Phase II Study of NGC-Triple Regimen in Potentially Resectable Pancreatic Cancer Patients

Study Overview
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Brief Summary
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This is a phase II multi-center study of nab-paclitaxel, gemcitabine and cisplatin (NGC triple regimen) as preoperative therapy in potentially resectable pancreatic cancer patients. DISEASE STATE Potentially operable or borderline resectable pancreatic adenocarcinoma as assessed by standard CT criteria and histologically confirmed. Staging by pancreatic protocol, helical abdominal computed tomography (with contrast) or MRI (with contrast) required (endoscopic ultrasound is not required). No evidence of metastatic disease. Lymphadenopathy (defined as nodes measuring >1 cm in short axis) outside the surgical basin (i.e., para-aortic, peri-caval, celiac axis, or distant nodes) is considered M1 (unless nodes are biopsied and are negative, then enrollment can be considered after review with the study PI). Potentially Resectable Pancreatic Cancer No involvement of the celiac artery, common hepatic artery, and superior mesenteric artery (SMA) and, if present, replaced right hepatic artery. No involvement or <180° interface between tumor and vessel wall of the portal vein and/or superior mesenteric vein (SMV-PV) and patent portal vein/splenic vein confluence. For tumors of the body and tail of the pancreas, involvement of the splenic artery and vein of any degree is considered resectable disease. Borderline Resectable Pancreatic Cancer Tumor-vessel interface ≥180° of vessel wall circumference, and/or reconstructible occlusion of the SMV-PV. Tumor-vessel interface <180° of the circumference of the SMA. Tumor-vessel interface <180° of the circumference of the celiac artery. Reconstructible short-segment interface of any degree between tumor and hepatic artery.

Detailed Description
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The purpose of this study is to find out if the study drugs nab-paclitaxel, cisplatin, and gemcitabine given together are safe and effective. The combination of nab-paclitaxel plus gemcitabine has been studied in treating patients with pancreatic cancer, and as of September, 2013 is approved for the treatment of advanced pancreatic cancer. In this study, cisplatin will be added to nab-paclitaxel plus gemcitabine, and tested in people who have not yet had any cancer therapy for the diagnosis of localized pancreatic cancer, as treatment prior to surgery, with the goal of improving response. Another name for nab-paclitaxel is Abraxane®. Nab-paclitaxel contains the same medication as the prescription chemotherapy drug Abraxane®. Nab-paclitaxel is approved by the FDA for the treatment of advanced breast cancer, and in September, 2013 nab-paclitaxel, combined with gemcitabine, was approved by the FDA for the treatment of advanced pancreatic cancer. Cisplatin is approved by the FDA for the treatment of advanced bladder cancer, advanced ovarian cancer, and advanced testicular cancer and other childhood cancers. However, cisplatin is not approved by the FDA for the treatment of advanced pancreatic cancer. Gemcitabine was approved by the FDA in 1996 for the treatment of pancreatic cancer. It is also an approved treatment for ovarian cancer, lung cancer, and breast cancer. Nab-paclitaxel, cisplatin, and gemcitabine will be given weekly for 2 weeks followed by a week of rest, for a total of 3 cycles. A cycle is defined as one set of 3 weeks of chemotherapy treatment. Patients will undergo surgery after a minimum of 3 weeks after Cycle 3 of chemotherapy. Following surgery, patients mayl be treated for up to 3 cycles of this same chemotherapy combination.

Official Title
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Phase II Multi-Center Study of Nab-paclitaxel, Gemcitabine and Cisplatin (NGC-Triple Regimen as Preoperative Therapy in Patients With Potentially Resectable and Borderline Resectable Pancreatic Cancer

Conditions
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Resectable Pancreatic Cancer

Intervention / Treatment
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* Drug: NGC-Triple regimen


