01.12.2017 | Research article | Ausgabe 1/2017 Open Access

Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods
Study eligibility
Study design and treatment
Efficacy and safety assessments
Results
Patients and study treatment
Characteristics
|
No. of Patients (%)
|
---|---|
Age, years
|
|
Median
|
62
|
Range
|
30–72
|
Sex
|
|
Male
|
4 (17)
|
Female
|
20 (83)
|
Race
|
|
White
|
22 (90)
|
Black
|
0
|
Other
|
2 (10)
|
ECOG performance status
|
|
ECOG 0
|
16 (67)
|
ECOG 1
|
7 (29)
|
ECOG 2
|
1 (4)
|
Tumor type
|
|
Ovarian/fallopian/peritoneal
|
10 (42)
|
Endometrial
|
5 (21)
|
Cervical
|
3 (13)
|
Esophageal
|
2 (8)
|
Urethral
|
1 (4)
|
Vaginal
|
1 (4)
|
Mesothelial
|
1 (4)
|
Salivary
|
1 (4)
|
Prior chemotherapies
a
|
|
0
|
7 (29)
|
1
|
1 (4)
|
2
|
7 (29)
|
3
|
9 (38)
|
Safety
Dose Level
|
Ridaforolimus
mg (days of cycle)
|
Carboplatin (AUC)
|
No. of Patients Enrolled
|
No of Patients evaluable for DLT
a
|
Dose-Limiting Toxicity
|
---|---|---|---|---|---|
1
|
10 (days 1–5, 8–12, 15–19)
|
5
|
4
|
4
|
Two grade 4 neutropenia
|
1A
|
10 (days 1–5, 8–12)
|
5
|
6
|
6
|
Death from sepsis
|
2A
|
20 (days 1–5, 8–12)
|
5
|
4
a
|
3
|
None
|
3A
|
30 (days 1–5, 8–12)
|
5
|
3
|
3
|
None
|
4A
|
30 (days 1–5, 8–12)
|
6
|
7
b
|
6
|
Grade 3 mucositis; grade 4 thrombocytopenia requiring transfusion
|
Grade (number of cycles)
|
Patients
|
|||||
---|---|---|---|---|---|---|
1
|
2
|
3
|
4
|
Number
|
%
|
|
Alkaline phosphatase increased
|
6
|
5
|
21%
|
|||
Dysphagia
|
2
|
2
|
1
|
5
|
21%
|
|
Dyspnea
|
5
|
3
|
2
|
5
|
21%
|
|
Hypoalbuminemia
|
3
|
1
|
1
|
5
|
21%
|
|
Dehydration
|
3
|
5
|
1
|
7
|
29%
|
|
Fever
|
8
|
7
|
29%
|
|||
Hypokalemia
|
11
|
1
|
4
|
2
|
7
|
29%
|
Transaminases increased
|
11
|
7
|
29%
|
|||
Hypertriglyceridemia
|
7
|
1
|
1
|
8
|
33%
|
|
Peripheral sensory neuropathy
|
8
|
3
|
8
|
33%
|
||
Vomiting
|
7
|
1
|
4
|
8
|
33%
|
|
Anorexia
|
7
|
4
|
9
|
38%
|
||
Urinary tract infection
|
1
|
6
|
2
|
9
|
38%
|
|
Diarrhea
|
8
|
6
|
1
|
10
|
42%
|
|
Hyperglycemia
|
18
|
6
|
2
|
10
|
42%
|
|
Hypomagnesemia
|
23
|
6
|
10
|
42%
|
||
Mucositis oral
|
10
|
10
|
2
|
11
|
46%
|
|
White blood cell decreased
|
14
|
14
|
29
|
3
|
12
|
50%
|
Nausea
|
17
|
4
|
3
|
13
|
54%
|
|
Pain
|
7
|
13
|
54%
|
|||
Alopecia
|
8
|
12
|
14
|
58%
|
||
Fatigue
|
14
|
14
|
1
|
15
|
63%
|
|
Anemia
|
21
|
45
|
15
|
20
|
83%
|
|
Platelet count decreased
|
32
|
26
|
14
|
14
|
20
|
83%
|
Neutrophil count decreased
|
8
|
19
|
26
|
20
|
21
|
88%
|
Level 1: RIDA 10 mg; P 175 mg/m2; C 5 (
n = 4)
