Trial record 1 of 1 for:    NCT01491672
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Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (RECORD-4)

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: December 12, 2011
Last updated: October 5, 2015
Last verified: October 2015
This study will evaluate everolimus as second-line therapy in patients with metastatic renal cell carcinoma. Each patient will be enrolled 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.

Condition Intervention Phase
Metastatic Renal Cell Carcinoma
Drug: RAD001
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression-free survival in patients who receive everolimus as second-line treatment for metastatic renal cell carcinoma [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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.

Secondary Outcome Measures:
  • Safety profile of everolimus for the overall study population as well as for each first-line treatment cohort. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The time from date of enrollment to date of death due to any cause.

  • Clinical Benefit Rate (CBR) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

Enrollment: 135
Study Start Date: November 2011
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus
Drug: RAD001


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01491672

United States, New York
Memorial Sloan Kettering Cancer Center
NY, New York, United States, 90033
Novartis Investigative Site
Rio Negro, Viedma, Argentina, 8500
Novartis Investigative Site
Tucuman, Argentina, T4000
Novartis Investigative Site
Florianopolis, SC, Brazil, 88034-000
Novartis Investigative Site
Barretos, SP, Brazil, 14784-400
Novartis Investigative Site
São Paulo, SP, Brazil, 01246-000
Novartis Investigative Site
São Paulo, SP, Brazil, 01509-900
Novartis Investigative Site
Sofia, Bulgaria, 1784
China, Beijing
Novartis Investigative Site
Beijing, Beijing, China, 100730
China, Zhejiang
Novartis Investigative Site
Hangzhou, Zhejiang, China, 310003
Novartis Investigative Site
Beijing, China, 100021
Novartis Investigative Site
Guangzhou, China, 510060
Novartis Investigative Site
Shanghai, China, 200032
Russian Federation
Novartis Investigative Site
Leningrad Region, Russia, Russian Federation, 188663
Novartis Investigative Site
Moscow, Russia, Russian Federation, 125284
Novartis Investigative Site
Nizhny Novgorod, Russia, Russian Federation, 603001
Novartis Investigative Site
Obninsk, Russia, Russian Federation, 249036
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals Identifier: NCT01491672     History of Changes
Other Study ID Numbers: CRAD001L2404  2010-020447-13 
Study First Received: December 12, 2011
Last Updated: October 5, 2015
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: Associação Fundo de Incentivo à Pesquisa
Bulgaria: Ministry of Health
China: Food and Drug Administration
Denmark: Danish Medicines Agency

Keywords provided by Novartis:
Metastatic Renal Cell Carcinoma
Second Line

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Diseases
Kidney Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Physiological Effects of Drugs processed this record on May 26, 2016