NCT01462214

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

Phase 1-2 Study of Everolimus and Low-dose Cyclophosphamide in Patients With Metastatic Renal Cell Cancer.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Hans J. van der Vliet, MD, PhD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a phase I/II, national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with fixed dose everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. Phase I part: Patients will be enrolled in cohorts of 5 per dose level. The first 5 patients enrolled will be assigned to dose level 0 in order to assess immune and angiogenic effects caused by everolimus monotherapy. The second 5 patients enrolled will be assigned to dose level 1. If there are ≤1 dose-limiting toxicities (DLTs) experienced by the first 5 patients in a cohort during the first 28 days after the first study treatment, further patients will be entered in the next dose level. Entry of patients into the expansion cohort will not occur until at least 28 days after the last patient in the escalation phase received his/her first study treatment. At the final dose level recommended for the phase II study a minimum of 10 patients will be treated. Phase II part: In the phase 2 part of the study up to 56 patients will be treated at the dose level that has been selected based on its capacity to most selectively deplete circulating Treg levels in the phase 1 part of the study. Based on data of patients with mRCC treated with everolimus monotherapy after previous treatment with sunitinib ± sorafenib, the investigators aim to increase the number of patients who are alive and cancer progression free at 4 months from 50% to 70% by adding metronomic cyclophosphamide. In addition, the investigators consider this increase meaningful as long as the combination treatment does not cause combination treatment related toxicity ≥ grade 3 in ≥ 30% of patients.

Conditions

• Metastatic Renal Cell Cancer

Interventions

Type	Name	Description
DRUG	Everolimus	Patients will be treated with low-dose oral cyclophosphamide (8 different dose levels and schedules) in combination with fixed dose (10 mg) everolimus in patients with mRCC.

Timeline

• Start date: 2011-10-01
• Primary completion: 2017-01-01
• Completion: 2017-01-01
• First posted: 2011-10-31
• Last updated: 2017-05-10

Locations

13 sites across 1 country: Netherlands