Een fase 1-2 studie van everolimus en lage dosis orale cyclofosfamide bij patiënten met uitgezaaide niercelkanker.
Recruiting
- Conditions
- Metastatic renal cell cancer.
- Registration Number
- NL-OMON21801
- Lead Sponsor
- VU University Medical Center
- Brief Summary
/A
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 96
Inclusion Criteria
1. Patients with histologically or cytologically confirmed clear-cell mRCC with progressive disease and not amenable to or progressive on or within 6 months of stopping treatment with a VEGF receptor tyrosine kinase inhibitor (sunitinib (or pazopanib) ¡À sorafenib);
2. Prior therapy with cytokines (i.e. IL-2, interferon) and/or VEGF-ligand inhibitors (i.e. bevacizumab) is permitted;
Exclusion Criteria
1. Patients currently receiving chemotherapy, immunotherapy, or radiotherapy or who have received these <= 4 weeks prior to visit 1. The wash-out period for sunitinib or sorafenib is at least 2 weeks from the first dose of the study medication;
2. Known human immunodeficiency virus (HIV) or other major immunodeficiency;
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase I:<br /><br>1. Assessment of the recommended dosing and schedule for metronomic cyclophosphamide when administered in combination with fixed dose (10 mg) oral everolimus in patients with mRCC with respect to the selective induction of CD4+CD25+ regulatory T cell depletion;<br /><br>2. Assessment of safety and tolerability for the combination of metronomic cyclophosphamide and fixed dose oral everolimus in patients with mRCC. <br><br /><br /><br>Phase II: <br /><br>1. To investigate the proportion of patients with mRCC receiving everolimus and metronomic cyclophosphamide that is alive and progression-free at 4 months;<br /><br>2. Assessment of safety and tolerability for the combination of metronomic cyclophosphamide and fixed dose oral everolimus in patients with mRCC.
- Secondary Outcome Measures
Name Time Method Phase I and II study:<br /><br>1. To assess the response rate, time to progression, and overall survival of the combination of metronomic cyclophosphamide and fixed dose oral everolimus in patients with mRCC;<br /><br>2. Assessment of the immunological effects of combining metronomic cyclophosphamide with everolimus;<br /><br>3. Assessment of the effect of the combination of metronomic cyclophosphamide and everolimus on selected angiogenesis parameters;<br /><br>4. To assess whether intrapatient changes in thrombocyte numbers correlate with response rate and/or time to progression in patients using the combination of metronomic cyclophosphamide and fixed dose oral everolimus;<br /><br>5. To asess the effects of the combination of metronomic cyclophosphamide and everolimus on tumor-infiltrating leukocytes, including CD4+CD25+FOXP3+ regulatory T cells;<br /><br>6. To assess the effects of cyclophosphamide administration on the pharmacokinetics of everolimus.