Trial Outcomes & Findings for Vorinostat (MK-0683) Phase I Study in Cutaneous T-Cell Lymphoma (CTCL) Patients (MK-0683-089 EXT1) (NCT NCT00771472)
NCT ID: NCT00771472
Last Updated: 2015-04-21
Results Overview
A laboratory AE is defined as any unfavorable \& unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
10 participants
Primary outcome timeframe
Day 1 up until 30 days post study completion or early termination (up to approximately 506 days)
Results posted on
2015-04-21
Participant Flow
Participant milestones
| Measure |
Part I
Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.
|
Part II
Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
4
|
Reasons for withdrawal
| Measure |
Part I
Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.
|
Part II
Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|---|
|
Overall Study
Physician Decision
|
2
|
3
|
|
Overall Study
Progressive Disease
|
3
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
Baseline Characteristics
Vorinostat (MK-0683) Phase I Study in Cutaneous T-Cell Lymphoma (CTCL) Patients (MK-0683-089 EXT1)
Baseline characteristics by cohort
| Measure |
Vorinostat
n=10 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 12.0 • n=93 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=93 Participants
|
|
Region of Enrollment
Japan
|
10 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Day 1 up until 30 days post study completion or early termination (up to approximately 506 days)A laboratory AE is defined as any unfavorable \& unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body.
Outcome measures
| Measure |
Vorinostat
n=10 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE)
Clinical AEs
|
10 participants
|
|
Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE)
Laboratory AEs
|
6 participants
|
PRIMARY outcome
Timeframe: Day 1 to Day 28A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events \[CTCAE\] version 3.0): * Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC * Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment * Grade 4 neutropenia lasting at least 5 days * Grade 4 thrombocytopenia * Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator * Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies
Outcome measures
| Measure |
Vorinostat
n=6 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT)
|
1 participants
|
SECONDARY outcome
Timeframe: Days 1 & 28 of Cycle 1Population: Number of participants with samples at the specified time point
Blood samples taken as follows: Day 1 \& Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Outcome measures
| Measure |
Vorinostat
n=6 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours])
Day 1 (n=6)
|
4.59 µM*hr
Standard Deviation 2.34
|
|
Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours])
Day 28 (n=5)
|
5.59 µM*hr
Standard Deviation 1.24
|
SECONDARY outcome
Timeframe: Days 1 & 28 of Cycle 1Population: Number of participants with samples at the specified time point
Blood samples taken as follows: Day 1 \& Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Outcome measures
| Measure |
Vorinostat
n=6 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Part I: Maximum Drug Concentration (Cmax)
Day 1 (n=6)
|
0.83 µM
Standard Deviation 0.37
|
|
Part I: Maximum Drug Concentration (Cmax)
Day 28 (n=5)
|
1.17 µM
Standard Deviation 0.37
|
SECONDARY outcome
Timeframe: Days 1 & 28 of Cycle 1Population: Number of participants with samples at the specified time point
Blood samples taken as follows: Day 1 \& Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Outcome measures
| Measure |
Vorinostat
n=6 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Part I: Time at Which Cmax Occurs (Tmax)
Day 1 (n=6)
|
2.91 hours
Interval 2.0 to 6.0
|
|
Part I: Time at Which Cmax Occurs (Tmax)
Day 28 (n=5)
|
3.73 hours
Interval 2.93 to 4.28
|
SECONDARY outcome
Timeframe: Days 1 & 28 of Cycle 1Population: Number of participants with samples at the specified time point
Blood samples taken as follows: Day 1 \& Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Outcome measures
| Measure |
Vorinostat
n=6 Participants
Parts I \& II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2)
Day 1 (n=5)
|
1.94 hours
Standard Deviation 1.30
|
|
Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2)
Day 28 (n=4)
|
2.30 hours
Standard Deviation 1.10
|
Adverse Events
Vorinostat
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat
n=10 participants at risk
Parts I \& II: vorinostat(400 mg) Oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Cellulitis streptococcal
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Infection
|
20.0%
2/10 • Number of events 2
|
Other adverse events
| Measure |
Vorinostat
n=10 participants at risk
Parts I \& II: vorinostat(400 mg) Oral, daily (QD). Treatment period was 28 days per cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
30.0%
3/10 • Number of events 3
|
|
Blood and lymphatic system disorders
Erythropenia
|
10.0%
1/10 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukocytosis
|
10.0%
1/10 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
30.0%
3/10 • Number of events 7
|
|
Blood and lymphatic system disorders
Lymphopenia
|
20.0%
2/10 • Number of events 3
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.0%
