E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
platina refractory testicular germ cell cancer |
platina refraktérny karcinom testikularnych germinativnych buniek |
|
E.1.1.1 | Medical condition in easily understood language |
testicular cancer |
nador semenikov |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061184 |
E.1.2 | Term | Germ cell cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | 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). |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate (ORR) by RECIST 1.1 (intent-to-treat population) |
|
E.5.1.1 | 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 |
|
E.5.2 | 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)
|
|
E.5.2.1 | 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
adverse events -until safety follow up
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
12 subjects will be enrolled in the first stage. If no responses are determined in the initial stage, the study will be concluded. If at least 1 patient achieved a partial or complete response, then the treatment will be considered worthy of further investigation and 8 more subjects will be accrued in the second stage for a total sample size of 20 subjects. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |