Dornase Alfa and Cisplatin in Refractory Germ Cell Cancer.

NCT07121322 | Recruiting Phase 2

• 1 other identifier: GCT-SK-007
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Refractory Germ Cell Tumors; Dornase Alfa

Keywords

dornase alfa; refractory germ cell tumors

Outcome Measures

Primary Outcomes (1)

• 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)

  From enrollment to the end of treatment at 12 weeks

Secondary Outcomes (4)

• Overall response rate

  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.

• 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.

• Frequency of treatment related adverse events

  From baseline through study completion, an average of 1 year

Study Arms (1)

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

Drug: dornase alfa i.v. and cisplatin

Interventions

dornase alfa i.v. and cisplatin DRUG

Cisplatin 100mg/m2 day 1, every 3 weeks, Dornase alfa 125 microgram/kg day 1-5 i.v. push over 30 seconds±5 seconds

Dornase alfa and cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Cancer Institute, Slovakia: lead

Study Sites (1)

National Cancer Institute

Bratislava, 83101, Slovakia

RECRUITING

MeSH Terms

Conditions

Neoplasms, Germ Cell and Embryonal

Interventions

Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Michal Mego, prof.

  National Cancer Institute (NCI)

  STUDY CHAIR

Central Study Contacts

Michal Mego, Prof, MD, DSc

CONTACT

259378108; michal.mego@nou.sk

Daniela Svetlovska, PhD

CONTACT

259378592; daniela.svetlovska@nou.sk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Non-randomized, open-label, single center trial.

Study Record Dates

• First Submitted: July 22, 2025
• First Posted: August 13, 2025
• Study Start: July 30, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)