Trial Outcomes & Findings for Sequentiality of Everolimus and STZ-5FU in Advanced Pancreatic Neuroendocrine Tumor (NCT NCT02246127)
NCT ID: NCT02246127
Last Updated: 2025-05-11
Results Overview
Proportion of patients who are alive without progression to Course 1 from the date of randomization in STZ based CT vs Everolimus arms Definitions for PFS rate for course 1 at 12 months: * No: number (proportion) of patients who were not alive and progression free according to the respective definition (main, conservative, and optimistic); * Yes: number (proportion) of patients who were alive and progression free according to the respective definition (main, conservative, and optimistic).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
141 participants
Primary outcome timeframe
At 12 months
Results posted on
2025-05-11
Participant Flow
Participant milestones
| Measure |
Sequence A, Drug: Everolimus First
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
First Course Treatment
STARTED
|
72
|
69
|
|
First Course Treatment
COMPLETED
|
36
|
33
|
|
First Course Treatment
NOT COMPLETED
|
36
|
36
|
|
Second Course Treatment
STARTED
|
36
|
33
|
|
Second Course Treatment
COMPLETED
|
36
|
33
|
|
Second Course Treatment
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Sequence A, Drug: Everolimus First
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
First Course Treatment
Adverse Event
|
9
|
7
|
|
First Course Treatment
Withdrawal by Subject
|
6
|
7
|
|
First Course Treatment
Physician Decision
|
9
|
9
|
|
First Course Treatment
Death
|
3
|
3
|
|
First Course Treatment
Not reported reasons
|
6
|
7
|
|
First Course Treatment
Not treated
|
3
|
3
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Sequence A, Drug: Everolimus First
n=72 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=69 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Total
n=141 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58 years
n=72 Participants
|
58 years
n=69 Participants
|
58 years
n=141 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=72 Participants
|
25 Participants
n=69 Participants
|
56 Participants
n=141 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=72 Participants
|
44 Participants
n=69 Participants
|
85 Participants
n=141 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Eastern cooperative oncology group (ECOG) performance status (PS) at baseline
0
|
50 Participants
n=72 Participants
|
47 Participants
n=69 Participants
|
97 Participants
n=141 Participants
|
|
Eastern cooperative oncology group (ECOG) performance status (PS) at baseline
1
|
20 Participants
n=72 Participants
|
22 Participants
n=69 Participants
|
42 Participants
n=141 Participants
|
|
Eastern cooperative oncology group (ECOG) performance status (PS) at baseline
2
|
2 Participants
n=72 Participants
|
0 Participants
n=69 Participants
|
2 Participants
n=141 Participants
|
|
M-distant metastases at inclusion
Mx
|
1 Participants
n=72 Participants
|
1 Participants
n=69 Participants
|
2 Participants
n=141 Participants
|
|
M-distant metastases at inclusion
M0
|
2 Participants
n=72 Participants
|
6 Participants
n=69 Participants
|
8 Participants
n=141 Participants
|
|
M-distant metastases at inclusion
M1
|
69 Participants
n=72 Participants
|
62 Participants
n=69 Participants
|
131 Participants
n=141 Participants
|
|
Location of metastases at randomization
Bone
|
7 Participants
n=72 Participants
|
10 Participants
n=69 Participants
|
17 Participants
n=141 Participants
|
|
Location of metastases at randomization
Lung
|
2 Participants
n=72 Participants
|
3 Participants
n=69 Participants
|
5 Participants
n=141 Participants
|
|
Location of metastases at randomization
Liver
|
61 Participants
n=72 Participants
|
56 Participants
n=69 Participants
|
117 Participants
n=141 Participants
|
|
Location of metastases at randomization
Lymph nodes
|
4 Participants
n=72 Participants
|
6 Participants
n=69 Participants
|
10 Participants
n=141 Participants
|
|
Ki-67
≤ 2
|
9 Participants
n=72 Participants • patients with analyzable data
|
14 Participants
n=69 Participants • patients with analyzable data
|
23 Participants
n=141 Participants • patients with analyzable data
|
|
Ki-67
3-20
|
62 Participants
n=72 Participants • patients with analyzable data
|
51 Participants
n=69 Participants • patients with analyzable data
|
113 Participants
n=141 Participants • patients with analyzable data
|
|
Ki-67
Unknown
|
1 Participants
n=72 Participants • patients with analyzable data
|
4 Participants
n=69 Participants • patients with analyzable data
