Trial Outcomes & Findings for Vorinostat, Paclitaxel, and Radiation Therapy in Treating Patients Unable to Tolerate Cisplatin With Stage III Non-Small Lung Cancer That Cannot Be Removed By Surgery (NCT NCT00662311)
NCT ID: NCT00662311
Last Updated: 2017-06-14
Results Overview
Defined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted \> 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade \> 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
5 participants
Primary outcome timeframe
8 weeks
Results posted on
2017-06-14
Participant Flow
Participant milestones
| Measure |
Vorinostat 200 mg
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
0
|
0
|
|
Overall Study
COMPLETED
|
4
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Vorinostat 200 mg
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Overall Study
Respiratory Infection
|
1
|
0
|
0
|
Baseline Characteristics
Vorinostat, Paclitaxel, and Radiation Therapy in Treating Patients Unable to Tolerate Cisplatin With Stage III Non-Small Lung Cancer That Cannot Be Removed By Surgery
Baseline characteristics by cohort
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Total
n=5 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
77 years
n=5 Participants
|
—
|
—
|
77 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
—
|
—
|
3 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
—
|
—
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
—
|
—
|
5 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 8 weeksDefined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted \> 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade \> 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.
Outcome measures
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
MTD of Vorinostat When Administered in Combination With Paclitaxel and Radiotherapy Therapy as Assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)
|
NA mg
Due to adverse events we were unable to increase the vorinostat dosing beyond the first cohort of 200mg. The study was terminated prior to identifying the MTD.
|
—
|
—
|
SECONDARY outcome
Timeframe: 12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafterCount of participants with stable disease or partial response. Patients were evaluated for treatment response per RECIST criteria (version 1.0).
Outcome measures
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Radiological Response Rate as Assessed by CT
12 Weeks
|
4 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
6 Months
|
3 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
9 Months
|
3 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
12 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
15 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
18 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
21 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
24 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
27 Months
|
1 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
33 Months
|
0 Participants
|
—
|
—
|
|
Radiological Response Rate as Assessed by CT
39 Months
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 3 yearsOutcome measures
| Measure |
Vorinostat 200 mg
n=4 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Duration of Response
|
10 months
Interval 6.0 to 28.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 yearKaplan-Meier estimate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
Outcome measures
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Progression-free Survival
|
0.20 progression free survival probability
Interval 0.035 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 yearKaplan-Meier estimate
Outcome measures
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Overall Survival
|
0.60 survival probability
Interval 0.29 to 1.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatmentCount of participants with a grade 3 or higher toxicity. Toxicities were assessed using the NCI CTCAE (v3.0). Grade 3 or higher toxicities were considered worse.
Outcome measures
| Measure |
Vorinostat 200 mg
n=5 Participants
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0
|
4 Participants
|
—
|
—
|
Adverse Events
Vorinostat 200 mg
Serious events: 4 serious events
Other events: 0 other events
Deaths: 0 deaths
Vorinostat 300 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Vorinostat 400 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat 200 mg
n=5 participants at risk
Cohort 1: Patients receive 200 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 300 mg
Cohort 2: Patients receive 300 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
Vorinostat 400 mg
Cohort 3: Patients receive 400 mg vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
paclitaxel: Given IV
radiation therapy: Undergo radiation therapy
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Hyponatremia
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Community Contacted Pneumonia
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration Pneumonia
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Radiation Pneumonitis
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
General disorders
Fatigue
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
|
Gastrointestinal disorders
Esophagitis
|
20.0%
1/5
|
—
0/0
|
—
0/0
|
Other adverse events
Adverse event data not reported
Additional Information
Shilpen Patel
Departments of Radiation Oncology and Global Health University of Washington Medical Center
Phone: 206-598-4100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place