Refractory Germ Cell TumorsPhase 2DACT-GCTNCT07121322
Dornase Alfa and Cisplatin in Refractory Germ Cell Cancer.
A Phase 2 study testing dornase alfa i.v. and cisplatin in people with Refractory Germ Cell Tumors and Dornase Alfa, run by National Cancer Institute, Slovakia at 1 site in Slovakia.
Trial summary
Germ cell tumors (GCTs) are highly curable malignancies; however, a subset of patients with relapsed or refractory disease after first- and second-line chemotherapy have a very poor prognosis, with long-term survival rates below 5%. New therapeutic strategies are needed in this setting. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Refractory Germ Cell Tumors, Dornase Alfa
- What is being tested?
- dornase alfa i.v. and cisplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteSlovakia
- Study dates
- 30 Jul 2025to 30 Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent.
- Adult men aged 18 years or older.
- ECOG (Eastern Cooperative Oncology Group) performance status: 0-1.
- Histologically confirmed extracranial primary germ cell cancer, seminoma, or non-seminoma.
- Rising serum markers (i.e., alfa-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer.
- 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.
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- Primary mediastinal GCTs in first relapse.
- Patient's disease must not be amenable to cure with either surgery or chemotherapy in the opinion of investigator.
- RECIST 1.1 measurable disease.
- Adequate hematologic function defined by ANC > 1500/mm3, platelet count > 100 000/mm3 and hemoglobin level > 9g/dl.
- 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.
- 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)].
- At least 4 weeks must have elapsed since the last radiotherapy and/or chemotherapy before study entry.
- At least 4 weeks must have elapsed since the last major surgery.
- Complete recovery from prior surgery, and/or reduction of all adverse events from previous systemic therapy or radiotherapy to grade 1.
- Absence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- Male patients with a female partner of childbearing potential who agree to use an effective method of contraception (condom) and a highly effective method of contraception by their female partner during the study and 6 months after the last study treatment intake.
Who cannot join
- Patients who do not fit inclusion criteria.
- Other prior malignancy except successfully treated nonmelanoma skin cancer .
- Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy.
- Female patients.
- 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.
- Hypersensitivity to any compound of the drugs, severe known allergies or intolerance to other recombinant protein products obtained from Chinese hamster ovary cells according to Investigatorś decision.
- Known participation in another clinical trial investigating a drug and/or medical product in the last 30 days or 5 half-lives of the investigational drug and/or medicinal product (whichever is longer).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Slovakia1 site, 1 recruiting
- Recruiting
National Cancer Institute
Bratislava, 83101
Timea Farkasova, Ing, 259378592 ext. +421, timea.farkasova@nou.sk
Nora Palenikova, Ing, 259378592 ext. +421, nora.palenikova@nou.sk
About this study
Official title: Phase II Study of Dornase Alfa and Cisplatin in Refractory Germ Cell Cancer.
Germ cell tumors (GCTs) are highly curable malignancies; however, a subset of patients with relapsed or refractory disease after first- and second-line chemotherapy have a very poor prognosis, with long-term survival rates below 5%. New therapeutic strategies are needed in this setting. Emerging evidence indicates that extracellular DNA and markers of NETosis are associated with poor prognosis in GCTs, while DNase activity decreases with disease progression. Dornase alfa, a recombinant human DNase I approved for cystic fibrosis, may restore DNA homeostasis by degrading extracellular DNA. Preclinical studies demonstrated that dornase alfa, when combined with cisplatin, inhibited tumor growth in cisplatin-resistant GCT xenograft models. This proof-of-concept phase II study aims to evaluate the safety and efficacy of dornase alfa in combination with cisplatin in patients with relapsed or refractory GCTs, hypothesizing that extracellular DNA degradation by dornase alfa may enhance tumor control and restore cisplatin sensitivity.
Read the detailed description
Germ cell tumors (GCTs) represent a unique solid tumor entity with high curability even in metastatic disease, primarily due to their marked chemosensitivity. Despite this, a subset of patients with multiple relapsed or refractory GCTs fail to achieve long-term remission with currently available standard- or high-dose salvage regimens. Long-term survival after failure of second-line chemotherapy is below 5%, underscoring the urgent need for new therapeutic strategies.
Recent translational research has highlighted a potential role of extracellular DNA and NETosis (neutrophil extracellular trap formation) in the pathogenesis and progression of refractory GCTs. Plasma analyses in GCT patients revealed elevated levels of cell-free DNA and NETosis markers in association with poor prognosis and disease burden. Moreover, reduced DNase activity during disease progression suggests impaired clearance of extracellular DNA, which may contribute to resistance to cytotoxic therapy.
Dornase alfa is a recombinant human deoxyribonuclease I (DNase I) approved for use in cystic fibrosis, where it enzymatically degrades extracellular DNA and reduces mucus viscosity. Preclinical in vitro experiments in TGCT cell lines, including cisplatin-resistant models, confirmed that dornase alfa is non-toxic at clinically relevant concentrations and does not negatively affect proliferation or migration. Notably, in vivo data from cisplatin-resistant xenograft models demonstrated that the combination of dornase alfa and cisplatin led to significant tumor growth inhibition, suggesting a potential synergistic effect mediated via degradation of extracellular DNA.
