Trial Outcomes & Findings for Suberoylanilide Hydroxamic Acid in Advanced Solid Tumors (NCT NCT00106626)
NCT ID: NCT00106626
Last Updated: 2009-04-22
Results Overview
MTD was determined by the occurrence of DLTs during the first treatment cycle. DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The dose level is equal to the MTD if \< 2 patients experience a DLT and is also the highest tolerated dose level in the cohort.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
52 participants
Primary outcome timeframe
Cycle 1 (21 days)
Results posted on
2009-04-22
Participant Flow
First Patient In = 29-Aug-05. Last Patient Last Visit = 03-Dec-07. Multicenter (4 Outpatient Clinics) in US.
Post-group assignment information: For all cohorts doses were administered in repeated 21-day cycles. Determination of the Maximum Tolerated Dose (MTD), by using dose-escalating design and measured by Dose Limiting Toxicity (DLT) is a standard procedure in the development of chemotherapeutic combinations.
Participant milestones
| Measure |
Cohort A - Vorinostat BID + Pemetrexed + Cisplatin
Dose level A.1 - Vorinostat 200 mg twice daily (BID) for 14 days out of 3 weeks + Pemetrexed + Cisplatin
Dose level A.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed + Cisplatin
|
Cohort B - Vorinostat QD + Pemetrexed + Cisplatin
Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
Dose level B.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Cohort C - Vorinostat BID + Pemetrexed
Dose level C.1 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed
Dose level C.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first two weeks, one week off + Pemetrexed
Dose level C.3 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days repeated weekly + Pemetrexed
|
Cohort D - Vorinostat QD + Pemetrexed
Dose level D.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed
Dose level D.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
13
|
9
|
14
|
16
|
|
Overall Study
COMPLETED
|
3
|
3
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
10
|
6
|
12
|
13
|
Reasons for withdrawal
| Measure |
Cohort A - Vorinostat BID + Pemetrexed + Cisplatin
Dose level A.1 - Vorinostat 200 mg twice daily (BID) for 14 days out of 3 weeks + Pemetrexed + Cisplatin
Dose level A.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed + Cisplatin
|
Cohort B - Vorinostat QD + Pemetrexed + Cisplatin
Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
Dose level B.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Cohort C - Vorinostat BID + Pemetrexed
Dose level C.1 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed
Dose level C.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first two weeks, one week off + Pemetrexed
Dose level C.3 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days repeated weekly + Pemetrexed
|
Cohort D - Vorinostat QD + Pemetrexed
Dose level D.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed
Dose level D.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
4
|
3
|
3
|
|
Overall Study
Progressive Disease
|
4
|
1
|
9
|
10
|
|
Overall Study
Received radiation on new therapy
|
1
|
0
|
0
|
0
|
|
Overall Study
> 14 day delay in therapy start
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Suberoylanilide Hydroxamic Acid in Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Cohort A - Vorinostat BID + Pemetrexed + Cisplatin
n=13 Participants
Dose level A.1 - Vorinostat 200 mg twice daily (BID) for 14 days out of 3 weeks + Pemetrexed + Cisplatin
Dose level A.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed + Cisplatin
|
Cohort B - Vorinostat QD + Pemetrexed + Cisplatin
n=9 Participants
Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
Dose level B.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Cohort C - Vorinostat BID + Pemetrexed
n=14 Participants
Dose level C.1 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed
Dose level C.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first two weeks, one week off + Pemetrexed
Dose level C.3 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days repeated weekly + Pemetrexed
|
Cohort D - Vorinostat QD + Pemetrexed
n=16 Participants
Dose level D.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed
Dose level D.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed
|
Total
n=52 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age Continuous
|
60.52 years
n=5 Participants
|
58.23 years
n=7 Participants
|
60.09 years
n=5 Participants
|
63.63 years
n=4 Participants
|
61 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
28 Participants
n=21 Participants
|
|
Race/Ethnicity
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Race/Ethnicity
Black
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Race/Ethnicity
European
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Race/Ethnicity
Hispanic American
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
2 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Race/Ethnicity
White
|
12 participants
n=5 Participants
|
6 participants
n=7 Participants
|
14 participants
n=5 Participants
|
12 participants
n=4 Participants
|
44 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (21 days)Population: A total of 52 participants were enrolled in this study. Six were violations pts (1 in Cohort C Dose Level 1, 1 in Cohort C Dose Level 2, 3 in Cohort D Dose Level 1, and 1 in Cohort D Dose Level 2) and were replaced. None of the violations pts had any DLTs in the first cycle of the study.
