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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 )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Renal Cell Carcinoma
Intervention Drug: RAD001
Enrollment 134
Recruitment Details This was an open-label study where all eligible participants were enrolled into one of 3 cohorts based upon prior first-line therapy.
Pre-assignment Details  
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines
Hide Arm/Group Description Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily. Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily. Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
Period Title: Overall Study
Started 58 62 [1] 14
Safety Set 58 61 14
Completed 2 2 3
Not Completed 56 60 11
Reason Not Completed
Lost to Follow-up             0             4             1
Withdrawal by Subject             6             7             0
Adverse Event             8             10             4
Disease progression             42             34             6
Protocol deviation             0             1             0
Death             0             4             0
[1]
1 participant died prior to treatment initiation.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines Total
Hide Arm/Group Description Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily. Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily. Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily. Total of all reporting groups
Overall Number of Baseline Participants 58 62 14 134
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 58 participants 62 participants 14 participants 134 participants
56.0  (12.06) 56.5  (11.14) 60.3  (10.59) 56.7  (11.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 58 participants 62 participants 14 participants 134 participants
Female
15
  25.9%
22
  35.5%
6
  42.9%
43
  32.1%
Male
43
  74.1%
40
  64.5%
8
  57.1%
91
  67.9%
1.Primary Outcome
Title Progression-free Survival (PFS) - All Participants
Hide Description 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.
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) was used. It included all enrolled participants.
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants received RAD001 10 mg daily.
Overall Number of Participants Analyzed 134
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(5.6 to 10.5)
2.Secondary Outcome
Title Duration of PFS for Each First-line Treatment Cohort
Hide Description 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.
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was used. It included all enrolled participants.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines
Hide Arm/Group Description:
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
Overall Number of Participants Analyzed 58 62 14
Median (95% Confidence Interval)
Unit of Measure: months
5.6
(3.7 to 11.3)
7.8
(5.7 to 11.0)
12.9 [1] 
(2.6 to NA)
[1]
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from date of enrollment to date of death due to any cause.
Time Frame 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was used. It included all enrolled participants.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines All Participants
Hide Arm/Group Description:
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All participants received RAD001 10 mg daily.
Overall Number of Participants Analyzed 58 62 14 134
Median (95% Confidence Interval)
Unit of Measure: months
23.8 [1] 
(13.7 to NA)
17.2 [1] 
(11.9 to NA)
NA [1] 
(15.9 to NA)
23.8 [1] 
(17.0 to NA)
[1]
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
4.Secondary Outcome
Title Clinical Benefit Rate (CBR)
Hide Description 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.
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was used. It included all enrolled participants.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines All Participants
Hide Arm/Group Description:
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All participants received RAD001 10 mg daily.
Overall Number of Participants Analyzed 58 62 14 134
Measure Type: Number
Unit of Measure: Participants
41 48 11 100
5.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description 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
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was used. It included all enrolled participants.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines All Participants
Hide Arm/Group Description:
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All participants received RAD001 10 mg daily.
Overall Number of Participants Analyzed 58 62 14 134
Measure Type: Number
Unit of Measure: Participants
4 3 3 10
6.Secondary Outcome
Title Duration of Response (DoR)
Hide Description 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.
Time Frame 20 months
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS was considered for this analysis. The FAS included all enrolled participants. Only participants who achieved a CR or PR were analyzed. Therefore, actual n=4,3,3,10.
Arm/Group Title Prior Sunitinib Other Prior Vascular Endothelial Growth Factor (VEGF) Prior Cytokines All Participants
Hide Arm/Group Description:
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All participants received RAD001 10 mg daily.
