Trial Outcomes & Findings for Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers (NCT NCT01149434)
NCT ID: NCT01149434
Last Updated: 2014-10-06
Results Overview
Determine the mean percent change that JI-101 has on the peak concentration as determined by calculating the AUC (0-inf) of RAD001 in the presence and absence of JI-101
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
19 participants
Primary outcome timeframe
pre-dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing (Cycle 1 Day 1 for RAD001 alone and Cycle 1 Day 8 for RAD001 + JI-101
Results posted on
2014-10-06
Participant Flow
Participant milestones
| Measure |
Pharmacokinetic Arm Phase 1
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
Pharmacodynamic Arm Phase 2
Patients going on the Pharmacodynamic study will receive JI-101 only.
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
15
|
|
Overall Study
COMPLETED
|
4
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers
Baseline characteristics by cohort
| Measure |
Pharmacokinetic Arm - Phase 1
n=4 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus.
|
Pharmacokinetic Arm-Phase II
n=15 Participants
Patients going on the Pharmacodynamic study will receive JI-101 only.
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
72 years
n=5 Participants
|
60 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: pre-dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing (Cycle 1 Day 1 for RAD001 alone and Cycle 1 Day 8 for RAD001 + JI-101Determine the mean percent change that JI-101 has on the peak concentration as determined by calculating the AUC (0-inf) of RAD001 in the presence and absence of JI-101
Outcome measures
| Measure |
Pharmacokinetic Arm
n=4 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Effect of JI 101 on Pharmacokinetics Area Under Curve (AUC) (0-inf) of RAD001
|
165.6 percentage change
Interval 108.6 to 298.0
|
PRIMARY outcome
Timeframe: pre-dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing (Cycle 1 Day 8 for RAD001 + JI101 and Cycle 1 Day 15 for JI-101 aloneDetermine the mean percent change that RAD001 has on the peak concentration as determined by calculating the AUC (0-inf) of JI101 in the presence and absence of RAD001
Outcome measures
| Measure |
Pharmacokinetic Arm
n=4 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Effect of RAD001 on Pharmacokinetics AUC(0-inf) of JI-101
|
95.3 percentage change
Interval 89.5 to 137.5
|
PRIMARY outcome
Timeframe: 2 monthsPopulation: The intent of this trial was to analyze three different cohorts of patients with different diagnosis. This analysis was conducted with 8 of the enrolled patients that had ovarian disease. Patients enrolled on the remaining cohorts were excluded in this analysis. Results were calculated using Kaplan-Meier product limit methods.
progression-free survival at 2 months. We define progression as using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), to detect a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
Pharmacokinetic Arm
n=8 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Progression Free-Survival in the Ovarian Cancer Cohort
|
71.4 percentage of participants
Interval 45.0 to 99.0
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: The intent of this trial was to analyze three different cohorts of patients with different diagnosis. This analysis was conducted with 8 of the enrolled patients that had ovarian disease. The number of patients enrolled on the remaining cohorts were not included in this analysis.
Response Rate determined by the sum of patients achieving complete or partial response to JI-101 as defined by Response Evaluation Criteria in Solid Tumors
Outcome measures
| Measure |
Pharmacokinetic Arm
n=8 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Tumor Response in the Ovarian Cancer Cohort
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 yearsNumber of patients experiencing a grade 2 or higher Adverse Event related to JI101
Outcome measures
| Measure |
Pharmacokinetic Arm
n=4 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Safety and Tolerability of JI-101
|
4 participants
|
SECONDARY outcome
Timeframe: 2 yearsResponse Rate determined by the sum of patients achieving complete or partial response to JI-101 as defined by Response Evaluation Criteria in Solid Tumors. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Outcome measures
| Measure |
Pharmacokinetic Arm
n=4 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Tumor Response
|
0 participants
|
SECONDARY outcome
Timeframe: 2 yearsNumber of patients experiencing a grade 2 or higher Adverse Event related to JI101
Outcome measures
| Measure |
Pharmacokinetic Arm
n=15 Participants
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
|---|---|
|
Safety and Tolerability of JI-101
|
12 Participants
|
Adverse Events
Pharmacokinetic Arm
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Pharmacodynamic Arm
Serious events: 4 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pharmacokinetic Arm
n=4 participants at risk
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
Pharmacodynamic Arm
n=15 participants at risk
Patients going on the Pharmacodynamic study will receive JI-101 only.
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
|
|---|---|---|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Small bowel obstruction
|
0.00%
0/4
|
20.0%
3/15 • Number of events 5
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
Other adverse events
| Measure |
Pharmacokinetic Arm
n=4 participants at risk
Patients going on Pharmacokinetic arm will receive JI-101 \& Everolimus (4 patients only)
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
Everolimus: Everolimus is a signal transduction inhibitor that selectively inhibits mTOR (mammalian target of rapamycin), a key and highly conserved serine-threonine kinase, that is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis, and cell survival. mTOR is the only currently known target of everolimus (1).
|
Pharmacodynamic Arm
n=15 participants at risk
Patients going on the Pharmacodynamic study will receive JI-101 only.
JI-101: JI-101 inhibits angiogenesis, and subsequently tumor growth, by inhibiting three receptor tyrosine kinases: VEGF Receptor Type 2 (VEGFR 2), platelet derived growth factor receptor beta (PDGFR β and Ephrin B4 (EphB4). JI-101 selectively inhibits kinases critical for all three stages of tumor angiogenesis.
|
|---|---|---|
|
Gastrointestinal disorders
abdominal pain
|
25.0%
1/4 • Number of events 1
|
33.3%
5/15 • Number of events 5
|
|
Vascular disorders
anemia
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Anorexia
|
25.0%
1/4 • Number of events 1
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
consitpation
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
dehydration
|
0.00%
0/4
|
6.7%
1/15 • Number of events 2
|
|
Nervous system disorders
depression
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
diarrhea
|
25.0%
1/4 • Number of events 2
|
26.7%
4/15 • Number of events 4
|
|
Blood and lymphatic system disorders
deep vein thrombosis
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Elevated ALT
|
0.00%
0/4
|
13.3%
2/15 • Number of events 4
|
|
Metabolism and nutrition disorders
Elevated AST
|
0.00%
0/4
|
13.3%
2/15 • Number of events 4
|
|
Investigations
fatigue
|
50.0%
2/4 • Number of events 2
|
26.7%
4/15 • Number of events 4
|
|
Nervous system disorders
headache
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Elevated Alk Phos
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Hypertension
|
75.0%
3/4 • Number of events 4
|
66.7%
10/15 • Number of events 12
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
left toe infection
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Blood and lymphatic system disorders
lymphopenia
|
25.0%
1/4 • Number of events 1
|
20.0%
3/15 • Number of events 3
|
|
Investigations
Mouth Soreness
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
nausea
|
25.0%
1/4 • Number of events 1
|
33.3%
5/15 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
right upper quadrant pain
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
small bowel obstruction
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
vomiting
|
25.0%
1/4 • Number of events 1
|
13.3%
2/15 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
|
Investigations
weight loss
|
0.00%
0/4
|
6.7%
1/15 • Number of events 1
|
Additional Information
Sunil Sharma, MD
Huntsman Cancer Institute Unversity of Utah
Phone: 801-585-0255
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place