Study to evaluate effectiveness of disulfiram and cisplatin in patients with refractory testicular cancer.

Phase 1

• Conditions: platina refractory testicular germ cell cancer; MedDRA version: 20.0 Level: PT Classification code 10061184 Term: Germ cell cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000558-68-SK
• Lead Sponsor: árodný onkologický ústav

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-03-20
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 20

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)Measurable disease radiologically.
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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1)Patients who do not fit inclusion criteria.
2)Other prior malignancy except successfully treated nonmelanoma skin cancer.
3)Addiction to alcohol or drugs.
4)Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy.
5)Need for metronidazole, warfarin and/or theophylline medication, the metabolism of which is likely influenced by disulfiram (see Box 1).
6)Patients who are taking medications metabolized by cytochrome P450 2E1, including chlorzoxazone or halothane and its derivatives (see Box 1).
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

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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).;Secondary Objective: To describe the favorable response rate, progression-free survival rate, time to progression and toxic effects of disulfiram with cisplatin in patients with multiple relapsed/refractory metastatic germ cell cancer. ;Primary end point(s): Overall response rate (ORR) by RECIST 1.1 (intent-to-treat population);Timepoint(s) of evaluation of this end point: every 6 weeks, if patient is discontinued for unacceptable toxicity than every 8 weeks until disease progression or start of new anticancer treatment whatever comes first

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): Progression-free survival, Overall survival, Toxicity, Frequency of grade III and IV adverse events, Association between clinical outcome and biomarkers (exploratory analysis)<br> ;<br> Timepoint(s) of evaluation of this end point: efficacy -every 6 weeks, if patient is discontinued for unacceptable toxicity than every 8 weeks until disease progression or start of new anticancer treatment whatever comes first<br> <br> adverse events -until safety follow up<br>