Overall Number of Participants Analyzed 58 62 14 134
Median (95% Confidence Interval)
Unit of Measure: months
10.8 [1] 
(9.2 to NA)
7.4
(3.3 to 9.2)
9.2 [2] 
(NA to NA)
9.2 [1] 
(3.3 to NA)
[1]
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
[2]
The lower and upper limits were not estimable using the Kaplan Meier (KM) method as a result of too few events.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Prior Sunitinib Other Prior Anti VEGF Prior Cytokines
Hide Arm/Group Description Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily. Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily. Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All-Cause Mortality
Prior Sunitinib Other Prior Anti VEGF Prior Cytokines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Prior Sunitinib Other Prior Anti VEGF Prior Cytokines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/58 (22.41%)   16/61 (26.23%)   3/14 (21.43%) 
Blood and lymphatic system disorders       
Anaemia  1  0/58 (0.00%)  2/61 (3.28%)  0/14 (0.00%) 
Cardiac disorders       
Cardiac failure  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Cardiac failure congestive  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  2/58 (3.45%)  0/61 (0.00%)  0/14 (0.00%) 
Constipation  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Gastritis  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Gastrointestinal haemorrhage  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
General disorders       
Multi-organ failure  1  1/58 (1.72%)  2/61 (3.28%)  0/14 (0.00%) 
Sudden death  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Infections and infestations       
Anal abscess  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Appendicitis  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Cellulitis  1  2/58 (3.45%)  0/61 (0.00%)  0/14 (0.00%) 
Lobar pneumonia  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Necrotising fasciitis  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Perirectal abscess  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Pneumonia  1  2/58 (3.45%)  0/61 (0.00%)  0/14 (0.00%) 
Sepsis  1  2/58 (3.45%)  1/61 (1.64%)  0/14 (0.00%) 
Injury, poisoning and procedural complications       
Concussion  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Femur fracture  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Laceration  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Lower limb fracture  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Lumbar vertebral fracture  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Wound complication  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Investigations       
X-ray with contrast upper gastrointestinal tract abnormal  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/58 (1.72%)  1/61 (1.64%)  0/14 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Pathological fracture  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Renal neoplasm  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Nervous system disorders       
Cerebral haemorrhage  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Hypertensive encephalopathy  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Seizure  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Psychiatric disorders       
Disorientation  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  1/58 (1.72%)  1/61 (1.64%)  0/14 (0.00%) 
Hydrothorax  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Interstitial lung disease  1  1/58 (1.72%)  2/61 (3.28%)  0/14 (0.00%) 
Pleural effusion  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Pleural fibrosis  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Pulmonary embolism  1  1/58 (1.72%)  0/61 (0.00%)  0/14 (0.00%) 
Respiratory failure  1  1/58 (1.72%)  3/61 (4.92%)  0/14 (0.00%) 
Vascular disorders       
Hypertension  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Thrombosis  1  0/58 (0.00%)  1/61 (1.64%)  0/14 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Prior Sunitinib Other Prior Anti VEGF Prior Cytokines
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/58 (48.28%)   33/61 (54.10%)   12/14 (85.71%) 
Blood and lymphatic system disorders       
Anaemia  1  8/58 (13.79%)  8/61 (13.11%)  4/14 (28.57%) 
Iron deficiency anaemia  1  0/58 (0.00%)  1/61 (1.64%)  1/14 (7.14%) 
Gastrointestinal disorders       
Diarrhoea  1  5/58 (8.62%)  1/61 (1.64%)  0/14 (0.00%) 
Mouth ulceration  1  2/58 (3.45%)  2/61 (3.28%)  1/14 (7.14%) 
Stomatitis  1  5/58 (8.62%)  8/61 (13.11%)  5/14 (35.71%) 
General disorders       
Fatigue  1  0/58 (0.00%)  2/61 (3.28%)  1/14 (7.14%) 
General physical health deterioration  1  3/58 (5.17%)  1/61 (1.64%)  0/14 (0.00%) 
Pyrexia  1  2/58 (3.45%)  5/61 (8.20%)  1/14 (7.14%) 
Infections and infestations       
Localised infection  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Tonsillitis  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Upper respiratory tract infection  1  3/58 (5.17%)  1/61 (1.64%)  0/14 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  2/58 (3.45%)  0/61 (0.00%)  1/14 (7.14%) 
Blood creatinine increased  1  1/58 (1.72%)  1/61 (1.64%)  1/14 (7.14%) 
Blood pressure increased  1  0/58 (0.00%)  1/61 (1.64%)  1/14 (7.14%) 
Blood uric acid increased  1  0/58 (0.00%)  1/61 (1.64%)  1/14 (7.14%) 
Hepatitis B DNA increased  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Lymphocyte count decreased  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Weight decreased  1  2/58 (3.45%)  0/61 (0.00%)  1/14 (7.14%) 
Metabolism and nutrition disorders       
Diabetes mellitus  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Hypercholesterolaemia  1  3/58 (5.17%)  3/61 (4.92%)  2/14 (14.29%) 
Hyperglycaemia  1  3/58 (5.17%)  5/61 (8.20%)  1/14 (7.14%) 
Hypertriglyceridaemia  1  3/58 (5.17%)  4/61 (6.56%)  2/14 (14.29%) 
Renal and urinary disorders       
Proteinuria  1  4/58 (6.90%)  0/61 (0.00%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  2/58 (3.45%)  4/61 (6.56%)  0/14 (0.00%) 
Oropharyngeal pain  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Pneumonitis  1  1/58 (1.72%)  4/61 (6.56%)  1/14 (7.14%) 
Pneumothorax  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Skin and subcutaneous tissue disorders       
Dry skin  1  0/58 (0.00%)  0/61 (0.00%)  1/14 (7.14%) 
Vascular disorders       
Hypertension  1  2/58 (3.45%)  1/61 (1.64%)  1/14 (7.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01491672    
Other Study ID Numbers: CRAD001L2404
2010-020447-13 ( EudraCT Number )
First Submitted: December 12, 2011
First Posted: December 14, 2011
Results First Submitted: April 26, 2016
Results First Posted: June 2, 2016
Last Update Posted: June 6, 2016