This phase III trial compares the effect of adding panitumumab to standard chemotherapy (with nanoliposomal Irinotecan, leucovorin, and 5-fluorouracil \[5-FU\] or irinotecan, leucovorin, and 5-FU or nab-paclitaxel and gemcitabine) versus standard chemotherapy alone in treating patients with KRAS wild type (WT) pancreatic ductal adenocarcinoma that cannot be removed by sugery (unresectable) or that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Panitumumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Chemotherapy drugs, such as nanoliposomal irinotecan, leucovorin, 5-FU, irinotecan, nab-paclitaxel and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding panitumumab to standard chemotherapy may be effective in treating patients with unresectable, locally advanced, or metastatic KRAS WT pancreatic ductal adenocarcinoma.
Participants must have a histologically or cytologically confirmed diagnosis of ductal adenocarcinoma of the pancreas
Participants must have previously documented KRAS wild type (i.e. absence of any KRAS mutation) and BRAF V600E wild type (i.e. absence of a BRAF V600E mutation) status determined by tumor tissue-based NGS assay. The testing must be done within a laboratory with Clinical Laboratory Improvement Act (CLIA), International Organization for Standardization (ISO)/International Electrotechnical Commission (IEC), College of American Pathologists (CAP), or similar certification status
NOTE: Blood-based next generation sequencing (NGS) assays, such as circulating tumor deoxyribonucleic acid (DNA) (ctDNA) or liquid biopsies, will not be accepted for meeting eligibility criteria
Participants must have documented unresectable and/or metastatic disease on CT or magnetic resonance imaging (MRI) imaging completed prior to randomization. Imaging must have been completed within 28 days prior to randomization for participants with measurable disease. CT scans or MRIs used to assess non-measurable disease must have been completed within 42 days prior to randomization. All disease must be assessed and documented on the Baseline Tumor Assessment Form (In calculating days of tests and measurements, the day a test or measurement is done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 4 weeks later would be considered Day 28. This allows for efficient participant scheduling without exceeding the guidelines. If Day 14 or 28 falls on a weekend or holiday, the limit may be extended to the next working day)
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
Fluorouracil
DrugGiven IV
Gemcitabine
DrugGiven IV
Irinotecan
DrugGiven IV
Irinotecan Sucrosofate
DrugGiven IV
Leucovorin
DrugGiven IV
Nab-paclitaxel
DrugGiven IV
Panitumumab
Biological/VaccineGiven IV
Questionnaire Administration
Other interventionAncillary studies
Overall survival (OS)
Analysis of OS will be conducted in all eligible participants according to the intent-to-treat principle using a 1-sided stratified log rank test.
Objective response rate (ORR)
Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be compared across treatment arms via Fisher's exact test.
Disease control rate
Will be compared across treatment arms via Fisher's exact test.
Duration of response (DoR)
The distributions of DoR will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.
Progression free survival (PFS)
The distributions of PFS will be estimated using the method of Kaplan-Meier and compared using the stratified log rank test.
Health-related quality of life (QOL)
Measured by the Functional Assessment of Cancer Therapy - General (FACT-G) total score. Analysis will be conducted using multiple linear regression analysis, adjusting for the clinical study-specified stratification factors (which are also anticipated to influence QOL endpoints), and the baseline score as covariates.
Impact of treatment toxicity
Measured by the Functional Assessment of Chronic Illness Therapy Item GP5 (FACIT Item GP5). Analysis will be conducted using multiple linear regression analysis, adjusting for the clinical study-specified stratification factors, and the baseline score as covariates.
Changes in health related QOL
Will be assessed using FACT-G total score. Linear regression models will be used for longitudinal modeling, with robust errors estimated via generalized estimating equations to adjust for correlation between repeated outcome measures. Covariates for longitudinal modeling will include intervention assignment, the assessment timepoint, the baseline score, and the stratification factors. The potential for differential dropout by arm will be mitigated by reminder notifications to site investigators to encourage proper assessment and submission of forms at every required time point for all participants. Cohort plots will be prepared to examine the extent to which missing data are informative (i.e., scores are higher (worse) for participants just before their data are missing for the subsequent assessment). If there is evidence of non-random dropout, pattern-mixture models will be utilized as a sensitivity analysis.
Change in impact of treatment toxicity
Will be assessed using FACIT Item GP5. Linear regression models will be used for longitudinal modeling, with robust errors estimated via generalized estimating equations to adjust for correlation between repeated outcome measures. Covariates for longitudinal modeling will include intervention assignment, the assessment timepoint, the baseline score, and the stratification factors. The potential for differential dropout by arm will be mitigated by reminder notifications to site investigators to encourage proper assessment and submission of forms at every required time point for all participants. Cohort plots will be prepared to examine the extent to which missing data are informative (i.e., scores are higher (worse) for participants just before their data are missing for the subsequent assessment). If there is evidence of non-random dropout, pattern-mixture models will be utilized as a sensitivity analysis.
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SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator
