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Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment

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ClinicalTrials.gov Identifier: NCT02056587
Recruitment Status : Completed
First Posted : February 6, 2014
Last Update Posted : February 6, 2014
Sponsor:
Information provided by (Responsible Party):
Kidney Cancer Research Bureau

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.


Condition or disease Intervention/treatment Phase
Metastatic Renal Cell Carcinoma Drug: Everolimus Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Everolimus (Afinitor) in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
Study Start Date : November 2011
Actual Primary Completion Date : April 2013
Actual Study Completion Date : October 2013


Arm Intervention/treatment
Experimental: Everolimus
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.
Drug: Everolimus
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 Measures :
  1. 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 Measures :
  1. Median progression-free survival [ Time Frame: 12 months ]
  2. Median overall survival [ Time Frame: 24 months ]
  3. Response rate according to RECIST 1.1 [ Time Frame: 24 months ]
  4. Treatment safety and tolerability according to NCI-CTCAE v.4.0 [ Time Frame: 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02056587


Locations
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Russian Federation
Tatarstan Regional Cancer Center
Kazan, Tatarstan, Russian Federation, 420029
Altai Regional Cancer Center
Barnaul, Russian Federation
N.N. Blokhin Russian Cancer Research Center
Moscow, Russian Federation, 115478
Sponsors and Collaborators
Kidney Cancer Research Bureau

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kidney Cancer Research Bureau
ClinicalTrials.gov Identifier: NCT02056587    
Other Study ID Numbers: CRAD001LRU02T
First Posted: February 6, 2014    Key Record Dates
Last Update Posted: February 6, 2014
Last Verified: February 2014
Keywords provided by Kidney Cancer Research Bureau:
renal cell carcinoma
kidney cancer
bevacizumab failure
everolimus
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sirolimus
Bevacizumab
Everolimus
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents