A Study of Gemcitabine/Nab-paclitaxel and Radiation Therapy Followed by Surgery in Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This is a phase 1 (the first phase in testing a new drug, to see how safe a new drug or new indication/population ) and phase 2 (the second phase in testing a new drug or new indication/population to see how effective the drug is) study of neoadjuvant (treatment before the main treatment) with gemcitabine and nab-paclitaxel (abraxane) and gemcitabine and radiation therapy before surgery and then gemcitabine and nab-paclitaxel after surgery in patients with pancreatic cancer that has grown to involve one of the major artery branches.

Detailed Description
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Gemcitabine and nab-paclitaxel are chemotherapy drugs that are currently approved by Health Canada for use in combination for the treatment of pancreatic cancer. However, the combination of gemcitabine and nab-paclitaxel as a neoadjuvant treatment prior to gemcitabine and radiation is experimental. Surgery to remove or reconstruct the major artery is also experimental.

Official Title
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A Phase I/II Study Evaluating the Feasibility and Safety of Neoadjuvant Gemcitabine/Nab-paclitaxel (GA) and Concurrent Gemcitabine and Radiation Therapy Followed By Pancreatic Resection and Major Arterial Resection for Adenocarcinoma of the Pancreas (ARCAP) in Patients With Advanced Disease

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Nab-paclitaxel
* Radiation: Radiation Therapy
* Procedure: Surgical Resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Surgical: Medically fit for major pancreatic surgery No evidence of metastases No prior resection Arterial involvement limited to a single major vessel and is resectable Tumour-free margins could be achieved Acceptable length of vessel Mass considered otherwise resectable by current standards General: Less than 70 years old Performance status <=2 Has pancreatic adenocarcinoma Adequate bone marrow and organ function Therapeutic heparin is allowed Taking chronic erythropoietin are permitted Not pregnant Agree to use contraception Able to provide written consent Exclusion Criteria: Surgical: Aortic involvement Involvement of 2 major arterial trunks SMV/portal venous occlusion, cannot be reconstructed Extensive venous involvement, no arterial involvement Disease progression on neo-adjuvant treatme General: Concurrent cancer diagnosis Other malignancies unless all therapy completed, no disease for >=3 years Prior radiotherapy or chemo within 1 year, to pancreas Bone marrow transplant/stem cell rescue Major surgery <4 wks prior Distant metastases Renal dysfunction Pulmonary insufficiency History of cardiac disease Active systemic infection(s) or any other related illnesses Known HIV, HBV, HCV History of solid organ transplant, cardiovascular disease, inflammatory bowel disease, or underlying neuropathy Conditions interfering with patient participation Known or suspected allergy to study drugs Pregnant or breast-feeding Therapeutic coumadin More than or equal to Grade 2 pre-exiting peripheral neuropathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Gemcitabine/Nab-paclitaxel, Radiation and Surgery<br>Gemcitabine (neoadjuvant and adjuvant), intravenously, at a dose of 1000 mg/m2 given over 30-40 minutes, on Day 1 of every 28 day cycle for 2 cycles. Nab-paclitaxel, intravenously, at a dose of 125 mg/m2 given over 30-40 minutes, on Days 1, 8, and 15 of every 28 day cycle for 2 cycles. Radiation Therapy: 50.4 Gy in 28 fractions (1.8 Gy/fraction) Surgery: Tumor resection and arterial resection/reconstruction | Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Nab-paclitaxel<br> <br> * Other names: Abraxane;Radiation: Radiation Therapy<br> <br> Procedure: Surgical Resection<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type and the severity of side effects |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of surviving patients at 1 year after treatment |  | 1 year | 
| Number of patients who disease has not progressed |  | 2 years | 
| Number of patients that are able to receive surgery after chemoradiation |  | 5 years | 
| Average length of hospital stay per patient |  | 5 years | 
| Number of surviving patients at 30-days after surgery |  | 30 days after surgery | 
| Number of surviving patients at 90-days after surgery |  | 90 days after surgery | 
| Number of patients who need to be re-admitted to the hospital at 90-days after surgery |  | 90 days after surgery | 
| Time to Progression |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Vessels, Reconstructive Surgery