UT Health San Antonio

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

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate whether dose-escalated radiation therapy (RT) improves 3-year overall survival (OS) compared to standard treatments without dose-escalated RT, in locally advanced pancreatic cancer patients without radiographic progression and with biochemical response after an initial interval of chemotherapy. SECONDARY OBJECTIVES: I. To evaluate and compare local progression between the two treatment arms. II. To evaluate and compare progression-free survival (PFS) between the two treatment arms. III. To evaluate and compare chemotherapy-free interval between the two treatment arms. IV. To evaluate and compare toxicity within and between the two treatment arms. HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) OBJECTIVES: I. Primary: To compare Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) Total Score at 6 months between the two treatment arms. II. Secondary: To compare nadir of HRQoL scores over course of study participation between the two treatment arms. III. Secondary: To evaluate HRQoL scores over time between the two treatment arms. EXPLORATORY OBJECTIVE: I. Biospecimen collection for future correlative analyses. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (STANDARD OF CARE): Patients are assigned to 1 of 3 treatment options per physician's decision. OPTION 1: Patients continue to receive fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX or modified FOLFIRINOX [mFOLFIRINOX]) or fluorouracil, liposomal irinotecan, leucovorin calcium, and oxaliplatin (NALIRIFOX) or gemcitabine/nab-paclitaxel per standard of care for a total of 6 months of treatment. Patients may continue treatment beyond 6 months at physician's discretion. OPTION 2: Patients undergo standard dose radiation therapy once daily for 28 or 30 fractions and receive concurrent fluorouracil or capecitabine per standard of care during radiation therapy. After completing concurrent chemoradiation, 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. OPTION 3: Patients undergo observation per standard of care. (It is recommended [but not required] that this option only be for patients that have already completed total 6 months chemotherapy pre-randomization.) Additionally, patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) and tumor tissue biopsy throughout the study. Patients may optionally undergo positron emission tomography (PET)/CT prior to treatment. ARM II (DOSE-ESCALATED RADIATION THERAPY): 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. Patients are followed every 3 months from study entry for 2 years then annually for 3 years.