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Metastatic Renal Cell CarcinomaPhase 2RECORD-4NCT01491672

Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma

A Phase 2 study testing RAD001 in people with Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 17 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will evaluate everolimus as second-line therapy in patients with metastatic renal cell carcinoma. Each patient will be enrolled and stratified in one of three cohorts based upon their first-line therapy: 1) prior cytokines, 2) prior sunitinib, or 3) prior anti-VEGF therapy other than sunitinib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Renal Cell Carcinoma
What is being tested?
RAD001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
134 participants
Where
17 sitesin 6 countries
Study dates
Nov 2011to May 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years old.
  • Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell (or with a component of clear cell) renal carcinoma that have previously progressed on or were intolerant to first-line therapy with sunitinib, sorafenib, pazopanib, axitinib, bevacizumab, or cytokine therapy.
  • Patients must have had prior nephrectomy (partial or total).
  • Patients with at least one measurable lesion at baseline as per the RECIST 1.0 criteria. If skin lesions are reported as target lesions, they should be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph.
  • Patients with a Karnofsky Performance Status ≥ 70%.
  • Adequate bone marrow function as shown by:
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  • ANC ≥ 1.5 x 109/L,
  • Platelets ≥ 100 x 109/L,
  • Hemoglobin >9 g/dL
  • Adequate liver function as shown by:
  • Serum bilirubin ≤ 1.5 x ULN,
  • ALT and AST ≤ 2.5 x ULN. Patients with known liver metastases may enroll if their AST and ALT ≤ 5 x ULN,
  • INR < 1.3 (INR < 3 in patients treated with anticoagulants)
  • Adequate renal function: serum creatinine ≤ 2.0 x ULN.
  • Fasting serum cholesterol ≤300 mg/dl OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.
  • Written informed consent obtained before any trial related activity and according to local guidelines.

Who cannot join

  • Patients with brain metastases.
  • Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal or intrapelvic), open biopsy, or significant traumatic injury to avoid wound healing complications.
  • Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry.
  • Patients in anticipation of the need for major surgical procedure during the course of the study.
  • Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).
  • Patients with a serious non-healing wound, ulcer, or bone fracture.
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  • Patients with a history of seizure(s) not controlled with standard medical therapy.
  • Patients who have received more than one prior treatment regimen for metastatic renalcell carcinoma
  • Patients who have received adjuvant therapy for RCC
  • Patients who have previously received systemic mTOR inhibitors (eg, sirolimus, temsirolimus, everolimus)
  • Patients with a known hypersensitivity to everolimus or other rapamycins (eg, sirolimus, temsirolimus) or to its excipients.
  • History or clinical evidence of central nervous system (CNS) metastases.
  • Clinically significant gastrointestinal abnormalities including, but not limited to:
  • Malabsorption syndrome:
  • Major resection of the stomach or small bowel that could affect the absorption of study drug
  • Active peptic ulcer disease
  • Inflammatory bowel disease:
  • Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation ii. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
  • Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
  • Active bleeding diathesis
  • Uncontrolled diabetes mellitus as defined by fasting serum glucose > 2.0 x ULN.
  • Patients who have any severe and/or uncontrolled medical conditions such as:
  • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction
  • ≤ 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia,
  • active or uncontrolled severe infection,
  • history of invasive fungal infections,
  • severe hepatic impairment (Child-Pugh class C),
  • severely impaired lung function
  • History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) ≤ 6 months before start of study treatment.
  • History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
  • Patients who have a history of another primary malignancy and off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix or breast, and localized cancer of the bladder (T1) and prostate (T1 - T2).
  • Female patients who are pregnant or nursing (lactating).
  • Adults of reproductive potential who are not using effective birth control methods.
  • Adequate contraceptives must be used throughout the trial and for 8 weeks after last study drug administration in female patients. Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first administration of study drug.
  • Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start. This should not include sunitinib, sorafenib, axitinib, pazopanib and cytokines.
  • Patients unwilling or unable to comply with the protocol.

Trial locations and contacts

17 sites in 6 countries.

