Gemcitabine/Nab-Paclitaxel With HIGRT in Resectable Pancreatic Cancer

Feasibility Study of Neoadjuvant Gemcitabine/Nab-Paclitaxel and Hypofractionated Image-Guided Intensity Modulated Radiotherapy in Resectable and Borderline Resectable Pancreatic Cancer

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

Study Overview

• Status: Completed
• Conditions: Resectable Pancreatic Cancers
• Intervention / Treatment: Drug: Gemcitabine/nab-Paclitaxel; Radiation: Radiation therapy; Other: Sugical resection; Drug: Adjuvant chemotheapy

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient has signed informed consent and is willing to comply with the protocol
2. Histologically or cytologically proven adenocarcinoma of the pancreas (within the last 90 days)
3. Either resectable or borderline resectable as determined on staging imaging (as defined by National Comprehensive Cancer Network [NCCN])
4. Patient is 18 years or older
5. Karnofsky performance status 70 or greater
6. The ANC count ≥ 1500, the platelet count ≥ 100,000 and hemoglobin ≥ 9g/dL
7. 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)
8. No evidence of metastatic disease based on imaging of the chest, abdomen and pelvis.

Exclusion Criteria:

1. Metastatic disease on pretreatment imaging
2. Prior systemic therapy
3. Prior abdominal radiation. Any prior radiation must be approved by the Radiation Oncology PI
4. Previous treatment for pancreatic cancer
5. Patients with any serious/poorly controlled medical or psychological conditions that would be exacerbated by treatment, would complicate protocol compliance
6. 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
7. Clinically significant peripheral vascular disease
8. Presence of active or chronic infection
9. 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
10. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within six months prior to treatment start
11. History of collagen vascular disease or inflammatory bowel disease (Crohn's or ulcerative colitis)
12. Current grade 2 or higher peripheral neuropathy
13. Anticoagulation with warfarin
14. History of arterial thromboembolic events or symptomatic pulmonary embolism within the past 6 months
15. Active bleeding diathesis or history of major bleeding, CNS bleeding, or significant hemoptysis within the past 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Chemotherapy/radiation/surgery; 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.

Drug: Gemcitabine/nab-Paclitaxel; Prospective, single arm study ; eligible subjects will recieve 2 cycles of neoadjuvant Gemcitabine/nab-Paclitaxel. All chemotherapy administered to study subjects is standard of care. The chemotherapy combination, gemcitabine/nab-paclitaxel, is considered to be a standard-of-care, non-investigational chemotherapy combination; chemotherapy dosing and treatment schedule will be managed by the treating medical oncologist. Restaging will be completed post chemotherapy.; Radiation: Radiation therapy; 5 fractions of hypofractionated IGRT or IMRT at 5Gy per fraction will be delivered before surgery. Restaging will be completed post radiation therapy.; Other: Sugical resection; Surgical resection of the pancreas post radiation therapy; Drug: Adjuvant chemotheapy; Adjuvant chemotherapy may be given after surgery at the clinical discretion of the medical oncologist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as Measured by Number of Participants Who Complete the Neoadjuvant Gemcitabine/Nab-paclitaxel and HIGRT Regimen	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).	approximately 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Grade >/=2 Acute Toxicity	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.	60 days post surgery
Number of Participants Who Underwent Surgical Resection	Patients who undergo surgical resection will be documented	14-30 days post surgery
Number of Participants Who Received an R0 Resection	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.	14-30 days post surgery

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Manisha Palta, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2015
• Primary Completion (Actual): November 7, 2018
• Study Completion (Actual): November 14, 2022

Study Registration Dates

• First Submitted: December 12, 2014
• First Submitted That Met QC Criteria: December 12, 2014
• First Posted (Estimated): December 17, 2014

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cancer of the pancreas
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Gemcitabine
• Other Study ID Numbers: Pro00058865

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No