Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer

• Status: Completed
• Trial end date: 2021-02-15
• Target enrollment: 0
• Participant gender: Male

Summary

This is a proof-of-concept study to define efficacy of gemcitabine, carboplatin and VELIPARIB (ABT-888) in patients with refractory germ cell tumors (GCTs). PARP proteins are involved in base excision repair (BER), one of the major DNA repair system in cells and PARP is overexpressed in testicular GCTs (TGCTs) compared to normal testis and data suggest that PARP overexpression is early event in TGCTs development. Patients with low PARP expression in primary tumour had non-significantly better OS compared to patients with high PARP expression (5-year OS 89.2% vs 78.7%; HR=0.50, 95% CI 0.21 to 1.17, p=0.12). The aim of this study is to evaluate PARP inhibitor VELIPARIB in combination with gemcitabine, carboplatin in patients with refractory germ cell tumors (GCTs).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute, Slovakia
• Treatments: Carboplatin; Gemcitabine; Veliparib

Criteria

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. Refractory GCTs e.g. 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 creatinine (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

Exclusion Criteria:

1. Patients who do not fit inclusion criteria

2. Other prior malignancy except successfully treated nonmelanoma skin cancer

3. Prior PARP1 inhibitor

4. Other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy

5. Female patients

6. Patients infected by the Human Immunodeficiency Virus (HIV)

7. 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

8. Inability of oral intake, or drug absorption (e.g. malabsorption syndrome)

9. Hypersensitivity to any compound of the drug

10. Sexually active men not using highly effective birth control if their partners are women of child-bearing potential

11. Patients with history of or current CNS metastasis

12. Patients with history of seizures