Study of Everolimus and Low-dose Cyclophosphamide in Patients With Metastatic Renal Cell Cancer

Summary

In the present phase 1-2 study the investigators aim to determine whether depletion of Tregs using metronomic cyclophosphamide can enhance the antitumor efficacy of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase 1 part of the study the investigators will determine the optimal CD4+CD25+ regulatory T cell-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with a fixed dose (10 mg daily) of everolimus. In the phase 2 part of the study the investigators will subsequently evaluate whether the number of patients who are cancer progression free at 4 months can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase 1 part) to everolimus. In addition to efficacy, the investigators will evaluate treatment toxicity to determine whether this combination strategy is feasible and safe.

Timeline

Start

2011-10

Primary completion

2017-01

Completion

2017-01

Publications

• Huijts CM, Werter IM, Lougheed SM, Goedegebuure RS, van Herpen CM, Hamberg P, Tascilar M, Haanen JB, Verheul HM, de Gruijl TD, van der Vliet HJ; Dutch WIN-O Consortium. Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother. 2019 Feb;68(2):319-329. doi: 10.1007/s00262-018-2248-3. Epub 2018 Nov 9.
• Huijts CM, Santegoets SJ, van den Eertwegh AJ, Pijpers LS, Haanen JB, de Gruijl TD, Verheul HM, van der Vliet HJ. Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer. BMC Cancer. 2011 Nov 30;11:505. doi: 10.1186/1471-2407-11-505.

Drugs

Indications