Trial Outcomes & Findings for Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT01413750)

Last Updated: 2024-11-12

Results Overview

Estimated using the product-limit method of Kaplan and Meier. PFS defined as time from randomization to progression or death due to any cause. Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as 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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year

Results posted on

2024-11-12

Participant Flow

Participant milestones

Participant milestones
Measure	Phase I: Dose Level 1 Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 600 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase I: Dose Level 2 Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Vorinostat Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Study STARTED	6	6	4	7
Overall Study COMPLETED	6	6	4	7
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Carboplatin and Paclitaxel With or Without Vorinostat in Treating Patients With Advanced Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Dose Level 1 n=6 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 600 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase I: Dose Level 2 n=6 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II (Vorinostat) n=4 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II (Placebo) n=7 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies	Total n=23 Participants Total of all reporting groups
Age, Continuous	61 years n=5 Participants	59 years n=7 Participants	72 years n=5 Participants	65 years n=4 Participants	63 years n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	7 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	16 Participants n=21 Participants
Region of Enrollment United States	6 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	7 participants n=4 Participants	23 participants n=21 Participants

PRIMARY outcome

Timeframe: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year

Population: Due to early termination phase II portion of the study did not reach planned accrual.

Outcome measures

Outcome measures
Measure	Phase II: Vorinostat n=4 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo n=7 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Progression-free Survival (PFS)	4.1 months Interval 0.5 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	7.3 months Interval 0.4 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: 4 weeks from start of treatment, up to 1 year

DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (\> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count \< 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet \< 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever \> 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD.

Outcome measures

Outcome measures
Measure	Phase II: Vorinostat n=6 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo n=6 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Dose Limiting Toxicity (DLT) (Phase I)	1 participants with DLTs	0 participants with DLTs

SECONDARY outcome

Timeframe: 4 weeks from start of treatment, up to 1 year

The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD.

Outcome measures

Outcome measures
Measure	Phase II: Vorinostat n=12 Participants Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Maximum Tolerated Dose (MTD) (Phase I)	800 mg	—

Adverse Events

Phase I: Dose Level 1

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase I: Dose Level 2

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II: Vorinostat

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase II: Placebo

Serious events: 5 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

DCC Project Administrator

California Cancer Consortium

Phone: 626-256-4673

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Phase I: Dose Level 1 n=6 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 600 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase I: Dose Level 2 n=6 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Vorinostat n=4 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Voninostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo n=7 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Blood and lymphatic system disorders Anemia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Esophageal fistula	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Sudden death NOS	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Sepsis	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	28.6% 2/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	50.0% 3/6 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 2/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	57.1% 4/7 • Number of events 7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations White blood cell decreased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	28.6% 2/7 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	28.6% 2/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Stroke	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Renal and urinary disorders Urinary retention	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Hypotension	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thromboembolic event	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events
Measure	Phase I: Dose Level 1 n=6 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 600 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase I: Dose Level 2 n=6 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients also receive 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Vorinostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Vorinostat n=4 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to 800 mg QD of Vorinostat on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Voninostat: Given PO Laboratory Biomarker Analysis: Correlative studies	Phase II: Placebo n=7 participants at risk Patients receive A fixed dose of Carboplatin at AUC 6 mg/ml.min iv on day 0 of each cycle and Paclitaxel 200 mg/m2, iv on day 0 of each cycle. Patients randomized to placebo on days -2 to 2. Each cycle is 21 days. Paclitaxel: Given IV Carboplatin: Given IV Placebo: Given PO Laboratory Biomarker Analysis: Correlative studies
Gastrointestinal disorders Bloating	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	33.3% 2/6 • Number of events 8 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	28.6% 2/7 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	50.0% 3/6 • Number of events 6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 2/6 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Flatulence	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 3/6 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	42.9% 3/7 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Stomach pain	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	66.7% 4/6 • Number of events 12 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	83.3% 5/6 • Number of events 8 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	85.7% 6/7 • Number of events 22 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Injection site reaction	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Non-cardiac chest pain	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Blood and lymphatic system disorders Anemia	83.3% 5/6 • Number of events 20 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	83.3% 5/6 • Number of events 11 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 14 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	85.7% 6/7 • Number of events 17 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Blood and lymphatic system disorders Febrile neutropenia	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus tachycardia	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Blurred vision	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	16.7% 1/6 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 3/6 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Skin infection	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Upper respiratory infection	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Injury, poisoning and procedural complications Bruising	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alanine aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 3/6 • Number of events 5 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Alkaline phosphatase increased	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Aspartate aminotransferase increased	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 2/6 • Number of events 4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Blood bilirubin increased	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cardiac troponin I increased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cholesterol high	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	14.3% 1/7 • Number of events 5 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Creatinine increased	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 2/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 5 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations INR increased	0.00% 0/6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count decreased	66.7% 4/6 • Number of events 12 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 2 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	25.0% 1/4 • Number of events 5 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	42.9% 3/7 • Number of events 8 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Lymphocyte count increased	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	16.7% 1/6 • Number of events 1 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/4 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/7 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Neutrophil count decreased	100.0% 6/6 • Number of events 13 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 2/6 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 6 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	57.1% 4/7 • Number of events 10 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Platelet count decreased	50.0% 3/6 • Number of events 5 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 3/6 • Number of events 3 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	50.0% 2/4 • Number of events 10 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	57.1% 4/7 • Number of events 11 • Adverse events collected over a period of 2 years and 4 months "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.