Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The primary objective of the study is to establish the phase II recommended dose of Vorinostat when administered in combination with the regimen of carboplatin, paclitaxel and bevacizumab for patients with previously untreated advanced non-small cell lunc cancer.

Detailed Description
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Since the regimen of bevacizumab, carboplatin and paclitaxel has become a standard regimen for the treatment of advanced non-squamous NSCLC, new studies in this patient population will have to include this as a reference arm. Addition of a fourth anti-cancer agent has now become the new strategy to improve the outcome for advanced non-squamous NSCLC. Since the regimen of Vorinostat, Carboplatin and Paclitaxel is already in advanced stage of development it is important to study the safety and tolerability of Vorinostat in combination with the three-drug regimen of Bevacizumab, Carboplatin and Paclitaxel. Therefore, we will evaluate Vorinostat when administered in combination with the regimen of Carboplatin, Paclitaxel and Bevacizumab for patients with previously untreated advanced non-small cell lung cancer.

Official Title
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Phase I Study of Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel
* Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced non-squamous NSCLC No prior chemotherapy for advanced disease ECOG performance status 0 or 1 Measurable disease Life expectancy > 3 months Normal bone marrow, renal and hepatic function Ability to take oral medications Willingness to sign informed consent Exclusion Criteria: History of brain metastasis Evidence of thromboembolic phenomenon and treatment with anticoagulants Pregnancy Uncontrolled inter-current illness Prior therapy with Paclitaxel

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Phase I dose escalating scheme | Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel<br>* This dose escalating phase will enroll sequential cohorts of 3-6 patients to be entered at the following dose levels: Level -1: Days 1-14, Vorinostat 100 mg po QD; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 175 mg/m2. Level 1: Days 1-14, Vorinostat 200 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 2: Days 1-14, Vorinostat 300 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 3: Days 1-14, Vorinostat 400 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Treatment cycles will be repeated every 3 weeks. The highest dose level which <2 out of 5 patients experience dose limiting toxicity will be defined as the recommended phase II dose.<br>* Other names: SAHA;|
| Experimental: 2<br>Phase 2 will evaluate the toxicities and safety profile of the 4-drug regimen. | Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel<br>* Once the recommended phase II dose has been established from Phase I, 12 additional patients will be treated to evaluate the toxicities and safety profile of the 4-drug regimen.<br>* Other names: SAHA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the phase II recommended dose (P2RD) of Vorinostat when administered in combination with the regimen of carboplatin, paclitaxel and bevacizumab for patients with previously untreated advanced non-small cell lung cancer. | Participants will be followed for survival, an expected average of two years. | An average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety profile of 4-drug regimen. Obtain preliminary evidence regarding anti-cancer activity of the regimen. Understand mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood and archived tumor tissue. | Participants will be followed for survival, an expected average of 2 years. | Average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Advanced non-small cell lung cancer