A Phase I/II Clinical Trial of Vorinostat in Combination With Erlotinib for Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer (0683-025)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I/II Clinical Trial of Oral Vorinostat (MK0683) in Combination With Erlotinib in Patients With Relapsed/Refractory Non-Small-Cell Lung Cancer

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Vorinostat
* Drug: Vorinostat
* Drug: Vorinostat
* Drug: Vorinostat
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention 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<br>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 | Drug: Vorinostat<br>* Vorinostat 200 mg twice a day for 3 days a week.<br>* Other names: Zolinza®;Drug: erlotinib<br>* erlotinib 150 mg once a day.<br>* Other names: Tarceva ®;|
| Experimental: Vorinostat 300 mg q.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk<br>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. | Drug: Vorinostat<br>* Vorinostat 300 mg once a day for 3 days a week.<br>* Other names: Zolinza®;Drug: erlotinib<br>* erlotinib 150 mg once a day.<br>* Other names: Tarceva ®;|
| Experimental: Vorinostat 300 mg b.i.d. 3d/wk + Erlotinib 150 mg q.d. 7d/wk<br>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. | Drug: Vorinostat<br>* Vorinostat 300 mg twice a day for 3 days a week.<br>* Other names: Zolinza®;Drug: erlotinib<br>* erlotinib 150 mg once a day.<br>* Other names: Tarceva ®;|
| Experimental: Vorinostat 400 mg q.d. 21d/4wk + Erlotinib 150 mg q.d. 7d/wk<br>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. | Drug: Vorinostat<br>* Vorinostat 400 mg once a day for 21 out of 28 days.<br>* Other names: Zolinza®;Drug: erlotinib<br>* erlotinib 150 mg once a day.<br>* Other names: Tarceva ®;|

What is the study measuring?
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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 | 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 | 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) | 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) | 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) | 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) | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsed Non-Small-Cell Lung Cancer, Refractory Non-Small-Cell Lung Cancer