Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
Primary Purpose
Metastatic Renal Cell Carcinoma
Status
Completed
Phase
Phase 4
Locations
Russian Federation
Study Type
Interventional
Intervention
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring renal cell carcinoma, kidney cancer, bevacizumab failure, everolimus
Eligibility Criteria
Inclusion Criteria:
- Histologically proven renal cell carcinoma
- CT-confirmed measurable disease
- Disease progression after bevacizumab +/- IFN
- Favorable/intermediate prognosis according to MSKCC
- Nephrectomy
- No contradictions to everolimus
- Age 18 or older
- Written informed consent
Exclusion criteria
- prior TKI's or mTOR inhibitor
- pregnant or nursing
- history of serious cardiac arrhythmia, congestive heart failure, angina pectoris, or other severe cardiovascular disease (i.e., New York Heart Association class III or IV)
- CNS metastases by neurologic exam and/or MRI
- local and/or systemic infections requiring antibiotics within 28 days prior to study entry
- other malignancy
Sites / Locations
- Tatarstan Regional Cancer Center
- Altai Regional Cancer Center
- N.N. Blokhin Russian Cancer Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Everolimus
Arm Description
All patients with metastatic renal cell carcinoma progressing on prior treatment with bevacizumab ± interferon enrolled into this study will receive everolimus in the dose of 10 mg daily until the disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study)
Secondary Outcome Measures
Median progression-free survival
Median overall survival
Response rate according to RECIST 1.1
Treatment safety and tolerability according to NCI-CTCAE v.4.0
Full Information
NCT ID
NCT02056587
First Posted
February 4, 2014
Last Updated
February 5, 2014
Sponsor
Kidney Cancer Research Bureau
1. Study Identification
Unique Protocol Identification Number
NCT02056587
Brief Title
Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
Official Title
Everolimus (Afinitor) in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kidney Cancer Research Bureau
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An estimated 10,000 metastatic renal cell carcinoma (RCC) patients receive first-line therapy in the Russian Federation. Bevacizumab (Avastin) in combination with interferon-alpha (IFN) is a recommended first-line treatment for metastatic RCC according to clinical recommendations of Russian Ministry of Health from 15.07.2010. Two randomized phase III trials (AVOREN, CALGB) showed that 50% of patients will progress on bevacizumab plus IFN within 8.5 - 10.2 months and will need sequential therapy.
Everolimus (Afinitor) is a single agent which was evaluated and demonstrated efficacy in randomized phase III study (RECORD-1) in metastatic RCC patients after failure of targeted therapy. However, in this trial everolimus was compared with placebo for the treatment of patients whose disease had progressed on treatment with sunitinib or sorafenib (n=227). Only 9% (n=24) of patients received bevacizumab. Thus, efficacy data of everolimus in patients with disease progression on first-line bevacizumab is limited.
Evaluating the effectiveness of everolimus in metastatic RCC patients with failure on bevacizumab with/without interferon alpha has a scientific and practical sense, and it is important for Russian Federation.
Detailed Description
17563 new cases of renal cancer and 83790 associated deaths have recorded in the Russian Federation in 2008. Renal cell carcinoma (RCC) is responsible for 4,3% of all malignancies, with increased risk of disease after the age of 60 years. Renal cell carcinoma accounts for 90% renal neoplasms, and in 85% of renal cell carcinoma cases light-cell morphology is diagnosed. Papillary, chromophobic cancer and cancer of the kidney collecting tubules.
30% patients with localized renal cell carcinoma are found to progress after surgical treatment. In the other 30% renal cell carcinoma is established at the dissemination stage. Therefore approximately 60% of renal cell carcinoma patients are estimated to have metastases.
According to estimations by Kidney Cancer Research Bureau, currently first line treatment is indicated to approximately 10,000 patients with metastatic renal cell carcinoma in Russia annually.
Until recently opportunities for systemic treatment in metastatic renal cell carcinoma were limited to administration of cytokines and clinical research investigating novel medications. Various combinations and doses of interleukin-2 (IL-2) and interferon-alpha (IFN) have been investigated in randomized studies in metastatic renal cell carcinoma. Immunotherapy was found to have only limited efficacy (overall response rate 15-16%, survival of 12 months). Therefore target medicines, specifically - tyrosine kinase inhibitors and mTOR inhibitors, are under development as first and subsequent lines of treatment.
According to standards of medical care established by the Ministry of Health and Social Development of the Russian Federation as of July 15, 2010, combination of bevacizumab (Avastin™) and interferon is recommended as first line treatment. According to two randomized phase III trials (AVOREN, CALGB) more than half of patients are expected to require further treatment for disease progression in 8,5-10,2 months. Everolimus (Afinitor) is the only medicine that has been investigated in a phase III multicenter study (RECORD-1) as second and subsequent lines of treatment for metastatic renal cell carcinoma resistant to targeted agents. However, most patients (n=277) had received sunitinib or sorafenib prior to enrolment; only some of them (24 patients (9%) had received bevacizumab. Therefore currently convincing evidence of everolimus efficacy after progression on prior treatment with bevacizumab or bevacizumab + IFN is lacking.
Hence it is deemed reasonable and practically relevant to investigate everolimus efficacy in patients with metastatic renal cell carcinoma previously treated on bevacizumab-containing regimens, in the Russian Federation.
Efficacy endpoints
Primary:
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study)
Secondary:
Median progression-free survival and overall survival from the time of enrolment Response rate, according to RECIST 1.1 Treatment safety and tolerability according to NCI-CTCAE v.4.0 Patients quality of life, according to EORTC QLQ-C30 questionnaire
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Renal Cell Carcinoma
Keywords
renal cell carcinoma, kidney cancer, bevacizumab failure, everolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
All patients with metastatic renal cell carcinoma progressing on prior treatment with bevacizumab ± interferon enrolled into this study will receive everolimus in the dose of 10 mg daily until the disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
All patients with metastatic renal cell carcinoma progressing on prior treatment with bevacizumab ± interferon enrolled into this study will receive everolimus in the dose of 10 mg daily until the disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study)
Time Frame
2 months
Secondary Outcome Measure Information:
Title
Median progression-free survival
Time Frame
12 months
Title
Median overall survival
Time Frame
24 months
Title
Response rate according to RECIST 1.1
Time Frame
24 months
Title
Treatment safety and tolerability according to NCI-CTCAE v.4.0
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven renal cell carcinoma
CT-confirmed measurable disease
Disease progression after bevacizumab +/- IFN
Favorable/intermediate prognosis according to MSKCC
Nephrectomy
No contradictions to everolimus
Age 18 or older
Written informed consent
Exclusion criteria
prior TKI's or mTOR inhibitor
pregnant or nursing
history of serious cardiac arrhythmia, congestive heart failure, angina pectoris, or other severe cardiovascular disease (i.e., New York Heart Association class III or IV)
CNS metastases by neurologic exam and/or MRI
local and/or systemic infections requiring antibiotics within 28 days prior to study entry
other malignancy
Facility Information:
Facility Name
Tatarstan Regional Cancer Center
City
Kazan
State/Province
Tatarstan
ZIP/Postal Code
420029
Country
Russian Federation
Facility Name
Altai Regional Cancer Center
City
Barnaul
Country
Russian Federation
Facility Name
N.N. Blokhin Russian Cancer Research Center
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
12. IPD Sharing Statement
Citations:
PubMed Identifier
25466382
Citation
Tsimafeyeu I, Snegovoy A, Varlamov S, Safina S, Varlamov I, Gurina L, Manzuk L. Everolimus in patients with metastatic renal cell carcinoma previously treated with bevacizumab: a prospective multicenter study CRAD001LRU02T. Target Oncol. 2015 Sep;10(3):423-7. doi: 10.1007/s11523-014-0347-4. Epub 2014 Dec 4.
Results Reference
derived
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Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
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