|
5 Participants
n=141 Participants • patients with analyzable data
|
|
Tumor Grade
G1
|
9 Participants
n=72 Participants
|
12 Participants
n=69 Participants
|
21 Participants
n=141 Participants
|
|
Tumor Grade
G2
|
63 Participants
n=72 Participants
|
55 Participants
n=69 Participants
|
118 Participants
n=141 Participants
|
|
Tumor Grade
Unknown
|
0 Participants
n=72 Participants
|
2 Participants
n=69 Participants
|
2 Participants
n=141 Participants
|
|
Number of previous systemic treatment lines
0 prior treatment lines
|
36 Participants
n=72 Participants
|
43 Participants
n=69 Participants
|
79 Participants
n=141 Participants
|
|
Number of previous systemic treatment lines
1 prior treatment line
|
32 Participants
n=72 Participants
|
22 Participants
n=69 Participants
|
54 Participants
n=141 Participants
|
|
Number of previous systemic treatment lines
2 prior treatment lines
|
4 Participants
n=72 Participants
|
4 Participants
n=69 Participants
|
8 Participants
n=141 Participants
|
|
Previous treatments
Somatostatic analogs · Yes
|
31 Participants
n=72 Participants
|
24 Participants
n=69 Participants
|
55 Participants
n=141 Participants
|
|
Previous treatments
Somatostatic analogs · No
|
41 Participants
n=72 Participants
|
45 Participants
n=69 Participants
|
86 Participants
n=141 Participants
|
|
Previous treatments
Radiopharmaceuticals · Yes
|
4 Participants
n=72 Participants
|
3 Participants
n=69 Participants
|
7 Participants
n=141 Participants
|
|
Previous treatments
Radiopharmaceuticals · No
|
68 Participants
n=72 Participants
|
66 Participants
n=69 Participants
|
134 Participants
n=141 Participants
|
|
Previous treatments
Others · Yes
|
1 Participants
n=72 Participants
|
1 Participants
n=69 Participants
|
2 Participants
n=141 Participants
|
|
Previous treatments
Others · No
|
71 Participants
n=72 Participants
|
68 Participants
n=69 Participants
|
139 Participants
n=141 Participants
|
PRIMARY outcome
Timeframe: At 12 monthsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs)
Proportion of patients who are alive without progression to Course 1 from the date of randomization in STZ based CT vs Everolimus arms Definitions for PFS rate for course 1 at 12 months: * No: number (proportion) of patients who were not alive and progression free according to the respective definition (main, conservative, and optimistic); * Yes: number (proportion) of patients who were alive and progression free according to the respective definition (main, conservative, and optimistic).
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=72 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=69 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
First Progression Free Survival (PFS1)
|
71.4 percentage of patients alive and PD-free
Interval 59.4 to 81.6
|
61.8 percentage of patients alive and PD-free
Interval 49.2 to 73.3
|
SECONDARY outcome
Timeframe: Until the end of study every 12 weeks, approximately up to 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs)
PFS of Course 1 (PFS1) + interval between treatments + PFS of Course 2 (PFS2), where PFS1 represents progression free survival of Course 1 and PFS2 represents progression free survival of Course 2
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=72 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=69 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Second Progression Free Survival (Second PFS)
|
37.5 months
Interval 27.1 to 53.7
|
32.6 months
Interval 23.7 to 41.1
|
SECONDARY outcome
Timeframe: Throughout the study period every 12 weeks, approximately up to 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs)
Time from the date of randomization to the date of first disease progression.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=72 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=69 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Progression-free Survival (PFS) to First Treatment
|
19.4 months
Interval 16.8 to 27.6
|
22.7 months
Interval 13.3 to 28.6
|
SECONDARY outcome
Timeframe: Throughout the study period in continous monitoring at every visit for approximately up to 5 yearsPopulation: Patients who do not received study treatment were not included in the safety population to analyze safety. The outcome is reported per arm, as the trial was designed to report which sequential strategy is the best in overall. Most patients with panNETs progress and therefore will require to go through both treatments. The main scientific interest is the overall safety/efficacy.
