A Phase II Study Induction Chemotherapy, Neoadjuvant Chemoradiotherapy, Surgical Resection and Adjuvant Chemotherapy for Patients With Locally Advanced, Resectable Pancreatic Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- gemcitabine hydrochloride
- Conditions
- Adenocarcinoma of the Pancreas
- Sponsor
- University of Washington
- Enrollment
- 35
- Locations
- 1
- Primary Endpoint
- Median Overall Survival of Patients With Adenocarcinoma of the Pancreas
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase II trial studies how well giving combination chemotherapy together with intensity-modulated radiation therapy (IMRT) and surgery works in treating patients with localized pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, docetaxel, capecitabine, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving more than one drug (combination chemotherapy) together with intensity-modulated radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the median overall survival of patients with adenocarcinoma of the pancreas treated with induction chemotherapy, neoadjuvant chemoradiotherapy, surgical resection and adjuvant chemotherapy. SECONDARY OBJECTIVES: I. To determine the percent of patients surviving at annual intervals through five years. II. To determine the median recurrence free survival following pancreaticoduodenectomy. III. To determine the clinical response rate to neoadjuvant chemotherapy and chemoradiotherapy. IV. To determine the pathologic response rate to neoadjuvant chemotherapy and chemoradiotherapy. V. To determine the cancer antigen (CA) 19-9 tumor marker response rate to neoadjuvant chemotherapy and chemoradiotherapy. VI. To determine the surgical completion rate and complication rate following neoadjuvant chemotherapy and chemoradiotherapy. VII. To determine the frequency and severity of toxicities associated with this treatment regimen. OUTLINE: INDUCTION CHEMOTHERAPY: Patients receive gemcitabine hydrochloride intravenously (IV) over 75 minutes and docetaxel IV over 30 or 60 minutes on days 4 and 11. Patients also receive capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. NEOADJUVANT CHEMORADIOTHERAPY: Beginning no more than 14 days after completion of induction chemotherapy, patients receive capecitabine PO BID on days 1-14 and oxaliplatin IV over 2 hours on days 1 and 8. Patients also undergo IMRT once daily on days 1-5 and 8-13. SURGICAL RESECTION: Approximately 2-6 weeks after completion of neoadjuvant chemoradiotherapy, patients undergo pancreaticoduodenectomy. ADJUVANT CHEMOTHERAPY: Beginning 4-10 weeks after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.
Investigators
Andrew Coveler
Principal Investigator
University of Washington
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed diagnosis of localized, resectable or borderline resectable, pancreatic adenocarcinoma T1-T3, N0-N1, M0; stage is determined by helical multi-phase computed tomography (CT) and/or endoscopic ultrasound according to published guidelines; resectability is determined by the treating surgeon and published guidelines (National Comprehensive Cancer Network)
- •Resectable Disease- Head/Body/Tail of pancreas:
- •No distant metastases
- •Clear fat plane around celiac and superior mesenteric arteries (SMA)
- •Patent superior mesenteric vein (SMV) and portal vein (PV)
- •Borderline Resectable Disease -Head/Body of pancreas:
- •Tumor abutment on SMA
- •SMV/portal vein impingement or occlusion if involving only a short segment, with open vein both proximally and distally (if proximal vein is occluded up to the portal vein branches then disease is unresectable)
- •Colon or mesocolon invasion
- •Gastroduodenal artery (GDA) encasement up to origin at hepatic artery
Exclusion Criteria
- •Patients may not be receiving any other investigational agents
- •Histology other than adenocarcinoma
- •Patients with permanently unresectable pancreatic adenocarcinoma as determined by the treating physician and published guidelines (National Comprehensive Cancer Network)
- •Unresectable disease
- •Head of pancreas:
- •Distant metastases (includes celiac and/or para-aortic)
- •SMA, celiac encasement
- •SMV/portal occlusion
- •Aortic, inferior vena cava (IVC) invasion or encasement
- •Invasion of SMV below transverse mesocolon
Arms & Interventions
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: gemcitabine hydrochloride
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: docetaxel
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: capecitabine
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: intensity-modulated radiation therapy
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: oxaliplatin
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: pancreatic surgical procedure
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: therapeutic conventional surgery
Treatment (chemotherapy, radiation, pancreaticoduodenectomy)
See Detailed Description
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Median Overall Survival of Patients With Adenocarcinoma of the Pancreas
Time Frame: 5 years
Time at which Kaplan-Meier estimate of overall survival drops below 50%
Secondary Outcomes
- Percent of Patients Surviving at 5 Years(Up to 5 years)
- Median Recurrence Free Survival Following Pancreaticoduodenectomy(From the date of pancreaticoduodenectomy to date of first observation of radiographic recurrence or death due to any cause, assessed up to 7 years)
- Clinical Response Rate to Neoadjuvant Chemotherapy and Chemoradiotherapy(Up to 7 years)
- Pathologic Response Rate (Complete, Near-complete, Partial) to Neoadjuvant Chemotherapy and Chemoradiotherapy(Up to 7 years)
- CA 19-9 Tumor Marker Response Rate to Neoadjuvant Chemotherapy and Chemoradiotherapy(Up to 26 weeks after surgery)
- Surgical Completion Rate and Complication Rate(Up to 6 weeks following the completion of chemoradiotherapy)
- Frequency and Severity of Toxicities Associated With This Treatment Regimen as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0(Up to 26 weeks after surgery (the end of adjuvant chemotherapy))
- Percent of Patients Surviving at Annual Intervals(5 years)