1/10 • Number of events 2
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
80.0%
8/10 • Number of events 29
|
|
Cardiac disorders
Atrial fibrillation
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Conjunctivitis
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Vitreous floaters
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
20.0%
2/10 • Number of events 3
|
|
Gastrointestinal disorders
Cheilitis
|
20.0%
2/10 • Number of events 4
|
|
Gastrointestinal disorders
Constipation
|
30.0%
3/10 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
40.0%
4/10 • Number of events 5
|
|
Gastrointestinal disorders
Dry mouth
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Dyspepsia
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
60.0%
6/10 • Number of events 16
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
4/10 • Number of events 7
|
|
General disorders
Chills
|
10.0%
1/10 • Number of events 2
|
|
General disorders
Fatigue
|
40.0%
4/10 • Number of events 6
|
|
General disorders
Malaise
|
50.0%
5/10 • Number of events 10
|
|
General disorders
Oedema peripheral
|
20.0%
2/10 • Number of events 2
|
|
General disorders
Pyrexia
|
40.0%
4/10 • Number of events 9
|
|
General disorders
Swelling
|
10.0%
1/10 • Number of events 1
|
|
Hepatobiliary disorders
Cholecystitis acute
|
10.0%
1/10 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
10.0%
1/10 • Number of events 1
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
20.0%
2/10 • Number of events 3
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
30.0%
3/10 • Number of events 14
|
|
Infections and infestations
Bacterial infection
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Body tinea
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Candidiasis
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Infection
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Keratitis herpetic
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Oral candidiasis
|
10.0%
1/10 • Number of events 1
|
|
Infections and infestations
Viral infection
|
10.0%
1/10 • Number of events 1
|
|
Injury, poisoning and procedural complications
Contusion
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
10.0%
1/10 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
2/10 • Number of events 5
|
|
Investigations
Blood alkaline phosphatase increased
|
10.0%
1/10 • Number of events 2
|
|
Investigations
Blood cholinesterase increased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Blood creatinine increased
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Blood fibrinogen increased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Blood lactate dehydrogenase increased
|
10.0%
1/10 • Number of events 3
|
|
Investigations
Blood urea increased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
C-reactive protein increased
|
10.0%
1/10 • Number of events 2
|
|
Investigations
Fibrin D dimer increased
|
10.0%
1/10 • Number of events 2
|
|
Investigations
Gamma-glutamyltransferase increased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Haemoglobin decreased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Lymphocyte count decreased
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Platelet count decreased
|
10.0%
1/10 • Number of events 2
|
|
Investigations
Prothrombin time shortened
|
10.0%
1/10 • Number of events 1
|
|
Investigations
Weight decreased
|
30.0%
3/10 • Number of events 3
|
|
Metabolism and nutrition disorders
Anorexia
|
60.0%
6/10 • Number of events 11
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
2/10 • Number of events 2
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
30.0%
3/10 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
30.0%
3/10 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
40.0%
4/10 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
20.0%
2/10 • Number of events 3
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
40.0%
4/10 • Number of events 7
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
50.0%
5/10 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Hypercreatinaemia
|
20.0%
2/10 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.0%
1/10 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Ageusia
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Dizziness postural
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
40.0%
4/10 • Number of events 5
|
|
Nervous system disorders
Headache
|
30.0%
3/10 • Number of events 5
|
|
Nervous system disorders
Hypoaesthesia
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Lethargy
|
20.0%
2/10 • Number of events 2
|
|
Nervous system disorders
Somnolence
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Dysuria
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Haemoglobinuria
|
20.0%
2/10 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
40.0%
4/10 • Number of events 4
|
|
Renal and urinary disorders
Renal impairment
|
20.0%
2/10 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.0%
1/10 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Hypertension
|
20.0%
2/10 • Number of events 12
|
|
Vascular disorders
Hypotension
|
10.0%
1/10 • Number of events 1
|
|
Vascular disorders
Lymphoedema
|
10.0%
1/10 • Number of events 1
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER