Back to resultsA Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)
Primary Purpose
Carcinoma, Non-Small-Cell Lung
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Vorinostat
Vorinostat
Vorinostat
Vorinostat
erlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Relapsed Non-Small-Cell Lung Cancer, Refractory Non-Small-Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria: Males and females 18 years of age and older with a confirmed diagnosis of non-small-cell lung cancer (NSCLC) who have failed at least one prior treatment for NSCLC. Patients must have proven disease by CT scan or MRI. Patients must be at least 4 weeks from any chemotherapy for cancer or from any surgeries or from any treatment using an investigational drug. Patients must be 2 weeks out from radiation therapy. At screening the patient must have normal lab results and can not be pregnant. Women and men must agree to practice adequate birth control during the study. Patient has the ability to understand and sign the consent form. Exclusion Criteria: Patient had prior treatment with vorinostat or erlotinib. Patient has any of the following conditions: active infections including hepatitis B or C, unstable brain metastases, swallowing difficulties, heart problems, significant eye abnormalities, drug or alcohol abuse, mental illness or pregnancy.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk
Arm Description
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
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.
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.
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.
Outcomes
Primary Outcome Measures
Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study
Adverse event(s) that determined the treatment dose level was not tolerable for that patient in Cycle 1 of the Phase I portion of the study.
Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study
Adverse event(s) that determined the treatment dose level was not tolerable for that patient in Cycle 1 of the Phase II portion of the study.
Secondary Outcome Measures
Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST)
An unconfirmed partial response is defined as a partial response that has not been confirmed by a follow up CT scan (or MRI) at least 4 weeks after the criteria for response are first met. (A partial response is defined as an at least 30% reduction in the sum of the longest diameter of the target lesions. Non-target lesions must be at least stable)
Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)
Stable disease is defined as less than a radiographic partial response, but not progressive disease
Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)
Progressive disease is defined as a ≥20% increase in the sum of the longest diameter, the appearance of one or more new lesions and/or unequivocal progression of non-target lesions by conventional or spiral CT or MRI
Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST)
First documentation of Progressive Disease (PD) occurring > 8 weeks on study.
Progression-free Survival
Progression-free survival was measured from the start of the treatment to the time when the criteria for progression was met or death due to any cause (whichever is first recorded).
Full Information
NCT ID
NCT00251589
First Posted
November 7, 2005
Last Updated
February 17, 2015
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00251589
Brief Title
A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)
Official Title
A Phase I/II Clinical Trial of Oral Vorinostat (MK0683) in Combination With Erlotinib in Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Terminated
Why Stopped
This trial is being closed based on lack of substantive efficacy, slow accrual and overall tolerance in patients treated to date.
Study Start Date
January 2006 (undefined)
Primary Completion Date
October 2007 (Actual)
Study Completion Date
October 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The reason for this study will be to find the safest maximum tolerated dose of oral vorinostat in combination with erlotinib [Tarceva (TM)] that can be given to patients with lung cancer who have relapsed or failed other therapy for the disease. Once the safest maximum tolerated dose of vorinostat is determined, patients enrolled in the clinical trial will continue vorinostat and erlotinib for up to 8 months. Safety and effectiveness will also be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
Relapsed Non-Small-Cell Lung Cancer, Refractory Non-Small-Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Arm Type
Experimental
Arm Description
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
Arm Title
Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Arm Type
Experimental
Arm Description
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.
Arm Title
Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
Arm Type
Experimental
Arm Description
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.
Arm Title
Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
MK0683, Zolinza®
Intervention Description
Vorinostat 200 mg twice a day for 3 days a week.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
MK0683, Zolinza®
Intervention Description
Vorinostat 300 mg once a day for 3 days a week.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
MK0683, Zolinza®
Intervention Description
Vorinostat 300 mg twice a day for 3 days a week.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
MK0683, Zolinza®
Intervention Description
Vorinostat 400 mg once a day for 21 out of 28 days.
Intervention Type
Drug
Intervention Name(s)
erlotinib
Other Intervention Name(s)
Tarceva ®
Intervention Description
erlotinib 150 mg once a day.
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT) Occurring in Cycle 1 of the Phase I Portion of the Study
Description
Adverse event(s) that determined the treatment dose level was not tolerable for that patient 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
Title
Dose Limiting Toxicity Occurring in Cycle 1 of the Phase II Portion of the Study
Description
Adverse event(s) that determined the treatment dose level was not tolerable for that patient 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
Secondary Outcome Measure Information:
Title
Unconfirmed Partial Response (UPR) Based on Response Criteria in Solid Tumors (RECIST)
Description
An unconfirmed partial response is defined as a partial response that has not been confirmed by a follow up CT scan (or MRI) at least 4 weeks after the criteria for response are first met. (A partial response is defined as an at least 30% reduction in the sum of the longest diameter of the target lesions. Non-target lesions must be at least stable)
Time Frame
Every 57 days beginning with Cycle 3, or more frequently if appropriate
Title
Stable Disease (SD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)
Description
Stable disease is defined as less than a radiographic partial response, but not progressive disease
Time Frame
Every 57 days beginning with Cycle 3, or more frequently if appropriate
Title
Progressive Disease (PD) as Best Response Based on Response Criteria in Solid Tumors (RECIST)
Description
Progressive disease is defined as a ≥20% increase in the sum of the longest diameter, the appearance of one or more new lesions and/or unequivocal progression of non-target lesions by conventional or spiral CT or MRI
Time Frame
Every 57 days beginning with Cycle 3, or more frequently if appropriate
Title
Disease Progression After Week 8 Based on Response Criteria in Solid Tumors (RECIST)
Description
First documentation of Progressive Disease (PD) occurring > 8 weeks on study.
Time Frame
Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate
Title
Progression-free Survival
Description
Progression-free survival was measured from the start of the treatment to the time when the criteria for progression was met or death due to any cause (whichever is first recorded).
Time Frame
Day 1 to disease progression or death
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females 18 years of age and older with a confirmed diagnosis of non-small-cell lung cancer (NSCLC) who have failed at least one prior treatment for NSCLC.
Patients must have proven disease by CT scan or MRI.
Patients must be at least 4 weeks from any chemotherapy for cancer or from any surgeries or from any treatment using an investigational drug.
Patients must be 2 weeks out from radiation therapy.
At screening the patient must have normal lab results and can not be pregnant.
Women and men must agree to practice adequate birth control during the study.
Patient has the ability to understand and sign the consent form.
Exclusion Criteria:
Patient had prior treatment with vorinostat or erlotinib.
Patient has any of the following conditions: active infections including hepatitis B or C, unstable brain metastases, swallowing difficulties, heart problems, significant eye abnormalities, drug or alcohol abuse, mental illness or pregnancy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)
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