Non-small Cell Lung Cancer
Conditions
Keywords
Phase I, Advanced non-small cell lung cancer
Brief summary
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
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.
Interventions
DRUGVorinostat, Bevacizumab, Carboplatin, Paclitaxel
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.
Sponsors
Milton S. Hershey Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | An average of 2 years | Participants will be followed for survival, an expected average of two years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Average of 2 years | Participants will be followed for survival, an expected average of 2 years. |
Countries
United States
Outcome results
None listed