Trial Outcomes & Findings for Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC (NCT NCT01379521)
NCT ID: NCT01379521
Last Updated: 2017-05-03
Results Overview
Time to Progression (TTP) defined as the time from the date of randomization to the date of first documented radiological confirmation of disease progression based on modified RECIST criteria. Progressive Disease: \>20% increase in sum of the longest diameters (SLD) of "viable" target lesion (arterial phase enhancement)
TERMINATED
PHASE2
65 participants
3, 6, 12, 18 and 24 months
2017-05-03
Participant Flow
Of the 65 patients who were screened they reflect the actual enrolment but 59 patients were randomized and were included in the FAS, the Safety Set and the PP Set. There were no exclusions. Post-Treatment evaluations included any patients that was treated and does not reflect the number completed in the Overall Study.
Participant milestones
| Measure |
Everolimus + TACE
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Overall Study -Treatment Period
STARTED
|
33
|
26
|
|
Overall Study -Treatment Period
COMPLETED
|
0
|
0
|
|
Overall Study -Treatment Period
NOT COMPLETED
|
33
|
26
|
|
Post-Treatment Evaluations
STARTED
|
25
|
21
|
|
Post-Treatment Evaluations
COMPLETED
|
0
|
0
|
|
Post-Treatment Evaluations
NOT COMPLETED
|
25
|
21
|
Reasons for withdrawal
| Measure |
Everolimus + TACE
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Overall Study -Treatment Period
Adverse Event
|
3
|
0
|
|
Overall Study -Treatment Period
Abnormal test procedure results
|
0
|
1
|
|
Overall Study -Treatment Period
Disease Progression
|
23
|
22
|
|
Overall Study -Treatment Period
New Cancer Therapy
|
1
|
0
|
|
Overall Study -Treatment Period
Protocol Deviation
|
0
|
2
|
|
Overall Study -Treatment Period
Withdrawal by Subject
|
3
|
0
|
|
Overall Study -Treatment Period
Administrative Problems
|
1
|
0
|
|
Overall Study -Treatment Period
Death
|
2
|
1
|
|
Post-Treatment Evaluations
Disease Progression
|
22
|
20
|
|
Post-Treatment Evaluations
Withdrawal by Subject
|
2
|
1
|
|
Post-Treatment Evaluations
Death
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of RAD001 + TACE in Localized Unresectable HCC
Baseline characteristics by cohort
| Measure |
Everolimus + TACE
n=33 Participants
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=26 Participants
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
Total
n=59 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.5 years
STANDARD_DEVIATION 11.29 • n=5 Participants
|
61.0 years
STANDARD_DEVIATION 10.32 • n=7 Participants
|
59.6 years
STANDARD_DEVIATION 10.85 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3, 6, 12, 18 and 24 monthsPopulation: Full Analysis Set (FAS) comprises all randomized patients.
Time to Progression (TTP) defined as the time from the date of randomization to the date of first documented radiological confirmation of disease progression based on modified RECIST criteria. Progressive Disease: \>20% increase in sum of the longest diameters (SLD) of "viable" target lesion (arterial phase enhancement)
Outcome measures
| Measure |
Everolimus + TACE
n=33 Participants
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=26 Participants
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Time to Progression (TTP) Based on the Modified RECIST Criteria
|
6.3 months
Interval 4.3 to 6.6
|
6.4 months
Interval 4.0 to 8.9
|
SECONDARY outcome
Timeframe: 6, 12 months, end of studyPopulation: Full Analysis Set (FAS) comprises all randomized patients. The trial results are inconclusive as the study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Overall response rate was defined as the number of patients whose best overall response was either complete response or partial response according to the modified RECIST. Complete response: Disappearance of arterial phase enhance-ment in all target lesions. Partial response: \>30% decrease in sum of the longest diameters (SLD) of "viable" target lesion (arterial phase enhance-ment)Disease control rate was defined as the number of patients with a best overall response of complete response, partial response or stable disease. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6, 12 months, end of studyPopulation: Full Analysis Set (FAS) comprises all randomized patients. The trial results are inconclusive as the study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Time to Progression (TTP) defined as the time from the date of randomization to the date of first documented radiological confirmation of disease progression based on original RECIST criteria. Progressive Disease: \>20% increase in sum of the longest diameters (SLD) of target lesions with an absolute increase of ≥5 mm; new lesions. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6, 12 months, end of studyPopulation: Full Analysis Set (FAS) comprises all randomized patients. The trial results are inconclusive as the study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Overall response rate was defined as the number of patients whose best overall response was either complete response or partial response according to the Complete response: Disappearance of all target lesions or lymph nodes \<10 mm in the short axis Partial response: \>30% decrease in sum of the longest diameters (SLD) of target lesions Disease control rate was defined as the number of patients with a best overall response of complete response, partial response or stable disease. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 6, 12, 18, 24, 30 monthsPopulation: Full Analysis Set (FAS) comprises all randomized patients. The trial results are inconclusive as the study was underpowered
Overall survival was defined as the time from date of randomization to date of death due to any cause. If death had not occurred at the date of the analysis cut-off then OS was censored at the date of the last contact.
