A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)
February 17, 2015 updated by: Merck Sharp & Dohme LLC
A Phase I/II Clinical Trial of Oral Vorinostat (MK0683) in Combination With Erlotinib in Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
23
Phase
- Phase 2
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Vorinostat 200 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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 200 mg twice a day for 3 days a week.
Other Names:
Vorinostat 300 mg once a day for 3 days a week.
Other Names:
Vorinostat 300 mg twice a day for 3 days a week.
Other Names:
Vorinostat 400 mg once a day for 21 out of 28 days.
Other Names:
erlotinib 150 mg once a day.
Other Names:
|
|
Experimental: Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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 200 mg twice a day for 3 days a week.
Other Names:
Vorinostat 300 mg once a day for 3 days a week.
Other Names:
Vorinostat 300 mg twice a day for 3 days a week.
Other Names:
Vorinostat 400 mg once a day for 21 out of 28 days.
Other Names:
erlotinib 150 mg once a day.
Other Names:
|
|
Experimental: Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk
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 200 mg twice a day for 3 days a week.
Other Names:
Vorinostat 300 mg once a day for 3 days a week.
Other Names:
Vorinostat 300 mg twice a day for 3 days a week.
Other Names:
Vorinostat 400 mg once a day for 21 out of 28 days.
Other Names:
erlotinib 150 mg once a day.
Other Names:
|
|
Experimental: Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk
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.
|
Vorinostat 200 mg twice a day for 3 days a week.
Other Names:
Vorinostat 300 mg once a day for 3 days a week.
Other Names:
Vorinostat 300 mg twice a day for 3 days a week.
Other Names:
Vorinostat 400 mg once a day for 21 out of 28 days.
Other Names:
erlotinib 150 mg once a day.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
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.
|
Day 1 to 28 in the Phase I portion of the study
|
|
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
|
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.
|
Day 1 to 28 in the Phase II portion of the study
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
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
|
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)
|
Every 57 days beginning with Cycle 3, or more frequently if appropriate
|
|
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
|
Stable disease is defined as less than a radiographic partial response, but not progressive disease
|
Every 57 days beginning with Cycle 3, or more frequently if appropriate
|
|
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
|
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
|
Every 57 days beginning with Cycle 3, or more frequently if appropriate
|
|
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
|
First documentation of Progressive Disease (PD) occurring > 8 weeks on study.
|
Every 57 days beginning with Cycle 3 (Week 8), or more frequently if appropriate
|
|
Progression-free Survival
Time Frame: Day 1 to disease progression or death
|
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).
|
Day 1 to disease progression or death
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2006
Primary Completion (Actual)
October 1, 2007
Study Completion (Actual)
October 1, 2007
Study Registration Dates
First Submitted
November 7, 2005
First Submitted That Met QC Criteria
November 8, 2005
First Posted (Estimate)
November 10, 2005
Study Record Updates
Last Update Posted (Estimate)
March 6, 2015
Last Update Submitted That Met QC Criteria
February 17, 2015
Last Verified
February 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Histone Deacetylase Inhibitors
- Erlotinib Hydrochloride
- Vorinostat
Other Study ID Numbers
- 0683-025
- MK0683-025 (Other Identifier: Merck)
- 2005_080 (Other Identifier: Merck)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.