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A Safety Study of LBH589 (Panobinostat) and RAD001 (Everolimus) to Stabilize Kidney Cancer

2014-08-27 03:17:06 | BioPortfolio

Summary

This study will see how these two commonly used treatments (Everolimus and Panobinostat) work together in treating kidney cancer. These two drugs have already progressed through the earliest types of research trials, such as a dose finding trial. We will combine these drugs at doses that were found to be safe when given alone, and will watch participants carefully to determine how well this drug combination is working to control your kidney cancer.

Description

The tyrosine kinase inhibitors sunitinib and sorafenib which target the VEGF pathway are now standard of care for renal cell carcinoma patients and are used as first-line agents.

mTOR inhibitors which have been shown to have direct antitumor effects against renal cell carcinoma cells and also decrease angiogenesis by downregulation of HIF-1ά are another promising class of agents in renal cell carcinoma. Recently, the mTOR inhibitor temsirolimus was approved as a first-line agent for metastatic renal cell carcinoma in patients with decreased performance status. An improvement in overall-survival was seen when compared to the interferon alpha treatment group.

We have recently shown in preclinical studies that HDAC inhibitors induce HIF-1ά inhibition by increased acetylation and polyubiquitination and subsequently increased degradation. Furthermore, in preclinical models we have demonstrated the in vivo and in vivo antiangiogenic activity for the single agent LBH589.

Based on these data, we hypothesized that the combination of a HDAC inhibitor and an mTOR inhibitor may have greater antiangiogenic and antitumor activity than single agents in a renal cell carcinoma model.

Taken together, these data suggests that the antiangiogenic activity of the HDAC inhibitor LBH589 and its direct antitumor effect may increase the therapeutic effect of RAD001, further delay disease progression and increase progression-free survival in patients with metastatic renal cell carcinoma (RCC). With this clinical trial, we will test for the efficacy of this particular combination as second line treatment in patients with metastatic renal cell carcinoma progressing after prior cytokine and /or tyrosine kinase inhibitor treatment.

This is a dose escalation study. The Phase II dose will be based upon Phase I findings. Patients will be allowed to remain on therapy provided that they are tolerating therapy and do not develop progressive disease.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Renal Cell Carcinoma

Intervention

LBH589 (Panobinostat) and RAD001 (Everolimus)

Location

Roswell Park Cancer Institute
Buffalo
New York
United States
14263

Status

Recruiting

Source

Roswell Park Cancer Institute

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:17:06-0400

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Panobinostat (LBH589) Plus Everolimus (RAD001) in Patients With Relapsed and Refractory Lymphoma

The goal of Phase 1 of this clinical research study is to learn the highest tolerable dose of the combination of LBH589 (panobinostat) and RAD001 (everolimus) that can be given to patients...

LBH589 Alone or in Combination With Erythropoietin Stimulating Agents (ESA) in Patients With Low or Int-1 Risk MDS

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The purpose of this study is evaluate the response, safety and tolerability in subjects receiving the investigational drugs (RAD001 and LBH589), when each investigational drug is given by ...

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Study of Panobinostat in Patients With Neuroendocrine Tumors

This summary will use Panobinostat (LBH589) in patients with neuroendocrine tumors to see how the patient's tumor responds to panobinostat. Additionally, this study will examine how long i...

PubMed Articles [19388 Associated PubMed Articles listed on BioPortfolio]

Attenuation of everolimus-induced cytotoxicity by a protective autophagic pathway involving ERK activation in renal cell carcinoma cells.

The mammalian target of rapamycin (mTOR) pathway is a critical target for cancer treatment and the mTOR inhibitor everolimus (RAD001) has been approved for treatment of renal cell carcinoma (RCC). How...

Safety and Efficacy of Cabozantinib in Metastatic Renal-Cell Carcinoma: Real-World Data From an Italian Managed Access Program.

The randomized phase 3 METEOR study confirmed a survival benefit of cabozantinib over everolimus in patients with metastatic renal-cell carcinoma (mRCC) with disease that progressed after treatment wi...

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment.

Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling.

Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chem...

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England.

The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular e...

Medical and Biotech [MESH] Definitions

A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.

An autosomal dominant disorder caused by mutations in a tumor suppressor gene. This syndrome is characterized by abnormal growth of small blood vessels leading to a host of neoplasms. They include HEMANGIOBLASTOMA in the RETINA; CEREBELLUM; and SPINAL CORD; PHEOCHROMOCYTOMA; pancreatic tumors; and renal cell carcinoma (see CARCINOMA, RENAL CELL). Common clinical signs include HYPERTENSION and neurological dysfunctions.

A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.

A rare tumor of the female genital tract, most often the ovary, formerly considered to be derived from mesonephric rests. Two varieties are recognized: (1) clear cell carcinoma, so called because of its histologic resemblance to renal cell carcinoma, and now considered to be of muellerian duct derivation and (2) an embryonal tumor (called also ENDODERMAL SINUS TUMOR and yolk sac tumor), occurring chiefly in children. The latter variety may also arise in the testis. (Dorland, 27th ed)

A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245)

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