Outcome measures
| Measure |
Everolimus + TACE
n=33 Participants
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=26 Participants
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Overall Survival (OS)
|
29.9 months
Interval 12.0 to
The trial results are inconclusive as study was underpowered therefore upper limit was not calculated due to not enough events.
|
21.7 months
Interval 19.4 to 27.9
|
SECONDARY outcome
Timeframe: 30 monthsPopulation: Full Analysis Set (FAS) comprises all randomized patients. The trial results are inconclusive as the study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Incidences of cumulative new nodular recurrence, portal vein invasion and extra hepatic metastases but incidence of portal vein invasion meant those patients without documented vascular invasion at screening/baseline. The study was terminated early due to slow enrollment of 4 years, higher than anticipated screen failure rate due to a higher than anticipated proportion of patients having advanced liver disease and a change in clinical practice the total of 80 patients was not reached with only 59 patients recruited in total. The study was underpowered due to termination therefore data was not collected and the outcome measure was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: baseline, 30 monthsPopulation: Full Analysis Set (FAS) comprises all randomized patients.
Percentage of participants with a decrease in the sum of the of longest diameters (SLD) of target lesions from Baseline to 30 months
Outcome measures
| Measure |
Everolimus + TACE
n=32 Participants
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=25 Participants
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Percentage of Participants With a Decrease in the Sum of the of Longest Diameters (SLD) of Target Lesions From Baseline to 30 Months
|
93.8 Percentage of participants
|
88.0 Percentage of participants
|
Adverse Events
Everolimus + TACE
Placebo + TACE
Serious adverse events
| Measure |
Everolimus + TACE
n=33 participants at risk
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=26 participants at risk
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
3.0%
1/33
|
0.00%
0/26
|
|
Cardiac disorders
Cardiac failure congestive
|
3.0%
1/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/33
|
3.8%
1/26
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.00%
0/33
|
3.8%
1/26
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
3.0%
1/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
3.0%
1/33
|
0.00%
0/26
|
|
General disorders
Multi-organ failure
|
3.0%
1/33
|
0.00%
0/26
|
|
General disorders
Pyrexia
|
6.1%
2/33
|
0.00%
0/26
|
|
Infections and infestations
Liver abscess
|
3.0%
1/33
|
3.8%
1/26
|
|
Infections and infestations
Peritonitis bacterial
|
0.00%
0/33
|
3.8%
1/26
|
|
Infections and infestations
Pneumonia
|
3.0%
1/33
|
3.8%
1/26
|
|
Infections and infestations
Sepsis
|
0.00%
0/33
|
3.8%
1/26
|
|
Infections and infestations
Septic shock
|
3.0%
1/33
|
0.00%
0/26
|
|
Injury, poisoning and procedural complications
Post embolisation syndrome
|
3.0%
1/33
|
0.00%
0/26
|
|
Injury, poisoning and procedural complications
Renal haematoma
|
3.0%
1/33
|
0.00%
0/26
|
|
Investigations
Hepatic enzyme increased
|
3.0%
1/33
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.0%
1/33
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
3.0%
1/33
|
0.00%
0/26
|
|
Renal and urinary disorders
Renal failure acute
|
3.0%
1/33
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
3.0%
1/33
|
0.00%
0/26
|
|
Vascular disorders
Hypertension
|
3.0%
1/33
|
0.00%
0/26
|
|
Vascular disorders
Hypotension
|
0.00%
0/33
|
3.8%
1/26
|
|
Vascular disorders
Hypovolaemic shock
|
0.00%
0/33
|
3.8%
1/26
|
Other adverse events
| Measure |
Everolimus + TACE
n=33 participants at risk