Number of patients expiriencing adverse events, treatment-related AEs and serious adverse events (SAEs)
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=69 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=66 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Adverse Events (AEs) Rate
AEs
|
68 Patients
|
62 Patients
|
|
Adverse Events (AEs) Rate
SAEs
|
28 Patients
|
26 Patients
|
|
Adverse Events (AEs) Rate
Treatment-related AEs
|
66 Patients
|
56 Patients
|
SECONDARY outcome
Timeframe: Throughout the study period, approximately up to 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving study treatment.
Percentage of patients who require a dose reduction or interruption for management of adverse events during the study period
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=68 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=66 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Frequency of Dose Modifications to First Treatment
|
41 Patients
|
9 Patients
|
SECONDARY outcome
Timeframe: Throughout the study period, every 12 weeks up to approximately 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving treatment.
Best response achieved with the first study treatment according to RECIST V1.0
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=69 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=66 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Best Overall Response (BOR) to First Study Treatment
Complete response (CR)
|
3 Participants
|
3 Participants
|
|
Best Overall Response (BOR) to First Study Treatment
Partial response (PR)
|
5 Participants
|
17 Participants
|
|
Best Overall Response (BOR) to First Study Treatment
Stable disease (SD)
|
58 Participants
|
35 Participants
|
|
Best Overall Response (BOR) to First Study Treatment
Progression of the disease (PD)
|
2 Participants
|
9 Participants
|
|
Best Overall Response (BOR) to First Study Treatment
Not evaluable (NE)
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Throughout the study period every 12 weeks, up to approximately 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving study treatment
The ORR is defined as the number of patients having as their BOR to first treatment either Complete response (CR) or Partial Response (PR) measured by RECIST criteria version 1.0.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=69 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=66 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Objective Response Rate (ORR) to First Study Treatment
CR / PR
|
8 Participants
|
20 Participants
|
|
Objective Response Rate (ORR) to First Study Treatment
SD / PD / NE
|
61 Participants
|
46 Participants
|
SECONDARY outcome
Timeframe: Throughout the study period, approximately up to 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving the second-line study treatment.
Percentage of patients who require a dose reduction or interruption for management of adverse events during the study period
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=36 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=33 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Frequency of Dose Modifications to Second Treatment
|
5 Patients
|
18 Patients
|
SECONDARY outcome
Timeframe: Throughout the study period, up to approximately 5 yearsPopulation: Intention to treat population. The outcome is reported per arm rather than intervention, as the trial was designed to demonstrate which sequential strategy is the best in overall. Most patients with panNETs progress and therefore will require to go through both treatments. The main scientific interest is the overall safety/efficacy.
The median OS defined as the time from the date of randomization until death from any cause. This is estimated by kaplan meier method.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=72 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=69 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Overall Survival (OS)
|
61.7 months
Interval 49.1 to
The interval have not reached
|
50.6 months
Interval 40.9 to 64.5
|
SECONDARY outcome
Timeframe: Throughout the study period, every 12 weeks up to approximately 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving the second treatment.
Best response achieved with the second study treatment according to RECIST V1.0
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=36 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=33 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Best Overall Response (BOR) to Second Study Treatment
Complete response (CR)
|
1 Participants
|
0 Participants
|
|
Best Overall Response (BOR) to Second Study Treatment
Partial response (PR)
|
10 Participants
|
3 Participants
|
|
Best Overall Response (BOR) to Second Study Treatment
Stable disease (SD)
|
15 Participants
|
20 Participants
|
|
Best Overall Response (BOR) to Second Study Treatment
Progression of the disease (PD)
|
8 Participants
|
8 Participants
|
|
Best Overall Response (BOR) to Second Study Treatment
Not evaluable (NE)
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Throughout the study period every 12 weeks, up to approximately 5 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs) receiving second study treatment
The ORR is defined as the number of patients having as their BOR to second treatment either Complete response (CR) or Partial Response (PR) measured by RECIST criteria version 1.0.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=36 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=33 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Objective Response Rate (ORR) to Second Study Treatment
CR / PR
|
11 Participants
|
3 Participants
|
|
Objective Response Rate (ORR) to Second Study Treatment
SD / PD / NE
|
25 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: Throughout the study period every 12 weeks, approximately up to 2 yearsPopulation: Patients diagnosed advanced progressive pancreatic neuroendocrine tumours (pNETs)
Time from the date of first dose of second treatment to the date of second disease progression.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=36 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=33 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Progression-free Survival (PFS) to Second Treatment
|
8.8 months
Interval 5.2 to 30.2
|
9.5 months
Interval 6.6 to 19.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Before any dose of study treatment (basal), before the first dose of the second treatment at line 2 cycle 1 (L2C1) and after completion of both treatments (EOT). See outcome measure description for further details.Population: Patients completing the QLQ questionnaires at any timepoint.
Patient self-reported quality of life (QoL) was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire and the specific module for NETs, QLQ-GINET21. These questionnaires have a punctuation that ranges from 100 (best patient performance) to 0 (worse patient performance). Here we report the total QLQ-C30 score. Timepoints: Before any dose of study treatment (basal), before the first dose of the second treatment at line 2 cycle 1 (L2C1) and after completion of both treatments (EOT). Patients changed treatment line and ended both treatments after progression, therefore this outcome is not linked to specific reference timepoints but rather to a relevant disease stage which may happer early or latter in time. All assessments are performed obviously during trial duration, up to approximately 5 years.
Outcome measures
| Measure |
Sequence A, Drug: Everolimus First
n=47 Participants
Everolimus (10mg/daily, oral) followed by STZ-5FU (injection/infusion; Moertel or Uppsala regime).
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
Sequence B, Drug: STZ - 5FU First
n=49 Participants
STZ-5FU (injection/infusion; Moertel or Uppsala regime) followed by Everolimus (10 mg/ daily, oral)
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
Quality of Life Questionnaire (QLQ). The EORTC QLQ-C30 Global Health Status
Basal
|
78.3 Score
Standard Deviation 17.6
|
77.8 Score
Standard Deviation 12.1
|
|
Quality of Life Questionnaire (QLQ). The EORTC QLQ-C30 Global Health Status
L2C1
|
75.1 Score
Standard Deviation 16
|
84.1 Score
Standard Deviation 9.5
|
|
Quality of Life Questionnaire (QLQ). The EORTC QLQ-C30 Global Health Status
EOT
|
68.4 Score
Standard Deviation 15.2
|
75.4 Score
Standard Deviation 17.9
|
Adverse Events
Everolimus
Serious events: 28 serious events
Other events: 68 other events
Deaths: 26 deaths
STZ - 5FU
Serious events: 26 serious events
Other events: 62 other events
Deaths: 35 deaths
Serious adverse events
| Measure |
Everolimus
n=105 participants at risk
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
|
STZ - 5FU
n=104 participants at risk
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
General disorders
Fever
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Sepsis
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.9%
2/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Malaise
|
1.9%
2/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Infection without focus
|
1.9%
2/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Constipation
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Pain
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Nervous system disorders
Dizziness
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Biliary tract infection
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Fatigue
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Nausea
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Urinary tract infection
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Blood and lymphatic system disorders
Anemia
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Weight loss
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Lung infection
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Creatinine increased
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Non-cardiac chest pain
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Gastritis
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Infection
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Localized edema
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Dental caries
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Enterocolitis
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Hepatobiliary disorders
Acute cholangitis
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Appendicitis
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Bacteremia
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Increased urea
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Nervous system disorders
Presyncope
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Renal Calculi
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Vascular disorders
Thromboembolic event
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Stomach pain
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Urotelial carcinoma
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papilloma
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver metastasis
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Cholecystitis
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Vascular disorders
Hypertension
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
Other adverse events
| Measure |
Everolimus
n=105 participants at risk
Drug: Everolimus: 10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
|
STZ - 5FU
n=104 participants at risk
STZ-5FU: 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala).
