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 (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
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. |
|
|
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. |
|
Recruiting Locations
Kansas City 4273837, Kansas 4273857 66160
Westwood 4281639, Kansas 4273857 66205
Kansas City 4393217, Missouri 4398678 64154
Olathe 4276614, Kansas 4273857 66061
Overland Park 4276873, Kansas 4273857 66210
Lee's Summit 4394870, Missouri 4398678 64064
Topeka 4280539, Kansas 4273857 66606
Site Public Contact
785-295-8000
More Details
- Status
- Recruiting
- Sponsor
- NRG Oncology
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. 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 are followed every 3 months from study entry for 2 years then annually for 3 years.