everolimus 7.5mg/day by mouth + transcatheter arterial chemoembolization (TACE)
|
Placebo + TACE
n=26 participants at risk
Placebo by mouth + transcatheter arterial chemoembolization (TACE)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.2%
6/33
|
11.5%
3/26
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
18.2%
6/33
|
3.8%
1/26
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/33
|
7.7%
2/26
|
|
Gastrointestinal disorders
Abdominal pain
|
57.6%
19/33
|
65.4%
17/26
|
|
Gastrointestinal disorders
Abdominal pain upper
|
24.2%
8/33
|
19.2%
5/26
|
|
Gastrointestinal disorders
Ascites
|
15.2%
5/33
|
7.7%
2/26
|
|
Gastrointestinal disorders
Constipation
|
18.2%
6/33
|
30.8%
8/26
|
|
Gastrointestinal disorders
Diarrhoea
|
12.1%
4/33
|
7.7%
2/26
|
|
Gastrointestinal disorders
Gastritis
|
6.1%
2/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Gingival bleeding
|
6.1%
2/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Irritable bowel syndrome
|
6.1%
2/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Mouth ulceration
|
27.3%
9/33
|
7.7%
2/26
|
|
Gastrointestinal disorders
Nausea
|
18.2%
6/33
|
19.2%
5/26
|
|
Gastrointestinal disorders
Stomatitis
|
21.2%
7/33
|
0.00%
0/26
|
|
Gastrointestinal disorders
Vomiting
|
21.2%
7/33
|
23.1%
6/26
|
|
General disorders
Mucosal inflammation
|
6.1%
2/33
|
0.00%
0/26
|
|
General disorders
Oedema peripheral
|
15.2%
5/33
|
0.00%
0/26
|
|
General disorders
Pyrexia
|
36.4%
12/33
|
46.2%
12/26
|
|
Infections and infestations
Hepatitis b
|
6.1%
2/33
|
0.00%
0/26
|
|
Infections and infestations
Herpes zoster
|
9.1%
3/33
|
0.00%
0/26
|
|
Infections and infestations
Nasopharyngitis
|
6.1%
2/33
|
0.00%
0/26
|
|
Infections and infestations
Pneumonia
|
6.1%
2/33
|
0.00%
0/26
|
|
Infections and infestations
Skin infection
|
6.1%
2/33
|
0.00%
0/26
|
|
Infections and infestations
Upper respiratory tract infection
|
6.1%
2/33
|
0.00%
0/26
|
|
Investigations
Alanine aminotransferase increased
|
6.1%
2/33
|
3.8%
1/26
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
3/33
|
3.8%
1/26
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/33
|
7.7%
2/26
|
|
Investigations
Platelet count decreased
|
9.1%
3/33
|
3.8%
1/26
|
|
Investigations
Weight decreased
|
9.1%
3/33
|
7.7%
2/26
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
11/33
|
19.2%
5/26
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
9.1%
3/33
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
12.1%
4/33
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.1%
2/33
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.2%
5/33
|
3.8%
1/26
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
6.1%
2/33
|
0.00%
0/26
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.1%
2/33
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.1%
4/33
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
6.1%
2/33
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
12.1%
4/33
|
7.7%
2/26
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/33
|
7.7%
2/26
|
|
Nervous system disorders
Dizziness
|
6.1%
2/33
|
0.00%
0/26
|
|
Nervous system disorders
Headache
|
12.1%
4/33
|
7.7%
2/26
|
|
Psychiatric disorders
Insomnia
|
21.2%
7/33
|
19.2%
5/26
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
6.1%
2/33
|
3.8%
1/26
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
18.2%
6/33
|
23.1%
6/26
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.1%
4/33
|
0.00%
0/26
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.0%
1/33
|
11.5%
3/26
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.1%
2/33
|
7.7%
2/26
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.1%
4/33
|
0.00%
0/26
|
|
Vascular disorders
Hypertension
|
12.1%
4/33
|
3.8%
1/26
|
Additional Information
Study Director
Novartis Pharmaceuticals
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