The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.
OBJECTIVES: Primary * Phase I: To determine the feasibility and tolerability of radiation therapy for pancreatic cancer delivered with high dose external beam radiation in a one week accelerated schedule with concurrent capecitabine * Phase II: To demonstrate a grade 3 or greater (any) toxicity rate of less than 20% Secondary * To determine local control and recurrence patterns of pancreatic cancer relative to a standard regimen of 50.4 Gy as seen in historical controls * To determine the pathologic response rate * To determine the progression-free survival * To determine the surgical morbidity * To determine 30-day post-operative mortality after pancreatic resection
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Brigham and Women's Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]
Neoadjuvant short-course photon radiation therapy MTD in combination with capecitabine 825 mg/m2 orally BID for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If none of 3 initial patients or only 1 of 6 patients have a DLT on dose level 3 then 6 additional patients are treated at this dose. If during this expansion, the rate of DLT exceeds 30% then the next lower dose level is declared the MTD. If no DLTs are observed, the MTD is not reached.
Time frame: within 3 weeks of the start of chemoradiation therapy
Dose Limiting Toxicity (DLT) [Phase I]
DLT occurring within 3 weeks of the start of chemoradiation therapy was defined as: Grade 3 non-hematologic or hematologic toxicity requiring interruption of \>7 days (d) of chemo or \>3d chemoradiation; Grade 4 non-hematologic; Grade 4 neutropenia or thrombocytopenia; Treatment-related death; Delays in surgery \>3 weeks due to treatment-related toxicity. A 30% increase in any surgical complication rate beyond those previously established rates (readmission rate: 16%; pancreatic fistula/intra-abdominal abscess/infection rate: 27%, major intra-abdominal bleeding requiring return to OR: 1.6%, delayed gastric emptying: 4.4%, and superficial wound infection rate: 8%) was also considered a DLT.
Time frame: within 3 weeks of the start of chemoradiation therapy
Grade 3-5 Toxicity Rate [Phase II]
All Grade 3-5 events based on CTCAEv3 related to the accelerated dose (attribution possible, probable, definite) as reported on case report forms.
Time frame: within 3 weeks of the start of chemoradiation therapy
Local Recurrence Rate [Phase II]
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Local recurrence rate is defined as the proportion of patients with evidence of tumor recurrence within the radiation field based on RECIST criteria. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Pathologic Response Rate [Phase II]
Pathologic response rate is the proportion of patients with the pathologic specimen absent any viable tumor cell. Pathological review of the pancreaticoduodenectomy specimen will be performed according to the AJCC Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist.
Time frame: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Progression-Free Survival (PFS) [Phase II]
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Patients alive whose disease had not progressed are censored at date of last disease evaluation
Time frame: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
Surgical Morbidity Rate [Phase II]
The proportion of patients experienced any grade 3-4 adverse event based on CTCAEv3 related to the surgery (attribution possible, probable, definite) as reported on case report forms.
Time frame: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Surgical Mortality Rate [Phase II]
The proportion of patients with a death related to the surgery (CTCAEv3 attribution possible, probable, definite).
Time frame: Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy