Trial Outcomes & Findings for Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases (NCT NCT00838929)
NCT ID: NCT00838929
Last Updated: 2025-05-04
Results Overview
To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Vorinostat and radiotherapy in patients with brain metastases. The maximum tolerated dose (MTD) will be one dose below the DLT occurring in at least 1 out of 3 subjects. Dose level -2: 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1: 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I: 200 mg PO qd (initial starting dose) Dose level II: 300 mg PO qd Dose level III: 400 mg PO qd
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
17 participants
Primary outcome timeframe
Weekly during treatment On Last day of treatment (30 days after last drug dose) Follow-up (every 3 months)
Results posted on
2025-05-04
Participant Flow
Participant milestones
| Measure |
Vorinostat (200 mg) and Radiation
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level -2 - 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1 - 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I - 200 mg PO qd (initial starting dose) Dose level II - 300 mg PO qd Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (300 mg) and Radiation
|
Vorinostat (400 mg) and Radiation
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
8
|
6
|
|
Overall Study
COMPLETED
|
3
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
1
|
Reasons for withdrawal
| Measure |
Vorinostat (200 mg) and Radiation
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level -2 - 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1 - 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I - 200 mg PO qd (initial starting dose) Dose level II - 300 mg PO qd Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (300 mg) and Radiation
|
Vorinostat (400 mg) and Radiation
|
|---|---|---|---|
|
Overall Study
Protocol Violation
|
0
|
1
|
0
|
|
Overall Study
Disease progression
|
0
|
2
|
1
|
Baseline Characteristics
Study of the Combination of Vorinostat and Radiation Therapy for the Treatment of Patients With Brain Metastases
Baseline characteristics by cohort
| Measure |
Vorinostat (200 mg) and Radiation
n=3 Participants
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level I - 200 mg PO qd (initial starting dose)
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (300 mg) and Radiation
n=8 Participants
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level II - 300 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (400 mg) and Radiation
n=6 Participants
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Total
n=17 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
8 participants
n=7 Participants
|
6 participants
n=5 Participants
|
17 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Weekly during treatment On Last day of treatment (30 days after last drug dose) Follow-up (every 3 months)To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Vorinostat and radiotherapy in patients with brain metastases. The maximum tolerated dose (MTD) will be one dose below the DLT occurring in at least 1 out of 3 subjects. Dose level -2: 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1: 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I: 200 mg PO qd (initial starting dose) Dose level II: 300 mg PO qd Dose level III: 400 mg PO qd
Outcome measures
| Measure |
Vorinostat and Radiation - All Participants
n=13 Participants
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level -2 - 50 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level -1 - 100 mg PO qd (to be used in de-escalation if toxicity occurs) Dose level I - 200 mg PO qd (initial starting dose) Dose level II - 300 mg PO qd Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
|---|---|
|
Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of Vorinostat and Radiotherapy in Patients With Brain Metastases.
|
300 mg
|
Adverse Events
Vorinostat (200 mg) and Radiation
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Vorinostat (300 mg) and Radiation
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Vorinostat (400 mg) and Radiation
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat (200 mg) and Radiation
n=3 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level I - 200 mg PO qd (initial starting dose)
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (300 mg) and Radiation
n=7 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level II - 300 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (400 mg) and Radiation
n=6 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
|---|---|---|---|
|
Gastrointestinal disorders
Increase in amylase
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
0.00%
0/6
|
|
Nervous system disorders
Death
|
0.00%
0/3
|
0.00%
0/7
|
33.3%
2/6 • Number of events 2
|
|
Vascular disorders
Pulmonary embolism
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Ulceration - Grade 3
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
Other adverse events
| Measure |
Vorinostat (200 mg) and Radiation
n=3 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level I - 200 mg PO qd (initial starting dose)
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (300 mg) and Radiation
n=7 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level II - 300 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
Vorinostat (400 mg) and Radiation
n=6 participants at risk
Patients will be treated on a dose escalation model for vorinostat and concurrently receive radiation therapy.
Vorinostat : All doses given for 3 weeks
Dose level III - 400 mg PO qd
Radiation Therapy : Patients will take Vorinostat daily during radiation therapy, they will be recommended to swallow the capsule 60-90 minutes prior to estimate time of radiation.
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Oral pain
|
33.3%
1/3 • Number of events 1
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Ulceration - Grade 2
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
0.00%
0/6
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Vomiting
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Ataxia
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Nausea
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Investigations
Partial thromboplastin time prolonged
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Increased blood alkaline phosphatase
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Low hemoglobin
|
0.00%
0/3
|
28.6%
2/7 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
|
Investigations
Prothrombin time prolonged
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Hyperglycemia
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Cystitis
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
33.3%
1/3 • Number of events 1
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Headache
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Increased alanine aminotransferase
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 2
|
|
General disorders
Constipation
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
Blood and lymphatic system disorders
Low platelets
|
0.00%
0/3
|
0.00%
0/7
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Alopecia
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Low sodium
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Hypermagnesemia
|
0.00%
0/3
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Anorexia
|
0.00%
0/3
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place