Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma
Summary
The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarcevaâ„¢) and sirolimus (Rapamuneâ„¢) in the treatment of patients with metastatic kidney cancer.
Description
Despite recent advances metastatic renal cell carcinoma remains an incurable condition. Currently available treatment with high-dose interleukin-2 can lead to complete responses in a small minority of selected patients but is markedly toxic and not broadly available. FDA-approved multikinase inhibitors (sorafenib and sunitinib malate) often cause partial and transient tumor regression. There is no standard treatment metastatic renal cell carcinoma for patients whose disease progressed on multikinase inhibitors. The kinase mammalian target of rapamycin (mTOR) is overstimulated in a subset of renal cell carcinomas and other malignancies and can be blocked by sirolimus leading to growth arrest. Erlotinib hydrochloride is a drug that blocks the function of the epidermal growth factor receptor (EGFR), often over expressed in kidney cancer. Sirolimus and EGFR inhibitors and been safely used in combination. In vitro experiments show that erlotinib enhances the sirolimus induced growth impairment in a panel of renal cell carcinoma cells. In the present study patients with metastatic renal cell carcinoma whose disease progressed on multikinase inhibitors will be treated with the combination of erlotinib hydrochloride (Tarcevaâ„¢) and sirolimus (Rapamuneâ„¢). This is a single arm trial with no placebo or drug-based control arm
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Renal Cell Carcinoma
Intervention
Erlotinib hydrochloride, Sirolimus
Location
University of Colorado Hospital
Aurora
Colorado
United States
80010
Status
Completed
Source
University of Colorado, Denver
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00353301
- Information obtained from ClinicalTrials.gov on May 19, 2013
Medical and Biotech [MESH] Definitions
Carcinoma, Renal Cell
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.
Von Hippel-lindau Disease
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.
Carcinoma, Non-small-cell Lung
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.
Mesonephroma
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)
Carcinoma, Merkel Cell
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)
Clinical Trials
Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma
RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects a...
The primary purpose of the study is to assess the potential benefit of combining two targeted therapies (an anti-EGF inhibitor along with an anti-VEGF inhibitor). The goal will be to dete...
Ph II Erlotinib + Sirolimus for Pts w Recurrent Malignant Glioma Multiforme
Primary objective: To determine the 6-month progression free survival of patients with recurrent GBM treated with Erlotinib plus Sirolimus. Secondary objectives: To further...
Erlotinib in Treating Patients With Locally Advanced or Metastatic Papillary Renal Cell Cancer
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treat...
Evaluation of Bay 59-8862 in Patients With Advanced Renal Cell Carcinoma
In patients with renal cell cancer, most frequent methods of treatment include surgery, chemotherapy, hormonal therapy, and immunotherapy. Renal cell carcinoma is usually considered to be...
PubMed Articles
Background:The mammalian target of rapamycin (mTOR) is an important therapeutic target in the treatment of renal cell carcinoma (RCC). Pre-clinical data indicate that the combined inhibition of both t...
In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus fo...
The incidence of native kidneyrenal cell carcinoma (RCC) in renal transplantrecipients is 15 times higher than thegeneral population. These tumors are oftenfound incidentally when imaging is performed...
Sirolimus therapy may cause cardiac tamponade.
The side-effects associated with the immunosuppressive drug sirolimus are numerous and constitute a major limitation for its use in renal transplantation. In this study, we describe two cases of renal...
