Combination Chemotherapy With or Without Hypofractionated Radiation Therapy Before Surgery in Treating Patients With Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, 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. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy. SECONDARY OBJECTIVES: I. To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens. II. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens. III. To evaluate and estimate the pathologic compete response (pCR) rates in patients receiving each of the two multimodality treatment regimens. IV. To assess the adverse events (AE) profile and safety of each treatment arm. TERTIARY OBJECTIVES: I. To test the effect of the rs2853564 vitamin D receptor (VDR) variant on OS rate and discover novel candidate genes associated with OS and severe toxicity of chemotherapy by using genome-wide genotyping approaches. II. To evaluate risk classification previously developed by Koay et al using normalized area under the enhancement curve (NAUC). III. To access prognostic value of NAUC ratio defined as post-neoadjuvant NAUC divided by pre-neoadjuvant therapy NAUC. IV. To evaluate risk classification previously developed by Koay et al using delta measure. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 8 courses in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 7 courses in the absence of disease progression or unacceptable toxicity. Patients receive either stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT) on days 1-5 of course 8. SURGERY Within 4 to 8 weeks after the last dose of chemotherapy (arm A) or of radiation (arm B), patients considered surgical candidates for resection (after central review) will undergo surgery at the registering institution. ADJUVANT CHEMOTHERAPY Within 4-12 weeks from the date of surgery, patients will receive oxaliplatin IV over 2 hours and leucovorin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46-48 hours on days 1-2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 16 weeks for 2 years, then every 6 months for 5 years.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS) Rate [18 months]. Number, percentage of patients. Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) (n=65): 64.6; Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) (n=55): 47.3.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Residual Tumor (R)0 Resection Rate [24 months]. Number, percentage of patients. Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) (n=65): 49; Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) (n=55): 35.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Event-free Survival [4 years and 7 months]. Median, Months (95% Confidence Interval). Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) (n=65): 15.0 (11.2 to 21.9); Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) (n=55): 10.2 (6.7 to 17.3).

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Pathologic Complete Rate (pCR) Rate [24 months]. Number, percentage of patients. Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) (n=65): 0; Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) (n=55): 11.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE [1 year]. Count Of Participants, Participants. Arm 1 (mFOLFIRINOX + Surgery + FOLFOX) (n=66): 66; Arm 2 (mFOLFIRINOX + Radiation + Surgery + FOLFOXx) (n=55): 55.