Everolimus for Patients With Relapsed/Refractory Germ Cell Cancer (RADIT)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Single Arm, Open-label Multicenter Phase II Trial of Everolimus in Patients With Relapsed/Refractory Germ Cell Cancer|
- Progression-free rate at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Percentage of patients that have not progressed after 12 weeks of treatment.
- Objective response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Safety profile [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2010|
|Study Completion Date:||March 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
|Experimental: Everolimus 10 mg daily||
Everolimus 10 mg orally per day.
Other Name: Afinitor
Patients with metastatic germ cell cancer and relapse after two or more courses of cisplatin-based chemotherapy or after high-dose chemotherapy have a poor prognosis and few treatment options. Everolimus is a derivative of rapamycin and acts as a signal transduction inhibitor. Its target is mTOR (mammalian target of rapamycin), a key protein kinase regulating cell growth, proliferation and survival. The mTOR pathway activity is modulated by the PI3K1AKT pathway and is known to be deregulated in numerous human cancers, including germ cell tumors. Everolimus is being investigated as an anticancer agent based on its potential to act:
- Directly on tumor cells by inhibiting tumor cell growth and proliferation
- Indirectly by inhibiting angiogenesis leading to reduced tumor vascularity
An open-label, single arm, non-randomized, single stage phase II study. Screening phase: Baseline evaluations will be performed within 2 weeks before the first dose of study drug. Treatment phase: All patients will receive everolimus until disease progression (by RECIST or tumor markers) or unacceptable toxicity or study discontinuation for other reasons. A treatment cycle consists of 3 weeks. Dose reductions and dose interruptions (for up to 2 weeks) are allowed for intolerable toxicity. Follow-up phase: All patients will be followed for survival.
Tumor Response and progression will be assessed using the RECIST criteria and assessments with tumor markers. Tumor measurements by a CT scan or MRI will be performed at screening within 2 weeks prior to the first dose of study drug. During the study period, the CT scan/MRI will be performed every 6 weeks (± one week), and at the time of discontinuation of study drug (within 2 weeks). The same type of scan (CT or MRI) used at screening must be used for all subsequent follow-up assessments. A partial or a complete response warrants a confirmation no sooner than 4 weeks and no later than 6 weeks after its observation.
Tumor markers (AFP, HCG) will be assessed every 3 weeks. A tumor marker reduction > 90% without an increase in tumor size is considered a partial response. A tumor marker increase > 25% without an increase in tumor size is considered progressive disease when confirmed 3 weeks after its observation.
The following retrospective pathological examinations of tumor samples will be performed in those patients that gave additional informed consent:
- immunohistochemistry for the mismatch repair genes hMLH1, hMSH2, hMSH6, and PMS2, and the cell signalling effectors pMAPK, pAKT, pS6K and PTEN.
- mutation analysis for PTEN, BRAF, p53, and examination of microsatellite instability This information will be correlated with treatment response (CR, PR, SO or PD) at week 12 in an exploratory analysis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01242631
|Vivantes Klinikum am Urban|
|Berlin, Germany, 10967|
|Essen, Germany, 45122|
|Hamburg, Germany, 20246|
|Hannover Medical School|
|Hannover, Germany, 30625|
|Universitatsklinikum Schieswig-Holstein - Campus Kiel|
|Kiel, Germany, 24105|
|Marburg, Germany, 35043|
|Klinikum Harlaching München|
|München, Germany, 81545|
|Universitatsklinikum der Eberhard-Karls-Universitat Tübingen|
|Tübingen, Germany, 72076|
|Principal Investigator:||Martin H Fenner, MD||Hannover Medical School|