A Phase II Study of Gemcitabine and Erlotinib Plus Sorafenib (GES) in Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 2
- Intervention
- Gemcitabine
- Conditions
- Pancreatic Cancer
- Sponsor
- NYU Langone Health
- Enrollment
- 45
- Locations
- 3
- Primary Endpoint
- 4-month Progression Free Survival (PFS) Rate
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This study tests the combination of two targeted therapies,along with chemotherapy treatment in the treatment of pancreatic cancer.
Detailed Description
Until very recently, additional therapies in pancreatic cancer have targeted either the vascular endothelial growth factor (VEGF) or epidermal growth factor (EGF) pathways, a strategy which has shown variable clinical efficacy. This inconsistency is not surprising, given the knowledge that tumors have a certain level of signal redundancy which may limit the effectiveness of any one single-targeted therapy. The dual blockade of the EGF and VEGF pathways takes aim at two of the most active cascades in tumorigenesis. Preliminarily, a phase II study done in pancreatic cancer with gemcitabine, bevacizumab and erlotinib or cetuximab has shown promising results and will most likely proceed to phase III study for definitive efficacy assessment (Kindler et al, 2006). In this study, targeted blockade is carried one step further with the inhibition of the signaling cascade downstream of receptor tyrosine kinases at the level of raf. Given the fact that the majority of pancreatic tumors display constitutive activation of the Ras/Raf/MEK/ERK pathway, it is hoped that the addition of sorafenib to gemcitabine and erlotinib will obtain a more complete blockade of the signal transduction cascade responsible for pancreatic tumor growth and progression.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery. Patients with locally advanced disease must have disease that extends outside the boundaries of a standard radiation port.
- •Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST). This requires at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan. Pleural effusions and ascites are not considered measurable lesions.
- •No prior cytotoxic chemotherapy for metastatic disease. Prior adjuvant chemotherapy is allowed, however at least 6 months must have elapsed from administration of the last dose of chemotherapy or radiotherapy.
- •No prior therapy with a VEGF, EGFR, or multi-targeted kinase inhibitor.
- •Age \>18 years.
- •Life expectancy of greater than 3 months.
- •Eastern Cooperative Oncology Group performance status 0-
- •Normal organ and marrow function as defined below:
- •White blood cells (WBC) \>3,000/µl
- •Absolute neutrophil count \>1,500/µl
Exclusion Criteria
- •No prior treatment with bevacizumab, cetuximab, or erlotinib. Prior gemcitabine in the adjuvant setting completed more than six months previously will be allowed.
- •No other investigational agents.
- •No central nervous system (CNS) disease, including primary brain tumors, brain metastasis, or history of a cerebro-vascular accident (CVA) or transient ischemic attack (TIA) within 6 months of starting therapy.
- •No allergic reactions to compounds similar to erlotinib or sorafenib.
- •Because an increased risk of bleeding may occur following sorafenib administration, no patients will be allowed with a history of bleeding diathesis or coagulopathy. No grade \> 2 pulmonary hemorrhage or \> grade 3 other hemorrhage within 28 days of beginning therapy.
- •No recent invasive procedures defined as follows: Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 of therapy
- •No Patients with clinically significant cardiovascular disease, defined as:
- •Uncontrolled hypertension
- •Myocardial infarction \< 6 months prior to registration and new onset angina within 3 months (controlled stable angina acceptable)
- •New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris
Arms & Interventions
Combination GES
Combination of Gemcitabine, Erlotinib, and Sorafenib
Intervention: Gemcitabine
Combination GES
Combination of Gemcitabine, Erlotinib, and Sorafenib
Intervention: Erlotinib
Combination GES
Combination of Gemcitabine, Erlotinib, and Sorafenib
Intervention: Sorafenib
Outcomes
Primary Outcomes
4-month Progression Free Survival (PFS) Rate
Time Frame: 4 months
The PFS rate at 4 months is defined as the percentage of patients whose disease is progression free at 4 months from the start of treatment. Disease progression is evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse et al, 2000). Radiological measurements to determine progression is performed every 2 cycles.
Secondary Outcomes
- Objective Response Rate(up to 1 year)
- Median Overall Survival (mOS)(up to 2 years)