This is a non-randomized, open-label, single-center phase II study evaluating the efficacy and safety of dornase alfa in combination with cisplatin in adult male patients with histologically confirmed extracranial, metastatic, and multiply relapsed or refractory GCTs. The trial employs a Simon's optimal two-stage design.
The primary objective is to determine the 12-week progression-free survival (PFS) in the intent-to-treat population. Secondary objectives include overall response rate (ORR), PFS, overall survival (OS), safety, and the frequency of grade III/IV adverse events. An exploratory objective is to evaluate the association between clinical outcomes and circulating biomarkers (serum/plasma levels of DNase, cell-free DNA, and NETs).
Patients will receive intravenous cisplatin 100 mg/m² on day 1 of each 21-day cycle. Dornase alfa will be administered intravenously at a dose of 125 µg/kg daily on days 1-5. On day 1, dornase alfa will be given 2-3 hours after completion of cisplatin infusion; on subsequent days (2-5), it will be administered at the same time of day (±2 hours). Treatment will continue until disease progression or unacceptable toxicity.
Pharmacokinetic and biomarker studies will be conducted in each treatment cycle, with serum and plasma samples collected on day 1 and day 5 before administration of dornase alfa, and 4 and 24 hours post-administration. These will be used to monitor DNase activity, levels of cell-free DNA, and NETosis-related markers.
This study aims to provide proof-of-concept clinical evidence that targeting extracellular DNA with dornase alfa may enhance the anti-tumor efficacy of cisplatin in patients with heavily pretreated GCTs.
- Conditions
- Refractory Germ Cell Tumors, Dornase Alfa
- Being tested
- dornase alfa i.v. and cisplatin
- Keywords
- dornase alfa, refractory germ cell tumors
- Medical subject headings
- Neoplasms, Germ Cell and Embryonal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dornase alfa i.v. and cisplatinDrug
Cisplatin 100mg/m2 day 1, every 3 weeks, Dornase alfa 125 microgram/kg day 1-5 i.v. push over 30 seconds±5 seconds
| Study group | Role | What they receive |
|---|---|---|
| Dornase alfa and cisplatin | Experimental | Cisplatin 100mg/m2 day 1, every 3 weeks, Dornase alfa 125 microgram/kg day 1-5 i.v. push over 30 seconds±5 seconds Receives: Drug: dornase alfa i.v. and cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-week progresion-free survival
12-week post-treatment initiation continuous progression-free survival rate will be summarized as counts and proportions with exact binomial 90% confidence interval (ITT population)
Measured: From enrollment to the end of treatment at 12 weeks
Secondary outcomes (4)
Overall response rate
Overall response rate (ORR) by RECIST 1.1 and tumor markers (AFP, HCG, LDH)
Measured: From the treatment initiation till the first response assessment at week 6
Progression-free survival
From the start of treatment (day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Measured: From the start of treatment (day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
Overall survival
Overall survival (OS) will be calculated from the start of treatment (day 1) until death from any cause assessed up to 100 months
Measured: Overall survival (OS) will be calculated from the start of treatment (day 1) until death from any cause assessed up to 100 months.
Frequency of treatment related adverse events
Treatment related adverse reaction according to common toxicity criteria
Measured: From baseline through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2025
- Study start30 Jul 2025
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Germ Cell TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Non-randomized, open-label, single center trial.
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Slovakia
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Michal Mego, prof., Study chair, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07121322
- Sponsor's protocol ID
- GCT-SK-007
- Acronym
- DACT-GCT
- Status last verified
- Sep 2026
- First submitted
- 22 Jul 2025
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: These data are confidential
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Dornase Alfa and Cisplatin in Refractory Germ Cell Cancer.
- ClinicalTrials.gov ID
- NCT07121322
- Acronym / sponsor ID
- DACT-GCT / GCT-SK-007
- Conditions
- Refractory Germ Cell Tumors, Dornase Alfa
- Keywords
- dornase alfa, refractory germ cell tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- National Cancer Institute, SlovakiaOther government
- Study start
- 30 Jul 2025 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Jul 2028 (estimated)
- First posted
- 13 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Germ cell tumors (GCTs) are highly curable malignancies; however, a subset of patients with relapsed or refractory disease after first- and second-line chemotherapy have a very poor prognosis, with long-term survival rates below 5%. New therapeutic strategies are needed in this setting. Emerging evidence indicates that extracellular DNA and markers of NETosis are associated with poor prognosis in GCTs, while DNase activity decreases with disease progression. Dornase alfa, a recombinant human DNase I approved for cystic fibrosis, may restore DNA homeostasis by degrading extracellular DNA. Preclinical studies demonstrated that dornase alfa, when combined with cisplatin, inhibited tumor growth in cisplatin-resistant GCT xenograft models. This proof-of-concept phase II study aims to evaluate the safety and efficacy of dornase alfa in combination with cisplatin in patients with relapsed or refractory GCTs, hypothesizing that extracellular DNA degradation by dornase alfa may enhance tumor control and restore cisplatin sensitivity.