17 sites in 6 countries

China5 sites

  • Novartis Investigative Site

    Beijing, Beijing Municipality, 100730

  • Novartis Investigative Site

    Beijing, 100021

  • Novartis Investigative Site

    Guangzhou, 510060

  • Novartis Investigative Site

    Hangzhou, Zhejiang, 310003

  • Novartis Investigative Site

    Shanghai, 200032

Other trials in China

Brazil4 sites

  • Novartis Investigative Site

    Barretos, São Paulo, 14784-400

  • Novartis Investigative Site

    Florianópolis, Santa Catarina, 88034-000

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246-000

  • Novartis Investigative Site

    São Paulo, São Paulo, 01509-900

Other trials in Brazil

Russia4 sites

  • Novartis Investigative Site

    Leningrad Region, Russia, 188663

  • Novartis Investigative Site

    Moscow, Russia, 125284

  • Novartis Investigative Site

    Nizhny Novgorod, Russia, 603001

  • Novartis Investigative Site

    Obninsk, Russia, 249036

Other trials in Russia

Argentina2 sites

  • Novartis Investigative Site

    Rio Negro, Viedma, 8500

  • Novartis Investigative Site

    San Miguel de Tucumán, Tucumán Province, T4000

Other trials in Argentina

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 90033

Other trials in United States

Bulgaria1 site

  • Novartis Investigative Site

    Sofia, 1784

Other trials in Bulgaria

About this study

Official title: An Open-label, Multicenter Phase II Study to Examine the Efficacy and Safety of Everolimus as Second-line Therapy in the Treatment of Patients With Metastatic Renal Cell Carcinoma

This study will evaluate everolimus as second-line therapy in patients with metastatic renal cell carcinoma. Each patient will be enrolled and stratified in one of three cohorts based upon their first-line therapy: 1) prior cytokines, 2) prior sunitinib, or 3) prior anti-VEGF therapy other than sunitinib.

Being tested
RAD001
Keywords
Metastatic Renal Cell Carcinoma, Second Line, Everolimus, RAD001
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAD001Drug

    Also called Everolimus

    Study drug was supplied as 5 mg tablets in blister packs.

Study groups in NCT01491672
Study groupRoleWhat they receive
RAD001ExperimentalParticipants, received RAD001 10 mg orally once daily.
Receives: Drug: RAD001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) - All Participants

    PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. The primary analysis of PFS was based on a local radiology review of CT scans and MRI collected until the participant experienced disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.

    Measured: 20 months

Secondary outcomes (5)

  1. Duration of PFS for Each First-line Treatment Cohort

    Duration of PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. Participants' assessment was based on the local radiological data according to the RECIST 1.0 Criteria.

    Measured: 20 months

  2. Overall Survival (OS)

    OS was defined as the time from date of enrollment to date of death due to any cause.

    Measured: 28 months

  3. Clinical Benefit Rate (CBR)

    CBR was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease based on the local radiological data according to the RECIST 1.0 criteria.

    Measured: 20 months

  4. Objective Response Rate (ORR)

    ORR was defined as the proportion of participants with best overall response of CR or PR based on the local radiological data according to the RECIST 1.0 Criteria

    Measured: 20 months

  5. Duration of Response (DoR)

    DoR was defined as the time from the first occurrence of PR or CR (as per local radiological review) until the date of the first documented disease progression or death due to underlying cancer.

    Measured: 20 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionMay 2015
  4. Study completionMay 2015

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01491672
Sponsor's protocol ID
CRAD001L2404
Other IDs
2010-020447-13
Acronym
RECORD-4
Status last verified
Jun 2016
First submitted
12 Dec 2011
Last updated
6 Jun 2016
Data monitoring committee
No

Publications

  • Yang L, Alyasova A, Ye D, Ridolfi A, Dezzani L, Motzer RJ. RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis. BMC Cancer. 2018 Feb 17;18(1):195. doi: 10.1186/s12885-018-4091-5.

    PubMed 29454306

  • Motzer RJ, Alyasova A, Ye D, Karpenko A, Li H, Alekseev B, Xie L, Kurteva G, Kowalyszyn R, Karyakin O, Neron Y, Cosgriff T, Collins L, Brechenmacher T, Lin C, Morgan L, Yang L. Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4). Ann Oncol. 2016 Mar;27(3):441-8. doi: 10.1093/annonc/mdv612. Epub 2015 Dec 17.

    PubMed 26681676

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RAD001 in people with Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 17 sites in 6 countries.

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 16 inclusion and 36 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 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in China, Brazil, Russia, Argentina, United States and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression-free Survival (PFS) - All Participants (time frame: 20 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 NCT01491672, which also lists 2 linked publications.

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 Jun 2016.

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