Trial Outcomes & Findings for RAD001, FOLFOX and Bevacizumab in Treatment of Colorectal Carcinoma (NCT NCT01047293)
NCT ID: NCT01047293
Last Updated: 2017-04-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
47 participants
Primary outcome timeframe
6 months
Results posted on
2017-04-04
Participant Flow
Participant milestones
| Measure |
ARM 1 RAD001 5 mg QOD
Patients received 5mg RAD001 with FOLFOX and bevacizumab.
|
ARM 2 5mg RAD001 QD
Patients received 5mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 3 10mg RAD001 QD
Patients received 10mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 4 10mg RAD001 QD - Phase II
Patients received 10 mg RAD001 with FOLFOX and bevacizumab. - Patient in the Dose Expansion Cohort not Dose Escalation
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
8
|
9
|
26
|
|
Overall Study
COMPLETED
|
3
|
7
|
9
|
26
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
ARM 1 RAD001 5 mg QOD
Patients received 5mg RAD001 with FOLFOX and bevacizumab.
|
ARM 2 5mg RAD001 QD
Patients received 5mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 3 10mg RAD001 QD
Patients received 10mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 4 10mg RAD001 QD - Phase II
Patients received 10 mg RAD001 with FOLFOX and bevacizumab. - Patient in the Dose Expansion Cohort not Dose Escalation
|
|---|---|---|---|---|
|
Overall Study
DLT criteria not fulfilled
|
1
|
1
|
0
|
0
|
Baseline Characteristics
RAD001, FOLFOX and Bevacizumab in Treatment of Colorectal Carcinoma
Baseline characteristics by cohort
| Measure |
All Patients
n=47 Participants
|
|---|---|
|
Age, Continuous
|
51 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Progression free survival at six month was calculated using all patients receiving one dose of drug therapy at all of the different dosing levels. The six month progression free survival was determined using Kaplan Meier methods
Outcome measures
| Measure |
All Patients
n=47 Participants
|
ARM 2 5mg RAD001 QD
Patients received 5mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 3 10mg RAD001 QD
Patients received 10mg RAD001 QD with FOLFOX and bevacizumab.
|
|---|---|---|---|
|
Progression Free Survival at Six Months
|
87 percentage of participants
Interval 76.0 to 99.9
|
—
|
—
|
PRIMARY outcome
Timeframe: December 2011Number of patients who experienced a Dose Limiting Toxicity (DLT). DLT will be assessed in the first 28 days of dosing. Patients need to get dosed with 2 rounds/sessions of all chemotherapy agents in the first 28 days in order to be evaluable for DLT assessment. The primary endpoint is safety as summarized by dose limiting toxicity (DLT).
Outcome measures
| Measure |
All Patients
n=3 Participants
|
ARM 2 5mg RAD001 QD
n=7 Participants
Patients received 5mg RAD001 QD with FOLFOX and bevacizumab.
|
ARM 3 10mg RAD001 QD
n=9 Participants
Patients received 10mg RAD001 QD with FOLFOX and bevacizumab.
|
|---|---|---|---|
|
Evaluate Safety of the Combination at a Daily Dosing of 2.5mg RAD001, 5 mg RAD001 or 10 mg RAD001 (Phase 1 Part)
|
0 participants
|
1 participants
|
1 participants
|
Adverse Events
All Patients
Serious events: 18 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Patients
n=47 participants at risk
All participants enrolled.