Detailed description
Germ cell tumors (GCTs) represent a unique solid tumor entity with high curability even in metastatic disease, primarily due to their marked chemosensitivity. Despite this, a subset of patients with multiple relapsed or refractory GCTs fail to achieve long-term remission with currently available standard- or high-dose salvage regimens. Long-term survival after failure of second-line chemotherapy is below 5%, underscoring the urgent need for new therapeutic strategies.
Recent translational research has highlighted a potential role of extracellular DNA and NETosis (neutrophil extracellular trap formation) in the pathogenesis and progression of refractory GCTs. Plasma analyses in GCT patients revealed elevated levels of cell-free DNA and NETosis markers in association with poor prognosis and disease burden. Moreover, reduced DNase activity during disease progression suggests impaired clearance of extracellular DNA, which may contribute to resistance to cytotoxic therapy.
Dornase alfa is a recombinant human deoxyribonuclease I (DNase I) approved for use in cystic fibrosis, where it enzymatically degrades extracellular DNA and reduces mucus viscosity. Preclinical in vitro experiments in TGCT cell lines, including cisplatin-resistant models, confirmed that dornase alfa is non-toxic at clinically relevant concentrations and does not negatively affect proliferation or migration. Notably, in vivo data from cisplatin-resistant xenograft models demonstrated that the combination of dornase alfa and cisplatin led to significant tumor growth inhibition, suggesting a potential synergistic effect mediated via degradation of extracellular DNA.
This is a non-randomized, open-label, single-center phase II study evaluating the efficacy and safety of dornase alfa in combination with cisplatin in adult male patients with histologically confirmed extracranial, metastatic, and multiply relapsed or refractory GCTs. The trial employs a Simon's optimal two-stage design.
The primary objective is to determine the 12-week progression-free survival (PFS) in the intent-to-treat population. Secondary objectives include overall response rate (ORR), PFS, overall survival (OS), safety, and the frequency of grade III/IV adverse events. An exploratory objective is to evaluate the association between clinical outcomes and circulating biomarkers (serum/plasma levels of DNase, cell-free DNA, and NETs).
Patients will receive intravenous cisplatin 100 mg/m² on day 1 of each 21-day cycle. Dornase alfa will be administered intravenously at a dose of 125 µg/kg daily on days 1-5. On day 1, dornase alfa will be given 2-3 hours after completion of cisplatin infusion; on subsequent days (2-5), it will be administered at the same time of day (±2 hours). Treatment will continue until disease progression or unacceptable toxicity.
Pharmacokinetic and biomarker studies will be conducted in each treatment cycle, with serum and plasma samples collected on day 1 and day 5 before administration of dornase alfa, and 4 and 24 hours post-administration. These will be used to monitor DNase activity, levels of cell-free DNA, and NETosis-related markers.
This study aims to provide proof-of-concept clinical evidence that targeting extracellular DNA with dornase alfa may enhance the anti-tumor efficacy of cisplatin in patients with heavily pretreated GCTs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Non-randomized, open-label, single center trial.
| Arm | Type | Receives |
|---|---|---|
| Dornase alfa and cisplatin | Experimental | Drug: dornase alfa i.v. and cisplatinCisplatin 100mg/m2 day 1, every 3 weeks, Dornase alfa 125 microgram/kg day 1-5 i.v. push over 30 seconds±5 seconds |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed written informed consent.
- Adult men aged 18 years or older.
- ECOG (Eastern Cooperative Oncology Group) performance status: 0-1.
- Histologically confirmed extracranial primary germ cell cancer, seminoma, or non-seminoma.
- Rising serum markers (i.e., alfa-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer.
Key exclusion criteria (7 listed)
- Patients who do not fit inclusion criteria.
- Other prior malignancy except successfully treated nonmelanoma skin cancer .
- Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy.
- Female patients.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dornase alfa i.v. and cisplatinCisplatin 100mg/m2 day 1, every 3 weeks, Dornase alfa 125 microgram/kg day 1-5 i.v. push over 30 seconds±5 seconds | Drug | Dornase alfa and cisplatin |
Primary outcome
12-week progresion-free survival
Time frame: From enrollment to the end of treatment at 12 weeks
12-week post-treatment initiation continuous progression-free survival rate will be summarized as counts and proportions with exact binomial 90% confidence interval (ITT population)
4 secondary outcomes
Overall response rate
Time frame: From the treatment initiation till the first response assessment at week 6
Progression-free survival
Time frame: From the start of treatment (day 1) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.
Overall survival
Time frame: Overall survival (OS) will be calculated from the start of treatment (day 1) until death from any cause assessed up to 100 months.
Frequency of treatment related adverse events
Time frame: From baseline through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Individual participant dataSharing planned: No. These data are confidential
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michal Mego, prof. study chair
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dornase alfa i.v. and cisplatin in people with Refractory Germ Cell Tumors and Dornase Alfa, run by National Cancer Institute, Slovakia at 1 site in Slovakia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Slovakia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michal Mego, Prof, MD, DSc (259378108 ext. +421, michal.mego@nou.sk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
12-week progresion-free survival (time frame: From enrollment to the end of treatment at 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.