Trial reportBMC cancer2011
Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer.
Trial report in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01462214 (Phase 1-2 Study of Everolimus and Low-dose Cyclophosphamide in Patients With Metastatic Renal Cell Cancer.), which is not on this map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1-2 Study of Everolimus and Low-dose Cyclophosphamide in Patients With Metastatic Renal Cell Cancer.
Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus.Cancer immunology, immunotherapy : CII · 2019Trial
- Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.Pharmaceutics · 2025Review
- Remodeling the tumor microenvironment: regulatory effects of β-sitosterol and luteolin on the immunosuppressive milieu in endometrial carcinoma and implications for combinatorial immunotherapy.Frontiers in immunology · 2025Review
- Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?International journal of molecular sciences · 2021Review
- The effect of everolimus and low-dose cyclophosphamide on immune cell subsets in patients with metastatic renal cell carcinoma: results from a phase I clinical trial.Cancer immunology, immunotherapy : CII · 2019Article
- Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma.Cancer immunology, immunotherapy : CII · 2019Article
- The role of regulatory T cells in cancer immunology.ImmunoTargets and therapy · 2015Review
- Brain Tumor Immunotherapy: What have We Learned so Far?Frontiers in oncology · 2015Review
- Induction of apoptosis by luteolin involving akt inactivation in human 786-o renal cell carcinoma cells.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.Frontiers in immunology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFor patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide. METHODS/
designThis phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels. DISCUSSION: This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus.
trial registrationClinicalTrials.gov Identifier NCT01462214, EudraCT number 2010-024515-13, Netherlands Trial Register number NTR3085.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.