Trial Outcomes & Findings for Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma (NCT NCT00121225)

Last Updated: 2019-01-29

Results Overview

Per Response Evaluation Criteria in Solid Tumours Criteria (RECIST v1.0) for target lesions and are assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least 30% decrease in sum of longest diameter of target lesions; Objective Response (OR) = CR+ PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

Up to 5 years

Results posted on

2019-01-29

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1 Vorinostat Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Overall Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vorinostat in Treating Patients With Metastatic or Unresectable Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I n=32 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Age, Continuous	61 years n=93 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=93 Participants
Age, Categorical >=65 years	13 Participants n=93 Participants
Sex: Female, Male Female	12 Participants n=93 Participants
Sex: Female, Male Male	20 Participants n=93 Participants
Region of Enrollment United States	13 participants n=93 Participants
Region of Enrollment Canada	19 participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Arm I n=32 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Objective Response Rate Assessed by Response Evaluation Criteria for Solid Tumors (RECIST)	2 participants

SECONDARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome measures
Measure	Arm I n=32 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Time to Progression Assessed by RECIST	4 months Interval 1.8 to 4.0

SECONDARY outcome

Timeframe: Baseline and day 15

Population: Patient 32 had pre-treatment punch biopsy that was inadequate for testing, thus was not included in this measurement

Macro H2A and HP1 expression levels were compared through analysis of log fold changes in antibody expression in a multivariate general linear model between progressive disease and stable disease outcomes.

Outcome measures

Outcome measures
Measure	Arm I n=31 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes MacroH2A1.2	-0.748 log fold change Standard Error 0.466
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes HP1	-0.077 log fold change Standard Error 0.395
Difference in HP1 and MacroH2A Nuclear Foci Expression Between Progressive Minus Stable Disease Outcomes MacroH2A1.1	0.149 log fold change Standard Error 0.364

SECONDARY outcome

Timeframe: Baseline

Population: Participant 32 had a pre-treatment punch biopsy that was not adequate for testing

Participants were assessed for p53 allelic variation at baseline

Outcome measures

Outcome measures
Measure	Arm I n=31 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Number of Patients With p53 Allelic Variations (72R or 72P) Wild Type	20 participants
Number of Patients With p53 Allelic Variations (72R or 72P) Mutant	11 participants

SECONDARY outcome

Timeframe: Baseline, Day 1, Day 8 and Day 15

Blood specimens were collected from participants on Day 1 Cycle 1 prior to treatment (baseline), Day 1 3-4 hours following Vorinostat ingestion, Day 8 and Day 15. VEGF serum concentrations were detected using the Luminex multiplexed assay, where the median fluorescence intensity results were analyzed by a weighted five-parameter logistic method. The values were averaged across all time points per participant.

Outcome measures

Outcome measures
Measure	Arm I n=32 Participants Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Comparison of VEGF Serum Levels to Response to Vorinostat	203 pg Standard Deviation 0.029

Adverse Events

Arm I

Serious events: 9 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I n=32 participants at risk Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
Gastrointestinal disorders Dry mouth	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Nervous system disorders Dizziness	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Musculoskeletal and connective tissue disorders Back pain	6.2% 2/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Investigations Platelet count decreased	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 2/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Musculoskeletal and connective tissue disorders Myalgia	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Blood and lymphatic system disorders Anemia	6.2% 2/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Metabolism and nutrition disorders Anorexia	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Metabolism and nutrition disorders Hypokalemia	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Vascular disorders Vascular disorders - Other, specify	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Vascular disorders Thromboembolic event	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Renal and urinary disorders Acute kidney injury	6.2% 2/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Metabolism and nutrition disorders Dehydration	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Nervous system disorders Intracranial hemorrhage	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Metabolism and nutrition disorders Hyperglycemia	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Gastrointestinal disorders Gastric hemorrhage	3.1% 1/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.

Other adverse events

Other adverse events
Measure	Arm I n=32 participants at risk Patients will receive vorinostat by mouth once a day for 4 weeks. Treatment may repeat every 4 weeks for as long as benefit is shown. Patients will be evaluated for 4 weeks and every 3 months thereafter. vorinostat
General disorders Fatigue	87.5% 28/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Metabolism and nutrition disorders Hyperglycemia	75.0% 24/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.
Blood and lymphatic system disorders Anemia	62.5% 20/32 Indicates events were collected by systematic assessment and are reported regardless of attribution to agent.

Additional Information

Dr. David Hogg

Princess Margaret Cancer Centre

Phone: 416-946-4501

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60