Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer

ID#: NCT06958328

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 3

Recruitment Status: Recruiting

Start Date: August 21, 2025

End Date: October 21, 2030

Summary: 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.
Eligibility:

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