MTD was determined by the occurrence of DLTs during the first treatment cycle. DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. The dose level is equal to the MTD if \< 2 patients experience a DLT and is also the highest tolerated dose level in the cohort.
Outcome measures
| Measure |
Dose Level A.1
n=6 Participants
(Cohort A) Dose level A.1 - Vorinostat 200 mg twice daily (BID) for 14 days out of 3 weeks + Pemetrexed + Cisplatin
|
Dose Level A.2
n=7 Participants
(Cohort A) Dose level A.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed + Cisplatin
|
Dose Level B.1
n=3 Participants
(Cohort B) Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Dose Level B.2
n=6 Participants
(Cohort B) Dose level B.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Dose Level C.1
n=7 Participants
(Cohort C) Dose level C.1 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed
|
Dose Level C.2
n=4 Participants
(Cohort C) Dose level C.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first two weeks, one week off + Pemetrexed
|
Dose Level C.3
n=3 Participants
(Cohort C) Dose level C.3 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days repeated weekly + Pemetrexed
|
Dose Level D.1
n=9 Participants
(Cohort D) Dose level D.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed
|
Dose Level D.2
n=7 Participants
(Cohort D) Dose level D.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed
|
|---|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
Number (#) of DLT
|
1 Participants
|
3 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
# Participants treated at a dose level <MTD
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
7 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
# Participants treated at a dose level =MTD
|
6 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
9 Participants
|
0 Participants
|
|
Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
# Participants treated at a dose level >MTD
|
0 Participants
|
7 Participants
|
0 Participants
|
6 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Any time during 8 cycle treatment period through 30 days after.Population: All participants. Treated Population includes all participants who received at least one dose and had efficacy measurements at baseline and at least one post baseline treatment.
Number of participants with disease progression (protocol-mandated reason for discontinuation). Disease progression was determined by the principle investigator.
Outcome measures
| Measure |
Dose Level A.1
n=13 Participants
(Cohort A) Dose level A.1 - Vorinostat 200 mg twice daily (BID) for 14 days out of 3 weeks + Pemetrexed + Cisplatin
|
Dose Level A.2
n=9 Participants
(Cohort A) Dose level A.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed + Cisplatin
|
Dose Level B.1
n=14 Participants
(Cohort B) Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Dose Level B.2
n=16 Participants
(Cohort B) Dose level B.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin
|
Dose Level C.1
(Cohort C) Dose level C.1 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first week, two weeks off + Pemetrexed
|
Dose Level C.2
(Cohort C) Dose level C.2 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days in first two weeks, one week off + Pemetrexed
|
Dose Level C.3
(Cohort C) Dose level C.3 - Vorinostat 300 mg twice daily (BID) for 3 consecutive days out of 7 days repeated weekly + Pemetrexed
|
Dose Level D.1
(Cohort D) Dose level D.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed
|
Dose Level D.2
(Cohort D) Dose level D.2 - Vorinostat 400 mg once daily (QD) for 7 days + Pemetrexed
|
|---|---|---|---|---|---|---|---|---|---|
|
Safety and Tolerability as Measured by the Number of Participants With Disease Progression
|
4 Participants
|
1 Participants
|
9 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Senior Vice President, Clinical and Quantitative Sciences
Merck & Co., Inc.
Phone: 1-800-672-6372
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place