Folfirinox or Gemcitabine-Nab Paclitaxel Followed by Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

NCT03600623 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: IRB160830003 (UAB 1632)
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study will implement a new treatment regimen for patients with advanced and inoperable pancreatic cancer using chemotherapy combinations of Folfirinox or gemcitabine-nab paclitaxel (abraxane) followed by a short course of high dose radiation called Stereotactic Body Radiation Therapy (SBRT). While the chemotherapy is standard of care, the strategy of adding SBRT has not been investigated. An increase in the percentage of patients who can proceed to have surgery to remove their disease is anticipated with this approach.

Conditions

Locally Advanced Pancreatic Cancer; Borderline Pancreatic Inoperable Cancer; Pancreatic Cancer

Keywords

advanced pancreatic cancer; inoperable pancreatic cancer; Folfirinox; Gemcitabine-Abraxane; Gemcitabine-nab-Paclitaxel; Stereotactic Body Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as a measure of safety and tolerability

  Initial dose of drug until 4 weeks following completion of therapy which may or may not include SBRT and follow-up. Adverse event reporting will be graded following the National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

  Baseline up to two years

Secondary Outcomes (4)

• Progression-free survival

  Baseline up to two years

• Overall survival

  Baseline to two years

• Rate of preoperative chemotherapy + radiotherapy completion

  Baseline to two years

• Proportion of participants undergoing surgery after preoperative chemoradiation therapy

  Baseline to two years

Study Arms (2)

Folfirinox + SBRT

EXPERIMENTAL

Folfirinox comprises the following: Fluorouracil 2,400 mg/m2 intravenously over 48 hours Days 1-3 and 15-17 every 4 weeks; Folinic acid 400 mg intravenously on Days 1 and 15 every 4 weeks; Oxaliplatin 85 mg/m2 intravenously on Days 1 and 15 every 4 weeks; and Irinotecan 180 mg/m2 intravenously on Days 1 and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits and will last over a period of 5 days.

Drug: Folfirinox

Gemcitabine-nab Paclitaxel + SBRT

EXPERIMENTAL

Gemcitabine-nab Paclitaxel comprises the following: Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 every 4 weeks; nab Paclitaxel 125 mg/m2 on Days 1, 8, and 15 every 4 weeks. Radiation will begin at the completion of cycle 2 if chemotherapy toxicity permits and will last over a period of 5 days.

Drug: Gemcitabine nab-Paclitaxel

Interventions

Folfirinox DRUG

SBRT will follow Folfirinox at the completion of Cycle 2 (if eligible).

Also known as: Folfirinox = Fluorouracil + Folinic Acid + Oxaliplatin + Irinotecan

Folfirinox + SBRT

Gemcitabine nab-Paclitaxel DRUG

SBRT will follow Gemcitabine nab-Paclitaxel at the completion of Cycle 2 (if eligible).

Also known as: Paclitaxel = Abraxane

Gemcitabine-nab Paclitaxel + SBRT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (βhCG) documented up to 72 hrs 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 ≥100,000/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)

You may not qualify if:

• 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 surgical procedure within 4 weeks prior to enrollment.
• Patient who has a history of allergy or hypersensitivity to any of the study drugs.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Leucovorin; Oxaliplatin; Irinotecan; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Ravi K Paluri, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Patients will be assigned to one of two treatment arms: Arm 1 is Folfirinox (5FU/Leucovorin/Irinotecan/Oxaliplatin) and Arm 2 is Gemcitabine-nab-Paclitaxel (Abraxane). Either arm will be followed with SBRT for eligible patients.

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: September 25, 2017
• Primary Completion: July 30, 2020
• Study Completion: July 31, 2020
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)