|
|---|---|
|
Blood and lymphatic system disorders
anemia
|
6.4%
3/47 • Number of events 4
|
|
Gastrointestinal disorders
bowel perforation
|
8.5%
4/47 • Number of events 5
|
|
Infections and infestations
c-diff infection
|
4.3%
2/47 • Number of events 3
|
|
Gastrointestinal disorders
cholecystitis
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
confusion
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
dehydration
|
6.4%
3/47 • Number of events 3
|
|
Gastrointestinal disorders
diarrhea
|
4.3%
2/47 • Number of events 2
|
|
Blood and lymphatic system disorders
Deep Vein Thrombosis
|
4.3%
2/47 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
2.1%
1/47 • Number of events 1
|
|
Investigations
failure to thrive
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
febrile neutropenia
|
6.4%
3/47 • Number of events 3
|
|
General disorders
fever
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
fistula - small bowel
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Infection - hepatic
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Infection - pseudomonas
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
infection - urinary tract
|
4.3%
2/47 • Number of events 2
|
|
Infections and infestations
Infections and other systemic inflammatory syndrome
|
2.1%
1/47 • Number of events 1
|
|
Cardiac disorders
left ventricular systolic dysfunction
|
2.1%
1/47 • Number of events 1
|
|
Metabolism and nutrition disorders
lipase increased
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
mucositis
|
8.5%
4/47 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
muscle weakness
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
neutropenia
|
4.3%
2/47 • Number of events 3
|
|
Gastrointestinal disorders
pain - abdominal
|
6.4%
3/47 • Number of events 3
|
|
General disorders
pain - chest
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
pain - rectal/anal
|
2.1%
1/47 • Number of events 1
|
|
Gastrointestinal disorders
pancreatitis
|
4.3%
2/47 • Number of events 2
|
|
Cardiac disorders
pericarditis
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia - aspiration
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
pulmonary emboli
|
6.4%
3/47 • Number of events 3
|
|
Renal and urinary disorders
Renal calculi
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
thrush
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
vasospasms
|
4.3%
2/47 • Number of events 2
|
|
Gastrointestinal disorders
vomiting
|
2.1%
1/47 • Number of events 1
|
|
Investigations
weight loss
|
2.1%
1/47 • Number of events 1
|
Other adverse events
| Measure |
All Patients
n=47 participants at risk
All participants enrolled.
|
|---|---|
|
General disorders
body aches
|
6.4%
3/47 • Number of events 4
|
|
Metabolism and nutrition disorders
alkaline phosphatase increased
|
12.8%
6/47 • Number of events 7
|
|
Immune system disorders
allergic reaction - anaphylactic
|
8.5%
4/47 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
alopecia
|
23.4%
11/47 • Number of events 12
|
|
Investigations
Alanine aminotransferase increased
|
12.8%
6/47 • Number of events 8
|
|
Blood and lymphatic system disorders
anemia
|
25.5%
12/47 • Number of events 22
|
|
Gastrointestinal disorders
anorexia
|
53.2%
25/47 • Number of events 52
|
|
Psychiatric disorders
anxiety
|
6.4%
3/47 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
8.5%
4/47 • Number of events 4
|
|
Investigations
Aspartate aminotransferase increased
|
10.6%
5/47 • Number of events 6
|
|
Nervous system disorders
ataxia
|
6.4%
3/47 • Number of events 6
|
|
Injury, poisoning and procedural complications
bruising
|
8.5%
4/47 • Number of events 4
|
|
Infections and infestations
c-diff infection
|
6.4%
3/47 • Number of events 6
|
|
Psychiatric disorders
confusion
|
6.4%
3/47 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
congestion - sinus
|
27.7%
13/47 • Number of events 14
|
|
Gastrointestinal disorders
constipation
|
25.5%
12/47 • Number of events 31
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
34.0%
16/47 • Number of events 28
|
|
Investigations
creatinine increased
|
8.5%
4/47 • Number of events 6
|
|
Metabolism and nutrition disorders
dehydration
|
42.6%
20/47 • Number of events 29
|
|
Psychiatric disorders
depression
|
17.0%
8/47 • Number of events 10
|
|
Gastrointestinal disorders
diarrhea
|
78.7%
37/47 • Number of events 86
|
|
Nervous system disorders
dizziness
|
14.9%
7/47 • Number of events 7
|
|
Gastrointestinal disorders
dry mouth
|
6.4%
3/47 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
dry skin
|
21.3%
10/47 • Number of events 12
|
|
Vascular disorders
deep vein thrombosis
|
12.8%
6/47 • Number of events 6
|
|
Gastrointestinal disorders
dysgeusia
|
38.3%
18/47 • Number of events 22
|
|
