NCT06958328

Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer

A Phase III Randomized Trial of Dose Escalated Radiation in Locally Advanced Pancreas Cancer (LAPC) Patients (LAP100)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 356 (estimated)
• Sponsor: NRG Oncology · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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.

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

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tumor tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Capecitabine	Given capecitabine
PROCEDURE	Computed Tomography	Undergo CT or PET/CT
RADIATION	Dose-escalated Radiation Therapy	Undergo dose-escalated radiation using intensity-modulated radiation therapy treatment planning
DRUG	Fluorouracil	Given fluorouracil
DRUG	Gemcitabine	Given gemcitabine
DRUG	Irinotecan Hydrochloride	Given irinotecan hydrochloride
DRUG	Irinotecan Sucrosofate	Given liposomal irinotecan
DRUG	Leucovorin Calcium	Given leucovorin calcium
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Nab-paclitaxel	Given nab-paclitaxel
OTHER	Observation Activity	Undergo observation
DRUG	Oxaliplatin	Given oxaliplatin
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
OTHER	Questionnaire Administration	Ancillary studies
RADIATION	Radiation Therapy	Undergo standard radiation therapy

Timeline

• Start date: 2025-08-21
• Primary completion: 2030-10-21
• Completion: 2030-10-21
• First posted: 2025-05-06
• Last updated: 2026-04-08

Locations

279 sites across 1 country: United States