Clinical trial NCT06958328: Testing Higher Dose Radiation Therapy for Locally Advanced Pancreatic Cancer
Official title: Official Title A Phase III Randomized Trial of Dose Escalated Radiation in Locally Advanced Pancreas Cancer (LAPC) Patients (LAP100)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Pancreas Cancer
Lead sponsor: NRG Oncology
Sponsor class: OTHER
First posted: 2025-05-06
Enrollment: 356
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: No Data
Primary purpose: TREATMENT

Brief 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 fractions and receive 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.

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 fluoropyrimidine). 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.

After completion of study treatment, patients are followed up every 3 months for 2 years then annually for 3 years.

Eligibility criteria: Inclusion Criteria:

* • At time of enrollment, the patient must have received 4-6 months of active chemotherapy with FOLFIRINOX (8-12 cycles) or NALIRIFOX (8-12 cycles) or gemcitabine/nab-paclitaxel (4-6 cycles) (1 regimen, no sequential chemotherapy). "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, or CT chest/CT pelvis/MRI abdomen performed prior to enrollment
  * Age ≥ 18 years
  * Performance status Eastern Cooperative Oncology Group (ECOG) 0-2
  * Baseline CA19-9 with a normal bilirubin level (defined as ≤ 1.2 mg/dl)
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
  * 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 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

Exclusion Criteria:

-

Primary outcomes:
measure: Overall survival (OS)
timeFrame: assessed up to 3 years
Secondary outcomes:
measure: Local progression (LP)
timeFrame: From randomization to date of failure, date of death (competing event), or last known follow-up date, assessed up to 5 years
measure: Progression-free survival (PFS)
timeFrame: From the date of randomization to the date of first PFS failure or last follow-up for patients without a reported PFS event, assessed up to 5 years
measure: Chemotherapy-free interval (CFI)
timeFrame: From the date of last dose of initial chemotherapy to the date of first dose of second line chemotherapy for progression, assessed up to 5 years
measure: Long-term radiation-related ≥ grade 3 adverse events
timeFrame: Up to 1 year
measure: Incidence of ≥ grade 3 adverse events
timeFrame: Up to 90 days after randomization
Other outcomes:
measure: Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) total score at 6 months
timeFrame: At 6 months
measure: FACT-Hep score nadir
timeFrame: From baseline to 24 months from randomization
measure: FACT-Hep total score over time
timeFrame: From baseline to 24 months from randomization
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