Study of Neoadjuvant Treatment in Patients With Pancreatic Cancer That is Potentially Resectable

Study Overview
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Brief Summary
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Phase II study of neoadjuvant treatment with Gemcitabine, Tarceva and Oxaliplatin followed by chemotherapy with Tarceva and Gemcitabine in patients with pancreatic adenocarcinoma with borderline resectability. The primary objective is to determine the resectability rate of patients with pancreas adenocarcinoma with borderline resectability determined radiologically, treated with Gemcitabine, Tarceva and Oxaliplatin followed by radiotherapy with Gemcitabine and Tarceva.

Detailed Description
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Patients with borderline resectable pancreatic adenocarcinoma are more likely to develop perioperative complications due to the complexity of surgery. In these patients there is also an increased risk of systemic relapse due to the advanced stage of the tumor as well as a higher possibility of having positive margins. Therefore, the treatment of these patients need to be decided based on a multidisciplinary strategy. Besides of that the use of systemic neoadjuvant chemotherapy as induction therapy, followed by sequential chemoradiotherapy is a very attractive therapeutic modality. The neoadjuvant treatment offers the potential advantages of reducing the tumor stage, increasing resectability and decreasing postoperative complications. The administration of chemotherapy and radiotherapy before surgery represent an strategy for early treatment of micrometastatic disease, present in most of these patients, and to identify patients with rapid progression of the disease. For all the reasons above, the investigators consider it's of great interest to design new studies that combine systemic neoadjuvant chemotherapy followed by chemoradiotherapy with neoadjuvant intention in patients with pancreas cancer locally advanced.

Official Title
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Phase II Study of Neoadjuvant Treatment With Gemcitabine, Tarceva and Oxaliplatin Followed by Chemotherapy With Tarceva and Gemcitabine in Patients With Pancreas Adenocarcinoma With Borderline Resectability.

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Radiation: Radiotherapy
* Drug: Tarceva
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Before the beginning of the specific protocol procedures must be obtained and documented a written consent form. Patients must have sufficient capacity to understand and sign the consent form. Exocrine pancreatic potentially resectable carcinoma, histologically confirmed. Aged 18-75 years. OMS functional state (FE) from 0-2 and Karnofsky functional state 70%. Radiologically or measurable disease, defined as borderline resectability disease. Appropriate biological parameters: neutrophils > 1.500/mL; platelets > 100.000/mL; hemoglobin > 10 g/dl.Serum creatinine < 1,5 x upper limit of normal (LSN); alkaline phosphatase < 3 x LSN and bilirubin < 1,5 x LSN; AST and ALT 2,5 x LSN. Controlled biliary obstruction in all the patients before their inclusion in the study. Absence of peripheral neuropathy grade 2. Life expectancy of at least 3 months. Exclusion Criteria: Previous administration of chemotherapy, radiotherapy or any investigational agents for pancreatic cancer treatment. Administration of other experimental treatment during this study or in the previous 6 months. Pregnancy, inappropriate or unsafe use of contraceptive methods or women who are breast-feeding. Clinically significant heart disease(for example: congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not properly controlled with medication or myocardial infarction in the last 12 months). Presence of significant ophthalmologic anomaly, included: severe dry eye syndrome, Sjogren syndrome, dry keratoconjunctivitis, severe exposure keratopathy, conditions that might increase the risk of epithelium complications. Patients with lack of physical integrity of the upper gastrointestinal tract or bad absorption syndromes or unable to ingest the tablets. Other previous bad or concurrent diseases, with the exception of nonmelanoma skin cancer. Medical or psychiatric pathologies that are severe or uncontrolled. Distant metastases.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QT + QRT<br>Chemotherapy (6 cycles x 14 days): Gemcitabine 1000 mg/m2 (day 1) + Oxaliplatin 100 mg/m2 (day 2) + Tarceva 100 mg/day. Chemoradiotherapy (5,5 weeks): Gemcitabine 40 mg/m2 (2 days/week) + Tarceva 100 mg/day + Radiotherapy (1,8 Gy/day x 28 doses, total dose: 50,4 Gy). | Drug: Gemcitabine<br>* 1000mg/m2 / / 40mg/m2<br>* Other names: gemzar;Radiation: Radiotherapy<br>* 50.4 Gy<br>Drug: Tarceva<br>* 100mg/day<br>* Other names: Erlotinib;Drug: Oxaliplatin<br>* 100mg/m2 (only in QT)<br>* Other names: ELOXATIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resectability rate after neoadjuvant treatment with chemotherapy plus chemoradiotherapy. | Determine the resectability rate of subjects with borderline resectable pancreatic cancer (radiologically measured) that were treated with Gemcitabine, Tarceva and Oxaliplatin followed by chemoradiotherapy with Gemcitabine and Tarceva. | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median overall survival. | To determine the overall survival (OS) and the tumor recurrence pattern (local versus distant). | Two years | 
| Rate of resections with engative margins and complete pathological response. | To determine the rate of negative margin resections and complete pathological response (cPR). | Two years | 
| Response rate to neoadjuvant treatment of tumor markers (CEA, CA19-9) | To determine the reponse rate to the neoadjuvant treatment of speficic tumor markers (CEA, Ca19-9). | Two years | 
| Ratio of objective responses (RECIST). | To determine the ratio of objective responses according to RECIST criteria. | Two years | 
| Prognosis accuracy of serum protein profiles | To determine the prognosis accuracy of serum protein profiles in these subjects. | Two years | 
| Viability of the collection of pre-treatment tumor samples | To determine the feasibility of the collection of pre-treatment (baseline) tumor samples and to set pathological correlations with the response after neoadyuvant treatment. | Two years | 
| Adverse events | To determine the safety, toxicity and feasibility of this therapeutical regimen as neoadyuvant treatment. | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant treatment, borderline resectability