Gastrointestinal disorders
dysphagia
|
17.0%
8/47 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
23.4%
11/47 • Number of events 20
|
|
Renal and urinary disorders
dysuria
|
6.4%
3/47 • Number of events 4
|
|
General disorders
edemia - penile/groin
|
36.2%
17/47 • Number of events 25
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
61.7%
29/47 • Number of events 39
|
|
General disorders
fatigue
|
91.5%
43/47 • Number of events 88
|
|
General disorders
fever
|
25.5%
12/47 • Number of events 15
|
|
Gastrointestinal disorders
flatulence
|
17.0%
8/47 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Erythroderma
|
27.7%
13/47 • Number of events 23
|
|
Nervous system disorders
headache
|
46.8%
22/47 • Number of events 27
|
|
Renal and urinary disorders
hematuria
|
8.5%
4/47 • Number of events 5
|
|
Vascular disorders
hemorrhage - rectal
|
6.4%
3/47 • Number of events 3
|
|
Gastrointestinal disorders
hemorrhoids
|
10.6%
5/47 • Number of events 7
|
|
Investigations
hypercholesterolemia
|
8.5%
4/47 • Number of events 5
|
|
Metabolism and nutrition disorders
hyperglycemia
|
17.0%
8/47 • Number of events 13
|
|
Vascular disorders
hypertension
|
25.5%
12/47 • Number of events 23
|
|
Metabolism and nutrition disorders
hypertriglyceridemia
|
19.1%
9/47 • Number of events 15
|
|
Metabolism and nutrition disorders
hypocalcemia
|
12.8%
6/47 • Number of events 7
|
|
Metabolism and nutrition disorders
hypokalemia
|
36.2%
17/47 • Number of events 36
|
|
Metabolism and nutrition disorders
hyponatremia
|
6.4%
3/47 • Number of events 4
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
25.5%
12/47 • Number of events 29
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
10.6%
5/47 • Number of events 6
|
|
Infections and infestations
infection - gums
|
6.4%
3/47 • Number of events 4
|
|
Infections and infestations
infection - tooth
|
6.4%
3/47 • Number of events 3
|
|
Infections and infestations
infection - urine/yeast
|
27.7%
13/47 • Number of events 29
|
|
Infections and infestations
infection - vaginial
|
8.5%
4/47 • Number of events 8
|
|
Psychiatric disorders
insomnia
|
21.3%
10/47 • Number of events 11
|
|
Blood and lymphatic system disorders
leukopenia
|
34.0%
16/47 • Number of events 37
|
|
Blood and lymphatic system disorders
lymphopenia
|
10.6%
5/47 • Number of events 7
|
|
General disorders
malaise
|
6.4%
3/47 • Number of events 3
|
|
Gastrointestinal disorders
mucositis
|
85.1%
40/47 • Number of events 146
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
14.9%
7/47 • Number of events 7
|
|
General disorders
nail changes
|
14.9%
7/47 • Number of events 7
|
|
Gastrointestinal disorders
nausea
|
78.7%
37/47 • Number of events 83
|
|
Nervous system disorders
neuropathy
|
87.2%
41/47 • Number of events 95
|
|
Blood and lymphatic system disorders
neutropenia
|
72.3%
34/47 • Number of events 102
|
|
General disorders
night sweats
|
10.6%
5/47 • Number of events 5
|
|
Gastrointestinal disorders
pain - unspecified
|
6.4%
3/47 • Number of events 3
|
|
General disorders
pain - abdominal
|
44.7%
21/47 • Number of events 36
|
|
General disorders
pain - back
|
29.8%
14/47 • Number of events 22
|
|
General disorders
pain - chest
|
27.7%
13/47 • Number of events 17
|
|
General disorders
pain - extremity
|
14.9%
7/47 • Number of events 11
|
|
Gastrointestinal disorders
pain - rectal/anal
|
19.1%
9/47 • Number of events 16
|
|
General disorders
pain - shoulders
|
6.4%
3/47 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
pleural effusion
|
8.5%
4/47 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
pneumonitis
|
6.4%
3/47 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
post nasal drip
|
17.0%
8/47 • Number of events 8
|
|
Renal and urinary disorders
proteinuria
|
17.0%
8/47 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary emboli
|
10.6%
5/47 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
rash
|
36.2%
17/47 • Number of events 25
|
|
Skin and subcutaneous tissue disorders
rash - acneiform
|
6.4%
3/47 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
rash - pruritic
|
14.9%
7/47 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
sore throat
|
29.8%
14/47 • Number of events 18
|
|
Cardiac disorders
tachycardia - sinus
|
12.8%
6/47 • Number of events 8
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
34.0%
16/47 • Number of events 50
|
|
Infections and infestations
thrush
|
19.1%
9/47 • Number of events 10
|
|
General disorders
toothache
|
6.4%
3/47 • Number of events 3
|
|
General disorders
voice changes
|
12.8%
6/47 • Number of events 7
|
|
Gastrointestinal disorders
vomiting
|
53.2%
25/47 • Number of events 39
|
|
Investigations
weight loss
|
59.6%
28/47 • Number of events 59
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place