Neoadjuvant Therapy Followed by Stereotactic Body Radiotherapy (SBRT) for Locally Advanced Pancreatic Cancer

Pancreas Cancer Clinical Trial

Official title:

A Single Center Pilot Study: Neoadjuvant Modified FOLFIRINOX or Gemcitabine-nab Paclitaxel Followed by Stereotactic Body Radiotherapy (SBRT) for Patients With Locally Advanced Pancreatic Cancer and Borderline Pancreatic Inoperable Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03641183
• Other study ID #: IRB00339168
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 1, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: August 2018
• Source: University of Alabama at Birmingham
• Contact: Ravikumar Paluri, MD
• Phone: 205-934-2992
• Email: drravi[@]uab.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate a new treatment routine for patients with borderline resectable and unresectable pancreas cancers.

Description:

We want to find out what effects, good and bad, using chemotherapy combinations modified FOLFIRINOX (Oxaliplatin, Irinotecan, and fluorouracil) OR gemcitabine plus nab-paclitaxel (Gem-ABRAXANE) and radiation using Stereotactic Body Radiation Therapy (SBRT) have on the cancer and to increase the percentage of patients who can have surgery to remove their disease. SBRT is a short course of high dose precisely delivered radiation. The two combination chemotherapy routines (mFOLFIRINOX or GEM-ABRAXANE) have been shown in previous clinical trials to be the most effective FDA approved chemotherapy in wide spread pancreatic cancers. These chemotherapy drugs will be given before the surgery. Radiation Therapy, using the 5 ½ week method as well as SBRT has been used as standard of care and found to be effective to reduce the size of pancreatic cancer, so patients can have surgery.

SBRT uses advance techniques to deliver radiation therapy which minimizes the volume of normal tissue receiving high dose radiation while maximizing the dose to the tumor. The use of SBRT spares normal tissue and reduces the side effects of radiation. By being more precise, and using a higher dose of radiation per treatment, the radiation delivery time can be decreased to about one week. When this chemotherapy followed by SBRT is combined in this order, this routine has the potential to treat both the primary disease, as well as to prevent the early spread of disease. It is hoped that the treatment routines in this study will increase the percentage of patients who can proceed to have surgery to remove their tumor.

This combination of chemotherapy drugs, mFOLFIRINOX or GEM-ABRAXANE and the sequence of chemotherapy followed by SBRT- the shorter course of radiation has not been studied previously and is considered investigational.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically proven adenocarcinoma of the pancreas. Patients with mixed tumor with predominant adenocarcinoma pathology can be enrolled

• Subjects will be staged according to the 2010 American Joint Committee on Cancer (AJCC) staging system with pathologic stage T1-4, being eligible; and have a primary tumor of the pancreas (either pancreatic head, neck, uncinate process, or body/tail)

• The tumor must be deemed as being borderline/unresectable. Final CT confirmation of surgical staging/eligibility will be at the discretion of the pancreatic surgeon of the patient

• Disease must be confined to loco-regional site as confirmed by CT imaging and / or diagnostic staging laparoscopy to avoid occult peritoneal deposits Diagnostic laparoscopy will be performed only if absolutely required

• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) on imaging studies CT

• Karnofsky performance status greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance of 0-2

• Age > 18

• Estimated life expectance > 12 weeks

• If female patient is of child bearing potential, she must have a negative serum pregnancy test (ßhCG) documented up to 72hrs prior to administration of first study drug

• Patient has screening blood work performed which includes the following (should be drawn = 14 days prior to enrollment):

• Absolute neutrophil count (ANC) > 1.5 x 109/L

• Platelet count = 100000/mm3

• Hemoglobin (HgB) = 9g/dL

• Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT)= 2.5 x upper limit of normal (ULN) Total Bilirubin = 1.5 ULN

• Serum Cr within normal limits (WNL)

• Prothrombin Time and International Normalized Ratio (PT/INR) and Partial Thromboplastin Time (PTT) within normal limits (±15%).

• Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist

Exclusion Criteria:

• Ineligible Histology including non-adenocarcinomas, adenosquamous carcinoma, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct and ampullary carcinomas

• Patients must not have received prior pancreatic surgery, radiation therapy, chemotherapy or any investigational therapy for pancreatic cancer

• Patients with tumors extending or invading duodenum or gastric are not eligible

• Evidence of distant metastasis on upright chest x-ray, CT or other staging studies

• Subjects with recurrent disease are not eligible

• Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment

• Patients with scleroderma, ulcerative colitis or other systemic conditions deemed risky for radiation treatment. Therefore, will be excluded.

• Prior chemotherapy

• Subjects in their reproductive age who are breast feeding or have a positive pregnancy test

• Any co-morbid condition such as but not limited to congestive heart failure, cardiac arrhythmia or psychiatric illness of sufficient severity to limit full compliance with the protocol per assessment by the individual treating physician

• Concurrent active infection

• No prior malignancy allowed except cervical cancer in situ, adequately treated basal cell or squamous cell carcinoma of skin or treated low risk prostate cancer

• Patient with known historical or active infection with HIV, Hepatitis B or Hepatitis C

• Patient who has undergone recent major surgery, other than diagnostic prior to enrollment

• Patient who has a history of allergy or hypersensitivity to any of the study drugs

• Patients with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, interstitial pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies

• Patients with greater than grade 2 peripheral neuropathy at the time of enrollment are not eligible

Related Conditions & MeSH terms

• Pancreas Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• FOLFIRINOX Drugs
Neoadjuvant chemotherapy followed by SBRT in locally advanced pancreatic cancer (LAPC)
• Gemcitabine-nab Paclitaxel
This combination currently considered the standard of care: Neoadjuvant chemotherapy followed by SBRT in locally advanced pancreatic cancer (LAPC)

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the incidence of treatment related adverse effects associated with neoadjuvant chemotherapy followed by stereotactic body radiotherapy (SBRT).	All AEs spontaneously reported by the patient and/or in response to an open question from study personnel or revealed by observation and/or physical examination. The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized. Clinical AEs will be graded on a 3-point scale: Grade 1: Mild, does not require medical intervention, Grade 2: Moderate, the event requires medical intervention, but does not have permanent residual effects, Grades 3-4: Severe, the event is fatal or life-threatening, requires or prolongs inpatient hospitalization, or causes congenital malformations, malignancy, significant disability or incapacity.	From baseline through 36 months
Secondary	To estimate PFS (progression free survival) for all patients	Patients will have follow-ups or surveillance visits every 3 months for the next two years. The following will be performed at surveillance visits and are considered standard of care for cancer patients: 1) Medical History Update, 2) Physical examination to include vital signs, 3) Tumor assessments as per standard of care.The patients will be followed for PFS and OS. Progression-free survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever comes first. Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	From baseline through 36 months
Secondary	To evaluate the rate of preoperative chemo radiotherapy completion	Percentage of patients able to complete the preoperative chemo and radiotherapy.	From baseline through 36 months
Secondary	To estimate the proportion of patients undergoing surgery after preoperative chemoradiation therapy	to assess the proportion of patients able to undergo surgery after completing the preoperative chemo radiotherapy.	From baseline through 36 months
Secondary	To estimate OS (overall survival) for all patients	Patients will have follow-ups or surveillance visits every 3 months for the next two years. The following will be performed at surveillance visits and are considered standard of care for cancer patients: 1) Medical History Update, 2) Physical examination to include vital signs, 3) Tumor assessments as per standard of care.The patients will be followed for PFS and OS. Progression-free survival (PFS) is defined as the duration of time from study entry to time of progression or death, whichever comes first. Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	From baseline through 36 months