Dysautonomia International

Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer

Purpose

This phase III trial compares the effect of dose-escalated radiation therapy to usual care in patients with locally advanced unresectable pancreatic ductal adenocarcinoma who have received an initial 4-6 months of chemotherapy. Usual care options include additional chemotherapy, observation, or standard lower-dose radiation therapy. These treatments may delay tumor growth but have not been shown to improve survival. Radiation therapy uses high energy X-rays to kill cancer cells and shrink tumors. Dose-escalated radiation therapy involves the precise delivery of higher doses to the tumor, often over a shorter period of time. This trial assesses whether using dose-escalated radiation therapy can prolong survival.

Conditions

Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma
Stage II Pancreatic Cancer AJCC v8
Stage III Pancreatic Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

- At time of enrollment, the patient must have received 4-6 months of active
chemotherapy with FOLFIRINOX or NALIRIFOX or gemcitabine/nab-paclitaxel. Patients
are permitted to receive more than 1 type of chemotherapy for toxicity reasons, but
not for disease progression. "Active chemotherapy" refers to time on chemotherapy
not counting treatment breaks (i.e. if a patient had 1 month of chemotherapy
followed by 1 month break, this would count as 1 month chemotherapy). Study
registration must occur within 45 days of last day of chemotherapy cycle

- BASELINE PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:

- Pathologically (histologically or cytologically) proven diagnosis of pancreatic
ductal adenocarcinoma

- Locally advanced unresectable disease (as defined per the National Comprehensive
Cancer Network [NCCN] guidelines and institutional tumor board review)

- Patients must have baseline pre-chemotherapy scans for staging. Options include: CT
chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, CT chest/CT pelvis/MRI abdomen,
or PET/CT performed prior to enrollment

- Age ≥ 18 years

- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2

- Required initial laboratory values:

All laboratory values must be obtained any time prior to initiation of chemotherapy up to
30 days post initiation of chemotherapy

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper
limit of normal (ULN)

- BASELINE CA19-9 AND BILIRUBIN REQUIREMENTS: The purpose is to obtain a baseline
CA19-9 in the setting of a normal (or close to normal) bilirubin, since serologic
response by serial CA19-9 measurements is part of post-chemotherapy eligibility
criteria

- If baseline CA19-9 > 37 U/mL the concurrent bilirubin must be ≤ 1.5 x ULN.
(Note: if the bilirubin is not ≤ 1.5 x ULN both the CA19-9 and concurrent
bilirubin can be repeated until bilirubin is ≤ 1.5 x ULN, as long as done
within specified timeframe [up to 30 days post chemotherapy initiation])

- If baseline CA19-9 U/mL ≤ 37, there are no restrictions on the required
concurrent bilirubin level, and this can be the accepted baseline value

- Prior radiation treatment

- Has the patient had prior radiotherapy to the region of the study cancer that would
result in overlap of radiation therapy fields

- Prior non-overlapping radiation (e.g., breast, head and neck, extremity) is
permitted

- If uncertain about prior overlap, please contact the study principal investigator,
Dr. Nina Sanford

- POST PRE-ENTRY CHEMOTHERAPY REQUIREMENTS:

- If baseline CA19-9 is elevated (defined as > 37 u/mL) the post-pre-entry
chemotherapy CA19-9 must be less than 37 u/mL or a 50% decline from
pre-chemotherapy level with absolute value less than 100u/mL

- If baseline CA19-9 is not elevated (defined as ≤ 37 u/mL) the post-pre-entry
chemotherapy CA19-9 must remain ≤ 37 u/mL

- No active duodenal or gastric ulcers

- No direct tumor invasion of the bowel or stomach

- Restaging scans showing at least stable disease (no progression). Options for
scans include: CT chest/abdomen/pelvis, CT chest/MRI abdomen/pelvis, or CT
chest/CT pelvis/MRI abdomen, or PET/CT performed prior to enrollment, with
restaging CT showing at least stable disease

- Not pregnant and not nursing

- No cardiac condition that was the primary reason for hospitalization in the
last 6 months

- New York Heart Association Functional Classification II or better (NYHA
Functional Classification III/IV are not eligible) (Note: Patients with known
history or current symptoms of cardiac disease, or history of treatment with
cardiotoxic agents, should have a clinical risk assessment of cardiac function
using the New York Heart Association Functional Classification.)

