Metastatic Renal Cell CarcinomaPhase 4NCT02056587
Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
A Phase 4 study testing Everolimus in people with Metastatic Renal Cell Carcinoma, run by Kidney Cancer Research Bureau at 3 sites in Russia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- Everolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 3 sitesRussia
- Study dates
- Nov 2011to Oct 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Russia3 sites
Altai Regional Cancer Center
Barnaul
Tatarstan Regional Cancer Center
Kazan', Tatarstan Republic, 420029
N.N. Blokhin Russian Cancer Research Center
Moscow, 115478
About this study
Official title: Everolimus (Afinitor) in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
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.
Read the 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
- Conditions
- Metastatic Renal Cell Carcinoma
- Being tested
- Everolimus
- Keywords
- renal cell carcinoma, kidney cancer, bevacizumab failure, everolimus
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | 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. Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study)
Measured: 2 months
Secondary outcomes (4)
Median progression-free survival
Measured: 12 months
Median overall survival
Measured: 24 months
Response rate according to RECIST 1.1
Measured: 24 months
Treatment safety and tolerability according to NCI-CTCAE v.4.0
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2014 (estimated)
- Study startNov 2011
- Primary completionApr 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kidney Cancer Research Bureau
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02056587
- Sponsor's protocol ID
- CRAD001LRU02T
- Status last verified
- Feb 2014
- First submitted
- 4 Feb 2014
- Last updated
- 6 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 25466382
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Everolimus (Afinitor) in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
- ClinicalTrials.gov ID
- NCT02056587
- Acronym / sponsor ID
- CRAD001LRU02T
- Conditions
- Metastatic Renal Cell Carcinoma
- Keywords
- renal cell carcinoma, kidney cancer, bevacizumab failure, everolimus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Kidney Cancer Research BureauUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 6 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: EverolimusAll 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically proven renal cell carcinoma
- CT-confirmed measurable disease
- Disease progression after bevacizumab +/- IFN
- Favorable/intermediate prognosis according to MSKCC
- Nephrectomy
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAll 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 |
Primary outcome
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study)
Time frame: 2 months
4 secondary outcomes
Median progression-free survival
Time frame: 12 months
Median overall survival
Time frame: 24 months
Response rate according to RECIST 1.1
Time frame: 24 months
Treatment safety and tolerability according to NCI-CTCAE v.4.0
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2014.
- Derived from this study: PubMed 25466382Tsimafeyeu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Everolimus in people with Metastatic Renal Cell Carcinoma, run by Kidney Cancer Research Bureau at 3 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint is the proportion of progression-free patients for 2 months (based on results of a phase III study) (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02056587, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2014.