Trial Outcomes & Findings for Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab (NCT NCT01403610)
NCT ID: NCT01403610
Last Updated: 2019-07-24
Results Overview
Time from initiation study until radiographic progression by RANO criteria
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
28 participants
Primary outcome timeframe
2 years
Results posted on
2019-07-24
Participant Flow
Participant milestones
| Measure |
Cohort 1
Prior to surgery subjects will be assigned to this group in a 2:1 randomization, ie. 2 subjects will be assigned to TH-302 and one to placebo. A single dose of 575 mg/m2 or placebo will be administered pre-operatively with hypoxyprobe-1 at 500 mg/m2 over 20 minutes. Subjects in this group receive TH-302 at a dose of 240mg/m2 post surgery.
|
Cohort 2
Subjects received 340mg/m2 of TH-302 post surgery
|
Cohort 3
Subjects were dosed with 480mg/m2 of TH-302 regardless of whether or not surgery was performed. 3 subjects in this arm had surgery prior to this dose of TH-302.
|
Cohort 4
Subjects in this cohort did not undergo any surgery, a dose of 670mg/m2 was administered to all.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
4
|
13
|
|
Overall Study
COMPLETED
|
3
|
3
|
4
|
13
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1
Prior to surgery subjects will be assigned to this group in a 2:1 randomization, ie. 2 subjects will be assigned to TH-302 and one to placebo. A single dose of 575 mg/m2 or placebo will be administered pre-operatively with hypoxyprobe-1 at 500 mg/m2 over 20 minutes. Subjects in this group receive TH-302 at a dose of 240mg/m2 post surgery.
|
Cohort 2
Subjects received 340mg/m2 of TH-302 post surgery
|
Cohort 3
Subjects were dosed with 480mg/m2 of TH-302 regardless of whether or not surgery was performed. 3 subjects in this arm had surgery prior to this dose of TH-302.
|
Cohort 4
Subjects in this cohort did not undergo any surgery, a dose of 670mg/m2 was administered to all.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
0
|
0
|
|
Overall Study
Didn't recover from surgery sufficiently
|
0
|
3
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Cohort 1
n=3 Participants
Prior to surgery subjects will be assigned to this group in a 2:1 randomization, ie. 2 subjects will be assigned to TH-302 and one to placebo. A single dose of 575 mg/m2 or placebo will be administered pre-operatively with hypoxyprobe-1 at 500 mg/m2 over 20 minutes. Subjects in this group receive TH-302 at a dose of 240mg/m2 post surgery.
|
Cohort 2
n=3 Participants
Subjects received 340mg/m2 of TH-302 post surgery
|
Cohort 3
n=4 Participants
Subjects were dosed with 480mg/m2 of TH-302 regardless of whether or not surgery was performed. 3 subjects in this arm had surgery prior to this dose of TH-302.
|
Cohort 4
n=13 Participants
Subjects in this cohort did not undergo any surgery, a dose of 670mg/m2 was administered to all.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
56 Years
n=3 Participants
|
47 Years
n=3 Participants
|
50 Years
n=4 Participants
|
61 Years
n=13 Participants
|
56 Years
n=23 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=3 Participants
|
2 Participants
n=3 Participants
|
3 Participants
n=4 Participants
|
3 Participants
n=13 Participants
|
9 Participants
n=23 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=3 Participants
|
1 Participants
n=3 Participants
|
1 Participants
n=4 Participants
|
10 Participants
n=13 Participants
|
14 Participants
n=23 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
3 participants
n=3 Participants
|
3 participants
n=3 Participants
|
4 participants
n=4 Participants
|
13 participants
n=13 Participants
|
23 participants
n=23 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: See full published data at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071657/
Time from initiation study until radiographic progression by RANO criteria
Outcome measures
| Measure |
Cohort 1
n=3 Participants
Bevacizumab (Bev) 10mg/kg every 2 weeks plus TH-302 240mg/m2 every 2 weeks (in a 4 week cycle)
|
Cohort 2
n=3 Participants
Bevacizumab (Bev) 10mg/kg every 2 weeks plus TH-302 340mg/m2 every 2 weeks (in a 4 week cycle)
|
Cohort 3
n=4 Participants
Bevacizumab (Bev) 10mg/kg every 2 weeks plus TH-302 480 mg/m2 every 2 weeks (in a 4 week cycle)
|
Cohort 4
n=13 Participants
Bevacizumab (Bev) 10mg/kg every 2 weeks plus TH-302 470 mg/m2 every 2 weeks (in a 4 week cycle)
|
|---|---|---|---|---|
|
Time to Progression
|
11.3 months
Interval 2.7 to 14.0
|
9 months
Interval 7.8 to 14.0
|
15.6 months
Interval 4.5 to 20.0
|
4.5 months
Interval 1.8 to 14.0
|
Adverse Events
Cohort 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 2
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Cohort 3
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Cohort 4
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cohort 1
n=3 participants at risk
240 mg/m2 dosage
|
Cohort 2
n=3 participants at risk
340 mg/m2 dosage
|
Cohort 3
n=4 participants at risk
480 mg/m2 dosage
|
Cohort 4
n=13 participants at risk
670 mg/m2
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
33.3%
1/3 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/13 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
25.0%
1/4 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/13 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
Other adverse events
| Measure |
Cohort 1
n=3 participants at risk
240 mg/m2 dosage
|
Cohort 2
n=3 participants at risk
340 mg/m2 dosage
|
Cohort 3
n=4 participants at risk
480 mg/m2 dosage
|
Cohort 4
n=13 participants at risk
670 mg/m2
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
rash
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
33.3%
1/3 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
23.1%
3/13 • Number of events 3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Gastrointestinal disorders
anal inflammation
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
30.8%
4/13 • Number of events 4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
General disorders
proctitis
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
15.4%
2/13 • Number of events 2 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
15.4%
2/13 • Number of events 2 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Gastrointestinal disorders
stomatitis
|
33.3%
1/3 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
15.4%
2/13 • Number of events 2 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
33.3%
1/3 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
25.0%
1/4 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/13 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Cardiac disorders
Hypertension
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
7.7%
1/13 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/3 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
0.00%
0/4 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
7.7%
1/13 • Number of events 1 • 2 years
Common Terminology Criteria for Adverse Events version 4.0, Grade 3 or higher reported as serious adverse events. Grade 1: Mild; asymptomatic or mild symptoms 2: Moderate; minimal, local or noninvasive intervention indicated 3: Severe or medically significant but not immediately life threatening 4: Life-threatening consequences; urgent intervention indicated. 5: Death
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place