Number of Cycles: until progression or unacceptable toxicity develops.
|
|---|---|---|
|
General disorders
Fever
|
13.3%
14/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Abdominal pain
|
13.3%
14/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
16.3%
17/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
21.9%
23/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
8.7%
9/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Constipation
|
9.5%
10/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
14.4%
15/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
7.6%
8/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Fatigue
|
37.1%
39/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
35.6%
37/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Nausea
|
20.0%
21/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
25.0%
26/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Urinary tract infection
|
10.5%
11/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
2.9%
3/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Blood and lymphatic system disorders
Anemia
|
9.5%
10/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
2.9%
3/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Weight loss
|
8.6%
9/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Lung infection
|
6.7%
7/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Creatinine increased
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
5.8%
6/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Non-cardiac chest pain
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Mucositis oral
|
32.4%
34/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
15.4%
16/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Diarrhea
|
24.8%
26/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
18.3%
19/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
24.8%
26/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Edema limbs
|
16.2%
17/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Anorexia
|
15.2%
16/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
11.5%
12/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Vomiting
|
11.4%
12/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
12.5%
13/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.4%
12/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
2.9%
3/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
9.5%
10/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
6.7%
7/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Flu like symptoms
|
9.5%
10/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
8.7%
9/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Cholesterol high
|
9.5%
10/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Alanine aminotransferase increased
|
7.6%
8/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Nervous system disorders
Dysgeusia
|
7.6%
8/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.6%
8/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Vascular disorders
Hypertension
|
7.6%
8/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Nervous system disorders
Headache
|
6.7%
7/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
2.9%
3/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Aspartate aminotransferase increased
|
6.7%
7/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
7/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
7.7%
8/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Proteinuria
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
5.8%
6/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Stomach pain
|
5.7%
6/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
2.9%
3/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.8%
5/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
6.7%
7/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
4.8%
5/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Mouth ulcer
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.96%
1/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
1.9%
2/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
GGT increased
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Upper respiratory infection
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Psychiatric disorders
Insomnia
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
7.7%
8/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Skin and subcutaneous tissue disorders
Nail ridging
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Pharyngitis
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Infections and infestations
Skin infection
|
3.8%
4/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
0.00%
0/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
1.9%
2/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
4.8%
5/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Vascular disorders
Thromboembolic event
|
1.9%
2/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
General disorders
Pain in extremity
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
5.8%
6/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Musculoskeletal and connective tissue disorders
Cramps
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Nervous system disorders
Dizziness
|
0.95%
1/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Investigations
Alkaline phosphatase increased
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Dry mouth
|
2.9%
3/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/105 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
3.8%
4/104 • From the time the patient signs IC for the study until 30 days after the intake of the last dose of treatment; up to approximately 5 years
Adverse events and deaths reported "per intervention" (e.g., "Everolimus" and "STZ-5FU") as pre-specified in the protocol.
|
Additional Information
GETNE Secretary
Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE)
Phone: 0034934344412
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place