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Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (RECORD-4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01491672
Recruitment Status : Completed
First Posted : December 14, 2011
Results First Posted : June 2, 2016
Last Update Posted : June 6, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 12, 2011
First Posted Date  ICMJE December 14, 2011
Results First Submitted Date  ICMJE April 26, 2016
Results First Posted Date  ICMJE June 2, 2016
Last Update Posted Date June 6, 2016
Study Start Date  ICMJE November 2011
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 2, 2016)
Progression-free Survival (PFS) - All Participants [ Time Frame: 20 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 13, 2011)
Progression-free survival in patients who receive everolimus as second-line treatment for metastatic renal cell carcinoma [ Time Frame: 24 months ]
To assess the duration of progression-free survival (PFS) during second-line treatment, 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 PFS will be based on the local radiological data according to the RECIST 1.0 Criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2016)
  • Duration of PFS for Each First-line Treatment Cohort [ Time Frame: 20 months ]
    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.
  • Overall Survival (OS) [ Time Frame: 28 months ]
    OS was defined as the time from date of enrollment to date of death due to any cause.
  • Clinical Benefit Rate (CBR) [ Time Frame: 20 months ]
    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.
  • Objective Response Rate (ORR) [ Time Frame: 20 months ]
    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
  • Duration of Response (DoR) [ Time Frame: 20 months ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2011)
  • Safety profile of everolimus for the overall study population as well as for each first-line treatment cohort. [ Time Frame: 24 months ]
    The assessment of safety will be based mainly on the frequency of adverse events and on the number of laboratory values that fall outside of pre-determined ranges.
  • Progression-free survival separately for each first-line treatment cohort [ Time Frame: 24 months ]
    Kaplan-Meier product-limit estimate of the PFS survival function as well as the median PFS along with it's 95% confidence interval will be displayed on the FAS separately for each first-line treatment cohort.
  • Overall survival [ Time Frame: 24 months ]
    The time from date of enrollment to date of death due to any cause.
  • Clinical Benefit Rate (CBR) [ Time Frame: 24 months ]
    The proportion of patients with best overall response of CR or PR or stable disease based on the local radiological data according to the RECIST 1.0 Criteria.
  • Objective Response Rate (ORR) [ Time Frame: 24 months ]
    The proportion of patients with best overall response of CR or PR based on the local radiological data according to the RECIST 1.0 Criteria
  • Duration of Response (DoR) [ Time Frame: 24 months ]
    The duration of response will also be calculated for each first-line treatment cohort, and is 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma
Official Title  ICMJE 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
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Renal Cell Carcinoma
Intervention  ICMJE Drug: RAD001
Study drug was supplied as 5 mg tablets in blister packs.
Other Name: Everolimus
Study Arms  ICMJE Experimental: RAD001
Participants, received RAD001 10 mg orally once daily.
Intervention: Drug: RAD001
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2016)
134
Original Estimated Enrollment  ICMJE
 (submitted: December 13, 2011)
201
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years old.
  2. 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.
  3. Patients must have had prior nephrectomy (partial or total).
  4. 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.
  5. Patients with a Karnofsky Performance Status ≥ 70%.
  6. Adequate bone marrow function as shown by:

    1. ANC ≥ 1.5 x 109/L,
    2. Platelets ≥ 100 x 109/L,
    3. Hemoglobin >9 g/dL
  7. Adequate liver function as shown by:

    1. Serum bilirubin ≤ 1.5 x ULN,
    2. ALT and AST ≤ 2.5 x ULN. Patients with known liver metastases may enroll if their AST and ALT ≤ 5 x ULN,
    3. INR < 1.3 (INR < 3 in patients treated with anticoagulants)
  8. Adequate renal function: serum creatinine ≤ 2.0 x ULN.
  9. Fasting serum cholesterol ≤300 mg/dl OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.
  10. Written informed consent obtained before any trial related activity and according to local guidelines.

Exclusion Criteria:

  1. Patients with brain metastases.
  2. 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.

  3. Patients in anticipation of the need for major surgical procedure during the course of the study.
  4. 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).
  5. Patients with a serious non-healing wound, ulcer, or bone fracture.
  6. Patients with a history of seizure(s) not controlled with standard medical therapy.
  7. Patients who have received more than one prior treatment regimen for metastatic renalcell carcinoma
  8. Patients who have received adjuvant therapy for RCC
  9. Patients who have previously received systemic mTOR inhibitors (eg, sirolimus, temsirolimus, everolimus)
  10. Patients with a known hypersensitivity to everolimus or other rapamycins (eg, sirolimus, temsirolimus) or to its excipients.
  11. History or clinical evidence of central nervous system (CNS) metastases.
  12. Clinically significant gastrointestinal abnormalities including, but not limited to:

    1. Malabsorption syndrome:
    2. Major resection of the stomach or small bowel that could affect the absorption of study drug
    3. Active peptic ulcer disease
    4. Inflammatory bowel disease:

    i. 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.

  13. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
  14. Active bleeding diathesis
  15. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 2.0 x ULN.
  16. Patients who have any severe and/or uncontrolled medical conditions such as:

    1. unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction

      ≤ 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia,

    2. active or uncontrolled severe infection,
    3. history of invasive fungal infections,
    4. severe hepatic impairment (Child-Pugh class C),
    5. severely impaired lung function
  17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) ≤ 6 months before start of study treatment.
  18. 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.
  19. 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).
  20. Female patients who are pregnant or nursing (lactating).
  21. 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.

  22. 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.
  23. Patients unwilling or unable to comply with the protocol.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   China,   Russian Federation,   United States
Removed Location Countries Denmark
 
Administrative Information
NCT Number  ICMJE NCT01491672
Other Study ID Numbers  ICMJE CRAD001L2404
2010-020447-13 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP