Trial Outcomes & Findings for Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma (NCT NCT01491672)
NCT ID: NCT01491672
Last Updated: 2016-06-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
134 participants
Primary outcome timeframe
20 months
Results posted on
2016-06-06
Participant Flow
This was an open-label study where all eligible participants were enrolled into one of 3 cohorts based upon prior first-line therapy.
Participant milestones
| Measure |
Prior Sunitinib
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
|---|---|---|---|
|
Overall Study
STARTED
|
58
|
62
|
14
|
|
Overall Study
Safety Set
|
58
|
61
|
14
|
|
Overall Study
COMPLETED
|
2
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
56
|
60
|
11
|
Reasons for withdrawal
| Measure |
Prior Sunitinib
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
4
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
7
|
0
|
|
Overall Study
Adverse Event
|
8
|
10
|
4
|
|
Overall Study
Disease progression
|
42
|
34
|
6
|
|
Overall Study
Protocol deviation
|
0
|
1
|
0
|
|
Overall Study
Death
|
0
|
4
|
0
|
Baseline Characteristics
Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Prior Sunitinib
n=58 Participants
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
Total
n=134 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
56.0 Years
STANDARD_DEVIATION 12.06 • n=5 Participants
|
56.5 Years
STANDARD_DEVIATION 11.14 • n=7 Participants
|
60.3 Years
STANDARD_DEVIATION 10.59 • n=5 Participants
|
56.7 Years
STANDARD_DEVIATION 11.48 • n=4 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
43 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
91 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 20 monthsPopulation: The full analysis set (FAS) was used. It included all enrolled 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.
Outcome measures
| Measure |
All Participants
n=134 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Progression-free Survival (PFS) - All Participants
|
7.4 months
Interval 5.6 to 10.5
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 20 monthsPopulation: The FAS was used. It included all enrolled participants.
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.
Outcome measures
| Measure |
All Participants
n=58 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Duration of PFS for Each First-line Treatment Cohort
|
5.6 months
Interval 3.7 to 11.3
|
7.8 months
Interval 5.7 to 11.0
|
12.9 months
Interval 2.6 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
—
|
SECONDARY outcome
Timeframe: 28 monthsPopulation: The FAS was used. It included all enrolled participants.
OS was defined as the time from date of enrollment to date of death due to any cause.
Outcome measures
| Measure |
All Participants
n=58 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
n=134 Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Overall Survival (OS)
|
23.8 months
Interval 13.7 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
17.2 months
Interval 11.9 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
NA months
Interval 15.9 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
23.8 months
Interval 17.0 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
SECONDARY outcome
Timeframe: 20 monthsPopulation: The FAS was used. It included all enrolled participants.
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.
Outcome measures
| Measure |
All Participants
n=58 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
n=134 Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Clinical Benefit Rate (CBR)
|
41 Participants
|
48 Participants
|
11 Participants
|
100 Participants
|
SECONDARY outcome
Timeframe: 20 monthsPopulation: The FAS was used. It included all enrolled participants.
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
Outcome measures
| Measure |
All Participants
n=58 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
n=134 Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Objective Response Rate (ORR)
|
4 Participants
|
3 Participants
|
3 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 20 monthsPopulation: 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.
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.
Outcome measures
| Measure |
All Participants
n=58 Participants
All participants received RAD001 10 mg daily.
|
Other Prior Vascular Endothelial Growth Factor (VEGF)
n=62 Participants
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 Participants
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
All Participants
n=134 Participants
All participants received RAD001 10 mg daily.
|
|---|---|---|---|---|
|
Duration of Response (DoR)
|
10.8 months
Interval 9.2 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
7.4 months
Interval 3.3 to 9.2
|
9.2 months
The lower and upper limits were not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
9.2 months
Interval 3.3 to
The upper limit was not estimable using the Kaplan Meier (KM) method as a result of too few events.
|
Adverse Events
Prior Sunitinib
Serious events: 13 serious events
Other events: 28 other events
Deaths: 0 deaths
Other Prior Anti VEGF
Serious events: 16 serious events
Other events: 33 other events
Deaths: 0 deaths
Prior Cytokines
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Prior Sunitinib
n=58 participants at risk
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
|
Other Prior Anti VEGF
n=61 participants at risk
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 participants at risk
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/58
|
3.3%
2/61
|
0.00%
0/14
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Gastrointestinal disorders
Abdominal pain
|
3.4%
2/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Gastrointestinal disorders
Constipation
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Gastrointestinal disorders
Gastritis
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
General disorders
Multi-organ failure
|
1.7%
1/58
|
3.3%
2/61
|
0.00%
0/14
|
|
General disorders
Sudden death
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Infections and infestations
Anal abscess
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Infections and infestations
Appendicitis
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Infections and infestations
Cellulitis
|
3.4%
2/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Infections and infestations
Necrotising fasciitis
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Infections and infestations
Perirectal abscess
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Infections and infestations
Pneumonia
|
3.4%
2/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Infections and infestations
Sepsis
|
3.4%
2/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Concussion
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Laceration
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Wound complication
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Investigations
X-ray with contrast upper gastrointestinal tract abnormal
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.7%
1/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Nervous system disorders
Cerebral haemorrhage
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Nervous system disorders
Hypertensive encephalopathy
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Nervous system disorders
Seizure
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Renal and urinary disorders
Acute kidney injury
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.7%
1/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Hydrothorax
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.7%
1/58
|
3.3%
2/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Pleural fibrosis
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.7%
1/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.7%
1/58
|
4.9%
3/61
|
0.00%
0/14
|
|
Vascular disorders
Hypertension
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Vascular disorders
Thrombosis
|
0.00%
0/58
|
1.6%
1/61
|
0.00%
0/14
|
Other adverse events
| Measure |
Prior Sunitinib
n=58 participants at risk
Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.
|
Other Prior Anti VEGF
n=61 participants at risk
Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.
|
Prior Cytokines
n=14 participants at risk
Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.8%
8/58
|
13.1%
8/61
|
28.6%
4/14
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/58
|
1.6%
1/61
|
7.1%
1/14
|
|
Gastrointestinal disorders
Diarrhoea
|
8.6%
5/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Gastrointestinal disorders
Mouth ulceration
|
3.4%
2/58
|
3.3%
2/61
|
7.1%
1/14
|
|
Gastrointestinal disorders
Stomatitis
|
8.6%
5/58
|
13.1%
8/61
|
35.7%
5/14
|
|
General disorders
Fatigue
|
0.00%
0/58
|
3.3%
2/61
|
7.1%
1/14
|
|
General disorders
General physical health deterioration
|
5.2%
3/58
|
1.6%
1/61
|
0.00%
0/14
|
|
General disorders
Pyrexia
|
3.4%
2/58
|
8.2%
5/61
|
7.1%
1/14
|
|
Infections and infestations
Localised infection
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Infections and infestations
Upper respiratory tract infection
|
5.2%
3/58
|
1.6%
1/61
|
0.00%
0/14
|
|
Investigations
Alanine aminotransferase increased
|
3.4%
2/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Investigations
Blood creatinine increased
|
1.7%
1/58
|
1.6%
1/61
|
7.1%
1/14
|
|
Investigations
Blood pressure increased
|
0.00%
0/58
|
1.6%
1/61
|
7.1%
1/14
|
|
Investigations
Blood uric acid increased
|
0.00%
0/58
|
1.6%
1/61
|
7.1%
1/14
|
|
Investigations
Hepatitis B DNA increased
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Investigations
Weight decreased
|
3.4%
2/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.2%
3/58
|
4.9%
3/61
|
14.3%
2/14
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.2%
3/58
|
8.2%
5/61
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
5.2%
3/58
|
6.6%
4/61
|
14.3%
2/14
|
|
Renal and urinary disorders
Proteinuria
|
6.9%
4/58
|
0.00%
0/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.4%
2/58
|
6.6%
4/61
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.7%
1/58
|
6.6%
4/61
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/58
|
0.00%
0/61
|
7.1%
1/14
|
|
Vascular disorders
Hypertension
|
3.4%
2/58
|
1.6%
1/61
|
7.1%
1/14
|
Additional Information
Study Director
Novartis
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER