NCT07121322 Dornase Alfa and Cisplatin in Refractory Germ Cell Cancer.

Eligibility & Interventions

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What to Expect as a Participant

You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.

In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.

This trial targets 33 participants in total. It began in 2025-07-30 with a primary completion date of 2027-07-30.

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.

Eligibility Criteria

Inclusion Criteria: 1. Signed written informed consent. 2. Adult men aged 18 years or older. 3. ECOG (Eastern Cooperative Oncology Group) performance status: 0-1. 4. Histologically confirmed extracranial primary germ cell cancer, seminoma, or non-seminoma. 5. Rising serum markers (i.e., alfa-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. RECIST 1.1 measurable disease. 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. 17. 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. Exclusion Criteria: 1. Patients who do not fit inclusion criteria. 2. Other prior malignancy except successfully treated nonmelanoma skin cancer . 3. Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy. 4. Female patients. 5. 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. 6. 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. 7. 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).

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