||||||
Arm description |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Cisplatin
|
||||||
Investigational medicinal product code |
SUB07483MIG
|
||||||
Other name |
Cisplatin Accord, Cisplatin EBEWE
|
||||||
Pharmaceutical forms |
Concentrate for solution for infusion
|
||||||
Routes of administration |
Intravenous use
|
||||||
Dosage and administration details |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment.
Standard emesis prophylaxis will be used (e.g. dexamethason, setron, aprepitant), before cisplatin.
|
||||||
Investigational medicinal product name |
Disulfiram
|
||||||
Investigational medicinal product code |
SUB06326MIG
|
||||||
Other name |
Antabus
|
||||||
Pharmaceutical forms |
Effervescent tablet
|
||||||
Routes of administration |
Oral use
|
||||||
Dosage and administration details |
Disulfiram effervescent p.o. tablets 400mg daily, continuously. Disulfiram tablet must be dissolved in glass of water and mix immediately before use. It should be taken after evening meal, once daily, every day. No premedication or patient monitoring after administration of Disulfiram is required. Patients will take disulfiram after their evening meal. Treatment will take until progression or unacceptable toxicit or could be continued at the discretion of investigator in case that patient benefit from the treatment. In case of intolerance doses will be reduced for hematological and other toxicity. Dose adjustments are to be made according to the system showing the greatest degree of toxicity. In case of intolerance, lower dose up to 200 mg per day is allowed. Patients will avoid alcohol and other disulfiram-drug interactions will be considered.
|
||||||
|
|||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cisplatin + Disulfiram
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment. | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Overall study (overall period)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Cisplatin + Disulfiram
|
||
Reporting group description |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment. | ||
Subject analysis set title |
Overall study (overall period)
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Cisplatin will be administered intravenously 50mg/m2 day 1 and 2, every 3 weeks, Disulfiram 400mg daily p.o. continuously. Cycles will be repeated every 21 days until progression or unacceptable toxicity or up to 4 cycles of treatment. Treatment could be continued at the discretion of investigator in case that patient benefit from the treatment.
|
||
|
||||||||||
End point title |
Overall response rate | |||||||||
End point description |
Objective response rate is defined as sum of complete and partial responses.
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Objective response rate was calculated from the start of the treatment until progression or death.
|
|||||||||
|
||||||||||
| Notes [1] - None of patients achieved objective response to treatment so the study was terminated in first stage [2] - None of patients achieved objective response to treatment so the study was terminated in first stage |
||||||||||
Statistical analysis title |
Intention-to treat analysis | |||||||||
Comparison groups |
Cisplatin + Disulfiram v Overall study (overall period)
|
|||||||||
Number of subjects included in analysis |
24
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
other | |||||||||
P-value |
< 5 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
||||||||||
|
|||||||||||||
End point title |
Progression-free survival | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
The progression-free survival was calculated from the beginning of the treatment until progression or death from disease-specific cause on intention-to-treat basis.
|
||||||||||||
|
|||||||||||||
| Notes [3] - Median progression-free survival was 1.4 months, 95% CI (0.7 – 1.5 months) [4] - Median progression-free survival was 1.4 months, 95% CI (0.7 – 1.5 months) |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Overall survival | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Overall survival (OS) was be calculated from the beginning of the treatment until death from any cause on intention-to-treat basis.
|
||||||||||||
|
|||||||||||||
| Notes [5] - median overall survival was 2.9 months 95% CI (1.5 – 4.7 months) [6] - median overall survival was 2.9 months 95% CI (1.5 – 4.7 months) |
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events and serious adverse events were evaluated in all patients from the time of first administration of any study drug until 28 days after after disulfiram or cisplatin discotinuation, which one was later.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Adverse eventse were be monitored on an ongoing basis. Adverse events were categorized using the NCI Common Terminology Criteria for Adverse Events, Version 5.0.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
all subjects
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Adverse events and serious adverse events will be evaluated in all patients from the time of first administration of the Disulfiram with cisplatin until 28 days after after disulfiram or cisplatin discotinuation, which one was later.Adverse events will be monitored on an ongoing basis. Adverse events will be categorized using the NCI Common Terminology Criteria for Adverse Events, Version 5.0. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Apr 2019 |
Protocol ver.2.0 of 24 April 2019, summary of changes to Protocol ver.1.0 of 23 Jan 2019:
- section Contact addresses was amended
- section 1.4 /Pharmaceutical Data of Study Drugs was amended with Composition, storage and route of adminístraton for Disulfiram ad Cisplatin
- section 5.2 Concomitant medicaton was updated with Box 1: Other indications
- section 16. Administrative responsibiities was added
|
||
18 Oct 2019 |
Protocol ver.3.0 dated 18 Oct 2019, summary of changes to Protocol 2.0 dated 24 April 2019:
- Change of screening period from 21 to 28 days
- added chapter 8.0 Biological sampling
- Change of Monitor |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
