Gemcitabine/Nab-Paclitaxel With HIGRT in Resectable Pancreatic Cancer

Not Applicable

Completed

Conditions: Resectable Pancreatic Cancers

Interventions: Drug: Gemcitabine/nab-Paclitaxel
Radiation: Radiation therapy
Other: Sugical resection
Drug: Adjuvant chemotheapy

Registration Number: NCT02318095

Lead Sponsor: Duke University

Brief Summary: This research protocol will evaluate the feasibility of administering neoadjuvant gemcitabine and nab-paclitaxel with hypofractionated, image guided, intensity modulated radiotherapy (HIGRT) in resectable and borderline resectable pancreatic cancer

Detailed Description: Pancreatic cancer is the fourth leading cause of cancer-related death in the United States and accounts for roughly 40,000 deaths each year. Despite the use of neoadjuvant and adjuvant therapies, little progress has been made in the the last three decades, and the search for more efficacious treatment continues.In patients with a good performance status the combination of effective systemic therapy with gemcitabine/nab-paclitaxel and high dose local radiotherapy may improve disease outcomes. This is a prospective, single arm study in patients in newly diagnosed, previously untreated pancreatic cancer who are planned to undergo surgical resection The primary objective of this study is to evaluate the toxicity of a neoadjuvant approach incorporating gemcitabine/nab-paclitaxel and Hypofractionated image guided intensity-modulated radiotherapy (HIGRT) prior to surgical resection. Eligible subjects will recieve standard neoadjuvant gemcitabine and nab-paclitaxel dosing is as follows:Nab-Paclitaxel (125mg/m2) days 1,8,15 every 28 days for 2 cycles Gemcitabine (1000mg/m2) days 1,8,15 every 28 days for 2 cycles followed by HIGRT and surgical resection.

Adjuvant chemotherapy may be given post surgery at the discretion of the treating medical oncologist.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 40

Inclusion Criteria

Patient has signed informed consent and is willing to comply with the protocol
Histologically or cytologically proven adenocarcinoma of the pancreas (within the last 90 days)
Either resectable or borderline resectable as determined on staging imaging (as defined by National Comprehensive Cancer Network [NCCN])
Patient is 18 years or older
Karnofsky performance status 70 or greater
The ANC count ≥ 1500, the platelet count ≥ 100,000 and hemoglobin ≥ 9g/dL
Laboratory values meet the following constraints: Bilirubin less than or equal to 2 mg/dL; AST and ALT less than or equal to 3 x ULN (stenting to improve biliary obstruction is permitted)
No evidence of metastatic disease based on imaging of the chest, abdomen and pelvis.

Exclusion Criteria

Metastatic disease on pretreatment imaging
Prior systemic therapy
Prior abdominal radiation. Any prior radiation must be approved by the Radiation Oncology PI
Previous treatment for pancreatic cancer
Patients with any serious/poorly controlled medical or psychological conditions that would be exacerbated by treatment, would complicate protocol compliance
Pregnant or lactating. Adequate birth control must be used if of child bearing potential per institutional policy. Negative pregnancy test in female patients of child-bearing potential per institutional policy. Post-menopausal women must have had amenorrhea for at least 18 months to be considered non-child bearing
Clinically significant peripheral vascular disease
Presence of active or chronic infection
Clinically significant atherosclerotic cardiovascular disease including patients with New York Heart Class II/III/IV CHF, ventricular arrhythmias requiring medication, myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary artery bypass grafting, angioplasty, cardiac or other vascular stenting within the past 6 months
History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within six months prior to treatment start
History of collagen vascular disease or inflammatory bowel disease (Crohn's or ulcerative colitis)
Current grade 2 or higher peripheral neuropathy
Anticoagulation with warfarin
History of arterial thromboembolic events or symptomatic pulmonary embolism within the past 6 months
Active bleeding diathesis or history of major bleeding, CNS bleeding, or significant hemoptysis within the past 6 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Chemotherapy/radiation/surgery	Sugical resection	This is a single arm prospective study. All eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel, followed by hypofractionated radiation therapy followed by surgical resection. Subjects may receive adjuvant chemotherapy post surgical resection at the clinical discretion of the medical oncologist.
Chemotherapy/radiation/surgery	Adjuvant chemotheapy	This is a single arm prospective study. All eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel, followed by hypofractionated radiation therapy followed by surgical resection. Subjects may receive adjuvant chemotherapy post surgical resection at the clinical discretion of the medical oncologist.
Chemotherapy/radiation/surgery	Gemcitabine/nab-Paclitaxel	This is a single arm prospective study. All eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel, followed by hypofractionated radiation therapy followed by surgical resection. Subjects may receive adjuvant chemotherapy post surgical resection at the clinical discretion of the medical oncologist.
Chemotherapy/radiation/surgery	Radiation therapy	This is a single arm prospective study. All eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel, followed by hypofractionated radiation therapy followed by surgical resection. Subjects may receive adjuvant chemotherapy post surgical resection at the clinical discretion of the medical oncologist.

Primary Outcome Measures

Name	Time	Method
Feasibility as Measured by Number of Participants Who Complete the Neoadjuvant Gemcitabine/Nab-paclitaxel and HIGRT Regimen	approximately 6 months	The neoadjuvant regimen will be considered feasible if (a) the trial can accrue 25 patients in no more than 3 years and (b) if at least 17 of the 25 patients adhere to the neoadjuvant regimen and c) the acute grade 3+ non-hematologic acute toxicity is less than 50% (exclusing fatigue and alopecia).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Grade >/=2 Acute Toxicity	60 days post surgery	CTCAE version 4 will be used for all toxicity assessments. The acute toxicity rate, defined as any non-hematologic grade 2+ toxicity occurring during HIGRT treatment through 60 days post-treatment, will be estimated with its exact 80% confidence interval. Likewise, we will determine the rate of grade 2+ hematologic toxicity occurring during treatment through 60 days post treatment and the proportion of patients requiring treatment breaks longer than 5 days.
Number of Participants Who Underwent Surgical Resection	14-30 days post surgery	Patients who undergo surgical resection will be documented
Number of Participants Who Received an R0 Resection	14-30 days post surgery	Pathologic review will determine if an R0 resection has been performed. R0 resection indicates a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed.