Everolimus in Refractory Testicular Germ Cell Cancer

Study Overview
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Brief Summary
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Everolimus in refractory testicular germ cell cancer. Everolimus 10 mg /day/ is administered to the patient until progression, unacceptable toxicity, complete response or inability of the subject to comply with study requirements. Feasibility of surgical resection will be assessed after every 2 cycles of the treatment in patients with partial response.

Detailed Description
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Treatment Schedule: Everolimus will be administered at a dose of 10mg/day orally once a day. One cycle of therapy consists of 28 days. Estimated duration of treatment: Until progression, unacceptable toxicity, complete response or inability of the subject to comply with study requirements. Feasibility of surgical resection will be assessed after every 2 cycles of the treatment in patients with partial response.

Official Title
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Phase II Study of Everolimus in Refractory Testicular Germ Cell Cancer.

Conditions
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Germ Cell Tumor

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Men aged 18 years or older ECOG performance status: 0-2, Histological confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer Refractory GCTs e.g. 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, Measurable disease radiological Adequate hematologic function defined by WBC > 4000/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 < 2,5 ULN and adequate renal function defined by serum creatinine ≤ 1.5 x ULN. At least 2 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, - Exclusion Criteria: Patients who do not fit inclusion criteria, Other prior malignancy except successfully treated non melanoma skin cancer Prior treatment with mTOR inhibitor No other concurrent approved or investigational anticancer treatment, including surgery, radiotherapy, chemotherapy, biologic-response modifiers, hormone therapy, or immunotherapy Female patients, Patients infected by the Human Immunodeficiency Virus (HIV), 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, Inability of oral intake, or drug absorption (e.g. malabsorption syndrome) Hypersensitivity to any compound of the drug, Sexually active men not using effective birth control if their partners are women of child-bearing potential. Patients with active CNS metastasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: everolimus 10 mg po daily<br>everolimus 10 mg po daily | Drug: Everolimus<br>* Tablets p.o. 10 mg daily until progression, unacceptable toxicity, complete response or inability of the subject to comply with study requirements.<br>* Other names: Afinitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | according RECIST criteria version 1.1 | 36 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Favorable response rate | complete response with chemotherapy and/or surgery, partial response marker negative. | 36 month | 
| Clinical benefit rate | (complete and partial response and stable disease > 6 months) | 36 month | 
| Progression-free survival | expressed as median and as 12-weeks post-treatment initiation continuous progression-free survival rate | 36 month | 
| Toxicity |  | 36 month | 
| Frequency of grade III and IV adverse events |  | 36 month | 
| Association between clinical outcome and biomarkers |  | 36 month | 
| Serum tumor markers response | >90% decline of AFP and/or HCG | 36 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory germ cell cancer, everolimus