Trial Outcomes & Findings for FR901228 in Treating Patients With Recurrent High-Grade Gliomas (NCT NCT00085540)
NCT ID: NCT00085540
Last Updated: 2017-01-02
Results Overview
dose limiting toxicity defined as: ANC \</=1000 or Platelets \<100K; SGOT \>/= 3X ULN and T. Bili \>/= 1.5 ULN grade 3 Nausea, vomiting, fatigue and asymptomatic hypocalcemia (treatment may continue after discuss with PI)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
50 participants
Primary outcome timeframe
First 4 weeks of treatment
Results posted on
2017-01-02
Participant Flow
Participant milestones
| Measure |
Phase 1 Dose Escalation - Romidepsin
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
Phase 2 Dose From Phase 1 - Romidepsin
Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Romidepsin (depsipeptide): 13.3mg/m2
depsipeptide: Given IV
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
42
|
|
Overall Study
COMPLETED
|
8
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Phase 1 Dose Escalation - Romidepsin
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
Phase 2 Dose From Phase 1 - Romidepsin
Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Romidepsin (depsipeptide): 13.3mg/m2
depsipeptide: Given IV
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
FR901228 in Treating Patients With Recurrent High-Grade Gliomas
Baseline characteristics by cohort
| Measure |
Phase 1 Dose Escalation - Romidepsin
n=8 Participants
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
Phase 2 Dose From Phase 1 - Romidepsin
n=40 Participants
Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Romidepsin (depsipeptide): 13.3mg/m2
depsipeptide: Given IV
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
55 years
n=7 Participants
|
54 years
n=5 Participants
|
|
Gender
Female
|
3 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Gender
Male
|
5 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Karnofsky Performance Status Scale (KPS)
90-100
|
4 units on a scale
n=5 Participants
|
19 units on a scale
n=7 Participants
|
23 units on a scale
n=5 Participants
|
|
Karnofsky Performance Status Scale (KPS)
60-80
|
4 units on a scale
n=5 Participants
|
21 units on a scale
n=7 Participants
|
25 units on a scale
n=5 Participants
|
|
Histology
Anaplastic glioma
|
2 participants
n=5 Participants
|
5 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Histology
Gliobastoma
|
6 participants
n=5 Participants
|
35 participants
n=7 Participants
|
41 participants
n=5 Participants
|
|
Prior Radiotherapy
|
8 participants
n=5 Participants
|
40 participants
n=7 Participants
|
48 participants
n=5 Participants
|
|
Prior chemotherapy regimens
|
1 number of chemotherapy regimens
n=5 Participants
|
1 number of chemotherapy regimens
n=7 Participants
|
1 number of chemotherapy regimens
n=5 Participants
|
PRIMARY outcome
Timeframe: First 4 weeks of treatmentdose limiting toxicity defined as: ANC \</=1000 or Platelets \<100K; SGOT \>/= 3X ULN and T. Bili \>/= 1.5 ULN grade 3 Nausea, vomiting, fatigue and asymptomatic hypocalcemia (treatment may continue after discuss with PI)
Outcome measures
| Measure |
Phase 1 Dose Escalation - Romidepsin
n=8 Participants
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
|---|---|
|
Number of Participants With Dose-limiting Toxicities Due to Romidepsin Graded According to the NCI Common Toxicity Criteria (CTCAE Version 3.0) (Phase I)
|
0 participants
|
PRIMARY outcome
Timeframe: At 6 monthsPopulation: evaluation of patients with GBM histology
evaluated patients with glioblastoma (GBM (35 patients)
Outcome measures
| Measure |
Phase 1 Dose Escalation - Romidepsin
n=35 Participants
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
|---|---|
|
6 Months Progression-free Survival (Phase II)
|
3 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: GBM patients - no responses
RECIST Complete Response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients must be on no steroids. Partial Response (PR): Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/No Response: Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening or failure to return for evaluation due to death or deteriorating condition
Outcome measures
| Measure |
Phase 1 Dose Escalation - Romidepsin
n=35 Participants
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
|---|---|
|
Response Rate Associated With Depsipeptide Therapy (Phase II)
|
0 participants
|
Adverse Events
Phase 1 Dose Escalation - Romidepsin
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Phase 2 Dose From Phase 1 - Romidepsin
Serious events: 0 serious events
Other events: 40 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Phase 1 Dose Escalation - Romidepsin
n=8 participants at risk
Patients receive FR901228 (romidepsin) IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dose escalation two dose levels:
Romidepsin (depsipeptide): 13.3mg/m2 and 17.7mg/m2
Pharmacokinetics
depsipeptide: Given IV
|
Phase 2 Dose From Phase 1 - Romidepsin
n=40 participants at risk
Patients receive FR901228 (romidepsin) as in phase I at dose level 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
Romidepsin (depsipeptide): 13.3mg/m2
depsipeptide: Given IV
|
|---|---|---|
|
Blood and lymphatic system disorders
anemia
|
37.5%
3/8 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
20.0%
8/40 • Number of events 8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Blood and lymphatic system disorders
Leucopenia
|
37.5%
3/8 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
20.0%
8/40 • Number of events 8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Blood and lymphatic system disorders
neutropenia
|
37.5%
3/8 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
17.5%
7/40 • Number of events 7 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Investigations
lymphopenia
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
22.5%
9/40 • Number of events 9 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
75.0%
6/8 • Number of events 6 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
37.5%
15/40 • Number of events 15 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Investigations
Alkaline phosphatase elevation
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
2.5%
1/40 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Investigations
elevated ALT and/or AST
|
25.0%
2/8 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
22.5%
9/40 • Number of events 9 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
anorexia
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
10.0%
4/40 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
hyperglycemia
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
10.0%
4/40 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
hypocalcemia
|
25.0%
2/8 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
5.0%
2/40 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
hypogycemia
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
0.00%
0/40 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
hyponatremia
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
2.5%
1/40 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
hypophosphatemia
|
37.5%
3/8 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
12.5%
5/40 • Number of events 5 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
General disorders
fatigue
|
50.0%
4/8 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
42.5%
17/40 • Number of events 17 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Musculoskeletal and connective tissue disorders
muscle weakness (lower extremity)
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
5.0%
2/40 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Nervous system disorders
headache
|
50.0%
4/8 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
2.5%
1/40 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Vascular disorders
hot flashes
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
0.00%
0/40 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
General disorders
gait disturbance
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
0.00%
0/40 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
nausea
|
62.5%
5/8 • Number of events 5 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
32.5%
13/40 • Number of events 13 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
General disorders
rigors or chills
|
12.5%
1/8 • Number of events 1 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
0.00%
0/40 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
vomiting
|
50.0%
4/8 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
7.5%
3/40 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
constipation
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
17.5%
7/40 • Number of events 7 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
10.0%
4/40 • Number of events 4 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
heartburn
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
5.0%
2/40 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
General disorders
edema-limb
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
5.0%
2/40 • Number of events 2 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
7.5%
3/40 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Nervous system disorders
Dizziness
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
7.5%
3/40 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
7.5%
3/40 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.00%
0/8 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
7.5%
3/40 • Number of events 3 • 2 years
in the phase 1 portion of the study the DLT were reviewed in the first 4 weeks only
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60