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria for the Study Include the Following: Patient has an ECOG performance status PS 0-1. No prior chemotherapy or radiation for pancreatic cancer and no prior exposure to gemcitabine and/or nab-paclitaxel Patient has the following blood counts at baseline: ANC ≥1.5 × 109/L (1500 /mm3) Platelets ≥100 × 109/L; (100,000/mm3) Hgb ≥10 g/dL Patient has the following blood chemistry levels at baseline: AST (SGOT), ALT (SGPT) ≤ 3.0 × upper limit of normal (ULN) Alkaline phosphatase (AP) ≤3.0 X ULN Total bilirubin ≤1.5 or ≤ULN Serum creatinine ≤1.5mg/dL or calculated clearance ≥50 mL/min/1.73 m2 for patients with serum creatinine levels >1.5 mg/dL Patient has acceptable coagulation status as indicated by a PT within normal limits (± 15%) and PTT within normal limits (± 15%) Major Exclusion Criteria include the Following: Patient has locally advanced unresectable pancreatic cancer. Patients aged >75. Histologies other than adenocarcinoma, or any mixed histologies, will NOT be eligible. Patient uses therapeutic Coumadin for a history of pulmonary emboli or DVT. Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy. Patient has known infection with HIV, hepatitis B, or hepatitis C. Patient has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis without removal of an organ) within 4 weeks prior to Day 1 of treatment in this study. Prior chemotherapy or radiation for pancreatic cancer. Prior exposure to gemcitabine and/or nab-paclitaxel. Patient has a history of allergy or hypersensitivity to the study drugs. - -

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
Interventional Model Description: Patients receive 3 cycles of preoperative chemotherapy. The regimen consists of gemcitabine 800 mg/m2, nab-paclitaxel 100 mg/m2 and cisplatin 25 mg/m2 given IV weekly x 2, every 3 weeks (one cycle).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resectable and borderline restable<br>Potentially operable or borderline resectable pancreatic adenocarcinoma as assessed by standard CT criteria and histologically confirmed. Patients receive 3 cycles of preoperative chemotherapy (NGC-triple regimen). The regimen consists of gemcitabine 800 mg/m2, Nab-paclitaxel 100 mg/m2and Cisplatin 25 mg/m2 given IV weekly x 2, every 3 weeks (one cycle). Patients will be evaluated for adjuvant therapy within 12 weeks of surgery which will consist of Nab-paclitaxel, gemcitabine, and Cisplatin IV weekly x 2, every 3 weeks (one cycle) x 3 cycles. | Drug: NGC-Triple regimen<br>* gemcitabine 800 mg/m2; Abraxane (nab-paclitaxel 100 mg/m2; cisplatin 25 mg/m2<br>* Other names: Nab-paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate 2 year survival from date of entry into study | Overall survival of patients as well as 1, and 2 year survivals will be tabulated. | Patients will be followed for survival from Day 1 of treatment with phone calls or review of records on a monthly basis for the first 6 months, and then every 6 months for 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the number and type of treatment-related adverse events as assessed by CTCAE 4.0 | To determine the number and type of treatment-related adverse events as assessed by CTCAE v4.0 | Monitor treatment-related adverse events during neoadjuvant treatment for up to 3 months prior to surgery, and for up to 3 months after surgery. | 
| Histological Response to Pre-Operative Therapy | Grade III/IV histological response to preoperative therapy in resected tumor specimens | Specimens obtained during surgery 3-7 weeks following last dose of chemotherapy; | 
| Radiological Response Rate to Pre-Operative Therapy in the Primary Tumor | Radiological response rate in the primary tumor to preoperative therapy | PET/CT scans performed at Baseline, and immediately prior to surgery, 3-7 weeks following last dose of chemotherapy; | 
| CA 19-9 response to preoperative therapy | CA 19-9 response to preoperative therapy | CA 19-9 evaluation during preoperative therapy once per treatment cycle; | 
| Resectability (RO and R1) Rate Following Preoperative Therapy | Resectability (RO and R1) rate following preoperative therapy in potentially operable or locally advanced patients | Determine RO and R1 resectability rate at surgery, 3-7 weeks following last dose of chemotherapy; | 
| Determine Postoperative Complications of Surgery | Tabulate postoperative complications of surgery | Evaluate surgical complications within 12 weeks post-surgery to determine eligibility for up to 3 cycles (28 days per cycle) of adjuvant treatment | 
| Time to Recurrence | Determine Time to recurrence and patterns of recurrence within the 24 month follow-up period | After Day 1 of treatment, time to recurrence will be collected within the 24 month follow up period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resectable pancreatic cancer, NGC-triple regimen