- HIV-infected patients on effective anti-retroviral therapy with undetectable
viral load within 6 months are eligible for this trial

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator Arm I (Options 1, 2, or 3)	See Detailed Description.	Procedure: Biopsy Procedure Undergo tumor tissue biopsy Other names: Biopsy BIOPSY_TYPE Bx Procedure: Biospecimen Collection Undergo blood sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Capecitabine Given capecitabine Other names: Ro 09-1978/000 Xeloda Procedure: Computed Tomography Undergo CT or PET/CT Other names: CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Drug: Fluorouracil Given fluorouracil Other names: 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Drug: Gemcitabine Given gemcitabine Other names: dFdC dFdCyd Difluorodeoxycytidine Drug: Irinotecan Hydrochloride Given irinotecan hydrochloride Other names: Campto Camptosar Camptothecin 11 Camptothecin-11 CPT 11 CPT-11 CPT11 Irinomedac Irinotecan Hydrochloride Trihydrate Irinotecan Monohydrochloride Trihydrate U 101440E U-101440E U101440E Drug: Irinotecan Sucrosofate Given liposomal irinotecan Other names: inotecan Hydrochloride as Sucrosulfate Salt Form Liposomal Formulation Irinotecan Liposome Irinotecan Sucrosofate Liposome Irinotecan Sucrosofate-containing Pegylated Liposomal Formulation MM 398 MM-398 MM398 nal-IRI Nanoliposomal Irinotecan Nanoliposomal Irinotecan as Sucrosofate Nanoparticle Liposome Formulation of Irinotecan Onivyde PEP 02 PEP-02 PEP02 Drug: Leucovorin Calcium Given leucovorin calcium Other names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Drug: Nab-paclitaxel Given nab-paclitaxel Other names: ABI 007 ABI-007 ABI007 Abraxane Albumin-bound Paclitaxel Albumin-Stabilized Nanoparticle Paclitaxel Nanoparticle Albumin-bound Paclitaxel Nanoparticle Paclitaxel Naveruclif Paclitaxel Albumin paclitaxel albumin-stabilized nanoparticle formulation Paclitaxel Nanoparticle Albumin-bound Paclitaxel Protein-Bound Protein-bound Paclitaxel Other: Observation Activity Undergo observation Other names: Observation Drug: Oxaliplatin Given oxaliplatin Other names: 1-OHP Ai Heng Aiheng Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine Elplat JM 83 JM-83 JM83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 RP54780 SR 96669 SR-96669 SR96669 Procedure: Positron Emission Tomography Undergo PET/CT Other names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Other: Questionnaire Administration Ancillary studies Radiation: Radiation Therapy Undergo standard radiation therapy Other names: Cancer Radiotherapy Energy Type ENERGY_TYPE Irradiate Irradiated Irradiation Radiation Radiation Therapy, NOS Radiotherapeutics Radiotherapy RT Therapy, Radiation
Experimental Arm II (dose-escalated RT)	Patients undergo dose-escalated RT daily, every other day, or twice weekly for 5 fractions or daily for 25 fractions (with or without concurrent fluorouracil or capecitabine for 25 fractions only). The 5-fraction regimen is preferred when feasible. After completing dose-escalated RT, patients who received less than 6 months of chemotherapy at study entry are encouraged to receive the remaining chemotherapy to total 6 months of chemotherapy. Patients may continue chemotherapy treatment beyond 6 months at physician's discretion. Additionally, patients undergo blood sample collection, CT, MRI and tumor tissue biopsy throughout the study. Patients may optionally undergo PET/CT prior to treatment.	Procedure: Biopsy Procedure Undergo tumor tissue biopsy Other names: Biopsy BIOPSY_TYPE Bx Procedure: Biospecimen Collection Undergo blood sample collection Other names: Biological Sample Collection Biospecimen Collected Specimen Collection Drug: Capecitabine Given capecitabine Other names: Ro 09-1978/000 Xeloda Procedure: Computed Tomography Undergo CT or PET/CT Other names: CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Radiation: Dose-escalated Radiation Therapy Undergo dose-escalated radiation using intensity-modulated radiation therapy treatment planning Other names: Dose-escalated RT Drug: Fluorouracil Given fluorouracil Other names: 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-Fu 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Procedure: Magnetic Resonance Imaging Undergo MRI Other names: Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Procedure: Positron Emission Tomography Undergo PET/CT Other names: Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Other: Questionnaire Administration Ancillary studies

Recruiting Locations

Banner MD Anderson Cancer Center
Gilbert, Arizona 85234

Contact:
Site Public Contact
602-747-9738

Arizona Center for Cancer Care - Gilbert
Gilbert, Arizona 85297

Contact:
Site Public Contact
480-278-8261
penny.labriola@arizonaccc.com

Arizona Center for Cancer Care-Peoria
Peoria, Arizona 85381

Contact:
Site Public Contact
623-773-2873

Arizona Center for Cancer Care - Phoenix
Phoenix, Arizona 85027

Contact:
Site Public Contact
480-278-8261
penny.labriola@arizonaccc.com

Arizona Center for Cancer Care - Scottsdale
Scottsdale, Arizona 85258

Contact:
Site Public Contact
480-278-8261
penny.labriola@arizonaccc.com

Arizona Center for Cancer Care-Surprise
Surprise, Arizona 85374

Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Arizona Center for Cancer Care
Tempe, Arizona 85284

Contact:
Site Public Contact
480-278-8261
penny.labriola@arizonaccc.com

NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro, Arkansas 72401

Contact:
Site Public Contact
870-936-7066
Emily.Carvell@bmhcc.org

AIS Cancer Center at San Joaquin Community Hospital
Bakersfield, California 93301

Contact:
Site Public Contact
661-323-4673

Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California 94704