|
Level 1A: RIDA 10 mg; P 175 mg/m2; C 5 (
n = 6)
|
Level 2A: RIDA 20 mg; P 175 mg/m2; C 5 (
n = 4)
|
Level 3A: RIDA 30 mg; P 175 mg/m2; C 5 (
n = 3)
|
Level 4A: RIDA 30 mg; P 175 mg/m2; C 6 (
n = 7)
|
|||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Grade
|
Total No. of Patients
|
Grade
|
Total No. of Patients
|
Grade
|
Total No. of Patients
|
Grade
|
Total No. of Patients
|
Grade
|
Total No. of Patients
|
||||||||||||||||
1
|
2
|
3
|
4
|
1
|
2
|
3
|
4
|
1
|
2
|
3
|
4
|
1
|
2
|
3
|
4
|
1
|
2
|
3
|
4
|
||||||
Alkaline phosphatase increased
|
2
|
2
|
1
|
1
|
1
|
1
|
1
|
1
|
|||||||||||||||||
Alopecia
|
1
|
1
|
1
|
3
|
4
|
3
|
3
|
2
|
2
|
3
|
2
|
2
|
2
|
||||||||||||
Anemia
|
2
|
2
|
3
|
4
|
3
|
4
|
4
|
3
|
4
|
2
|
4
|
1
|
2
|
2
|
3
|
4
|
5
|
6
|
|||||||
Anorexia
|
1
|
1
|
2
|
1
|
1
|
2
|
2
|
4
|
4
|
||||||||||||||||
Dehydration
|
1
|
1
|
1
|
3
|
3
|
1
|
2
|
1
|
3
|
||||||||||||||||
Diarrhea
|
1
|
1
|
1
|
1
|
2
|
2
|
1
|
3
|
3
|
1
|
1
|
4
|
|||||||||||||
Dysphagia
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
3
|
|||||||||||||||||
Dyspnea
|
1
|
1
|
2
|
2
|
2
|
1
|
2
|
||||||||||||||||||
Fatigue
|
2
|
2
|
2
|
1
|
2
|
3
|
1
|
2
|
2
|
2
|
2
|
3
|
3
|
3
|
1
|
5
|
|||||||||
Fever
|
2
|
2
|
1
|
1
|
1
|
1
|
3
|
3
|
|||||||||||||||||
Hyperglycemia
|
1
|
1
|
1
|
2
|
2
|
2
|
2
|
1
|
2
|
1
|
1
|
2
|
2
|
3
|
|||||||||||
Hypertriglyceridemia
|
1
|
1
|
1
|
2
|
2
|
2
|
2
|
3
|
3
|
||||||||||||||||
Hypoalbuminemia
|
1
|
1
|
2
|
2
|
1
|
3
|
|||||||||||||||||||
Hypokalemia
|
1
|
1
|
2
|
1
|
1
|
1
|
2
|
1
|
1
|
2
|
2
|
3
|
|||||||||||||
Hypomagnesemia
|
1
|
1
|
2
|
2
|
2
|
1
|
2
|
1
|
1
|
4
|
2
|
4
|
|||||||||||||
Mucositis oral
|
1
|
1
|
2
|
2
|
2
|
3
|
2
|
1
|
2
|
3
|
3
|
1
|
4
|
||||||||||||
Nausea
|
1
|
1
|
1
|
1
|
1
|
2
|
1
|
3
|
2
|
2
|
3
|
5
|
1
|
5
|
|||||||||||
Neutrophil count decreased
|
1
|
1
|
2
|
2
|
4
|
4
|
2
|
4
|
5
|
1
|
3
|
1
|
3
|
2
|
1
|
2
|
3
|
2
|
4
|
4
|
3
|
6
|
|||
Pain
|
1
|
1
|
2
|
2
|
3
|
3
|
|||||||||||||||||||
Peripheral sensory neuropathy
|
1
|
1
|
1
|
3
|
1
|
3
|
1
|
1
|
1
|
1
|
2
|
2
|
|||||||||||||
Platelet count decreased
|
1
|
4
|
4
|
3
|
1
|
1
|
3
|
4
|
3
|
2
|
1
|
4
|
1
|
1
|
1
|
2
|
3
|
3
|
4
|
4
|
4
|
6
|
|||
Transaminases increased
|
1
|
1
|
3
|
3
|
1
|
1
|
|||||||||||||||||||
Urinary tract infection
|
1
|
1
|
2
|
1
|
1
|
1
|
3
|
1
|
4
|
||||||||||||||||
Vomiting
|
1
|
1
|
2
|
2
|
1
|
1
|
1
|
1
|
1
|
1
|
1
|
3
|
|||||||||||||
White blood cell decreased
|
4
|
2
|
4
|
5
|
1
|
2
|
2
|
1
|
3
|
1
|
1
|
1
|
2
|
2
|
3
|