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| Study Type: | Interventional |
|---|---|
| Study Design: | Non-Randomized, Open Label, Uncontrolled, Single Group Assignment |
| Condition: |
Advanced Cancer |
| Intervention: |
Drug: vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]) in combination with Pemetrexed and Cisplatin |
Participant Flow
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| First Patient In = 29-Aug-05. Last Patient Last Visit = 03-Dec-07. Multicenter (4 Outpatient Clinics) in US. |
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
|
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. |
| Description | |
|---|---|
| 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 |
| Cohort A - Vorinostat BID + Pemetrexed + Cisplatin | Cohort B - Vorinostat QD + Pemetrexed + Cisplatin | Cohort C - Vorinostat BID + Pemetrexed | Cohort D - Vorinostat QD + Pemetrexed | |
|---|---|---|---|---|
| STARTED | 13 | 9 | 14 | 16 |
| COMPLETED | 3 | 3 | 2 | 3 |
| NOT COMPLETED | 10 | 6 | 12 | 13 |
| Adverse Event | 5 | 4 | 3 | 3 |
| Progressive Disease | 4 | 1 | 9 | 10 |
| Received radiation on new therapy | 1 | 0 | 0 | 0 |
| > 14 day delay in therapy start | 0 | 1 | 0 | 0 |
Baseline Characteristics
| Description | |
|---|---|
| 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 |
| Cohort A - Vorinostat BID + Pemetrexed + Cisplatin | Cohort B - Vorinostat QD + Pemetrexed + Cisplatin | Cohort C - Vorinostat BID + Pemetrexed | Cohort D - Vorinostat QD + Pemetrexed | Total | |
|---|---|---|---|---|---|
|
Number of Participants [units: participants] |
13 | 9 | 14 | 16 | 52 |
|
Age [units: years] Mean ( Full Range ) |
60.52 ( 35 to 81 ) |
58.23 ( 31 to 74 ) |
60.09 ( 41 to 78 ) |
63.63 ( 39 to 81 ) |
61 ( 31 to 81 ) |
|
Gender [units: participants] |
|||||
| Female | 4 | 5 | 7 | 8 | 24 |
| Male | 9 | 4 | 7 | 8 | 28 |
|
Race/Ethnicity [units: participants] |
|||||
| Asian | 0 | 0 | 0 | 1 | 1 |
| Black | 0 | 2 | 0 | 1 | 3 |
| European | 0 | 1 | 0 | 0 | 1 |
| Hispanic American | 1 | 0 | 0 | 2 | 3 |
| White | 12 | 6 | 14 | 12 | 44 |
Outcome Measures
| 1. Primary: | Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level [ Cycle 1 (21 days) ] |
Hide Outcome Measure 1| Measure Type | Primary |
|---|---|
| Measure Title | Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level |
| Measure Description | 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. |
| Time Frame | Cycle 1 (21 days) |
| Safety Issue | Yes |
| Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. |
|---|
| 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. |
| Description | |
|---|---|
| Dose Level A.1 | (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 | (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 | (Cohort B) Dose level B.1 - Vorinostat 300 mg once daily (QD) for 7 days + Pemetrexed + Cisplatin |
| Dose Level B.2 | (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 |
| Dose Level A.1 | Dose Level A.2 | Dose Level B.1 | Dose Level B.2 | Dose Level C.1 | Dose Level C.2 | Dose Level C.3 | Dose Level D.1 | Dose Level D.2 | |
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants Analyzed
[units: participants] |
6 | 7 | 3 | 6 | 7 | 4 | 3 | 9 | 7 |
|
Maximum Tolerated Dose (MTD) Status as Determined by Number of Participants With Dose Limiting Toxicity (DLT) at Each Dose Level
[units: Participants] |
|||||||||
| Number (#) of DLT | 1 | 3 | 0 | 2 | 1 | 0 | 0 | 1 | 2 |
| # Participants treated at a dose level <MTD | 0 | 0 | 0 | 0 | 7 | 4 | 0 | 0 | 0 |
| # Participants treated at a dose level =MTD | 6 | 0 | 3 | 0 | 0 | 0 | 3 | 9 | 0 |
| # Participants treated at a dose level >MTD | 0 | 7 | 0 | 6 | 0 | 0 | 0 | 0 | 7 |
| 2. Secondary: | Safety and Tolerability as Measured by the Number of Participants With Disease Progression [ Any time during 8 cycle treatment period through 30 days after. ] |
More Information
| All Principal Investigators ARE employed by the organization sponsoring the study. |
| Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data |
|---|
| No text entered. |
| Responsible Party: | Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences ) |
| Study ID Numbers: | 2005_006, MK0683-012 |
| Study First Received: | March 28, 2005 |
| Results First Received: | November 25, 2008 |
| Last Updated: | March 16, 2009 |
| ClinicalTrials.gov Identifier: | NCT00106626 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
