A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer
This study has been terminated.
(This trial is being closed based on lack of substantive efficacy, slow accrual and overall tolerance in patients treated to date.)
Sponsor:
Merck
Information provided by:
Merck
ClinicalTrials.gov Identifier:
NCT00251589
First received: November 7, 2005
Last updated: March 9, 2009
Last verified: February 2009
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Results First Received: October 27, 2008
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment |
| Condition: |
Carcinoma, Non-Small-Cell Lung |
| Interventions: |
Drug: Vorinostat Drug: erlotinib |
Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| This study was conducted at 12 investigative sites in the United States. The first patient’s first visit was 30 March 2006. The study was terminated early on 12 Oct 2007 and the last patient’s last visit was 30 Oct 2007. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
| Enrolled patients were assigned to 1 of 2 dose escalating cohorts (A and B) in the Phase I portion of the study to determine the maximum tolerated dose (MTD). Once determined, new patients were assigned to the Phase II portion of the study and treated with the MTD. Active Phase I patients continued into Phase II. |
Reporting Groups
| Description | |
|---|---|
| Cohort B, Dose Level 1; Maximum Tolerated Dose (MTD) | Vorinostat 200 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and determined to be the MTD and therefore the recommended Phase II dose. Of the 16 patients treated at this dose level, 4 were assigned to the Phase I portion of the study and 12 were assigned to the Phase II portion. |
| Cohort A, Dose Level 1 (Amended) | Vorinostat 300 mg once a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the amended study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study. |
| Cohort B, Dose Level 2 | Vorinostat 300 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study. |
| Cohort A, Dose Level 1 (Original) | Vorinostat 400 mg once a day for 21 out of 28 days + erlotinib 150 mg once a day was evaluated in the Phase I portion of the original study and exceeded MTD. This cohort was then amended (Amendment 1) to identify a more tolerable once daily vorinostat dosing regimen. All patients treated at this dose level were assigned to the Phase I portion of the study. |
Participant Flow: Overall Study
| Cohort B, Dose Level 1; Maximum Tolerated Dose (MTD) | Cohort A, Dose Level 1 (Amended) | Cohort B, Dose Level 2 | Cohort A, Dose Level 1 (Original) | |
|---|---|---|---|---|
| STARTED | 16 [1] | 3 | 2 | 2 |
| COMPLETED | 1 | 0 | 0 | 0 |
| NOT COMPLETED | 15 | 3 | 2 | 2 |
| Adverse Event | 5 | 1 | 2 | 1 |
| Withdrawal by Subject | 1 | 1 | 0 | 0 |
| Discontinued due to progressive disease | 9 | 1 | 0 | 1 |
| [1] | 4 of the 16 patients participated in Phase I and II portions. 12 participated in Phase II only. |
|---|
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| Cohort B, Dose Level 1; Maximum Tolerated Dose (MTD) | Vorinostat 200 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and determined to be the MTD and therefore the recommended Phase II dose. Of the 16 patients treated at this dose level, 4 were assigned to the Phase I portion of the study and 12 were assigned to the Phase II portion. |
| Cohort A, Dose Level 1 (Amended) | Vorinostat 300 mg once a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the amended study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study. |
| Cohort B, Dose Level 2 | Vorinostat 300 mg twice a day for 3 days a week + erlotinib 150 mg once a day was evaluated in the Phase I portion of the study and exceeded the MTD. All patients treated at this dose level were assigned to the Phase I portion of the study. |
| Cohort A, Dose Level 1 (Original) | Vorinostat 400 mg once a day for 21 out of 28 days + erlotinib 150 mg once a day was evaluated in the Phase I portion of the original study and exceeded MTD. This cohort was then amended (Amendment 1) to identify a more tolerable once daily vorinostat dosing regimen. All patients treated at this dose level were assigned to the Phase I portion of the study. |
| Total | Total of all reporting groups |
Baseline Measures
| Cohort B, Dose Level 1; Maximum Tolerated Dose (MTD) | Cohort A, Dose Level 1 (Amended) | Cohort B, Dose Level 2 | Cohort A, Dose Level 1 (Original) | Total | |
|---|---|---|---|---|---|
|
Number of Participants
[units: participants] |
16 | 3 | 2 | 2 | 23 |
|
Age
[units: Years] Mean ± Standard Deviation |
53.0 ± 4.36 | 66.0 ± 8.49 | 48.5 ± 20.51 | 59.1 ± 11.59 | 60.7 ± 11.41 |
|
Age, Customized
[units: Participants] |
|||||
| ≤ 65 years | 11 | 3 | 1 | 2 | 17 |
| > 65 years | 5 | 0 | 1 | 0 | 6 |
|
Gender
[units: participants] |
|||||
| Female | 8 | 2 | 1 | 1 | 12 |
| Male | 8 | 1 | 1 | 1 | 11 |
Outcome Measures
| 1. Primary: | Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study [ Time Frame: Day 1 to 28 in the Phase I portion of the study ] |
| 2. Primary: | Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study [ Time Frame: Day 1 to 28 in the Phase II portion of the study ] |
| 3. Secondary: | Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] |
| 4. Secondary: | Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] |
| 5. Secondary: | Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3, or more frequently if appropriate ] |
| 6. Secondary: | Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST) [ Time Frame: Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate ] |
| 7. Secondary: | Progression-free Survival [ Time Frame: Day 1 to disease progression or death ] |
| 8. Post-Hoc: | Dose Limiting Toxicity Occurring in Cycles 2 and Beyond of the Phase II Portion of the Study [ Time Frame: After day 28 in the Phase II portion of the study ] |
More Information
Certain Agreements:
Limitations and Caveats
Results Point of Contact:
No publications provided
| All Principal Investigators ARE employed by the organization sponsoring the study. |
Limitations and Caveats
| 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 |
|---|
| Due to the slow pace of patient accrual, failure to observe meaningful efficacy in treated patients, and overall intolerance of the combination regimen, the study was terminated prematurely on 12-Oct-2007. |
Results Point of Contact:
Name/Title: Senior Vice President, Clinical and Quantitative Sciences
Organization: Merck & Co., Inc.
phone: 1-800-672-6372
Organization: Merck & Co., Inc.
phone: 1-800-672-6372
No publications provided
| Responsible Party: | Executive Vice President, Clinical and Quantitative Sciences, Merck & Co., Inc. |
| ClinicalTrials.gov Identifier: | NCT00251589 History of Changes |
| Other Study ID Numbers: | 2005_080, MK0683-025 |
| Study First Received: | November 7, 2005 |
| Results First Received: | October 27, 2008 |
| Last Updated: | March 9, 2009 |
| Health Authority: | United States: Food and Drug Administration |