Combination Chemotherapy, Intensity-Modulated Radiation Therapy, and Surgery in Treating Patients With Localized Pancreatic Cancer That Can Be Removed By Surgery

Adenocarcinoma of the Pancreas Clinical Trial

Official title:

A Phase II Study Induction Chemotherapy, Neoadjuvant Chemoradiotherapy, Surgical Resection and Adjuvant Chemotherapy for Patients With Locally Advanced, Resectable Pancreatic Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00609336
• Other study ID #: 6511
• Secondary ID: NCI-2010-0055365
• Status: Completed
• Phase: Phase 2
• First received: February 6, 2008
• Last updated: January 6, 2017
• Start date: January 2008
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: December 2016
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Tail of pancreas:

• Adrenal, colon or mesocolon, or kidney invasion

• Preoperative evidence of biopsy-positive peripancreatic lymph node

• No prior therapy for pancreatic cancer

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

• Leucocytes >= 3,000/uL

• Absolute Neutrophil Count >= 1,500/uL

• Platelets >= 100,000/uL

• Total Bilirubin:

• If within normal limits (WNL) to =< 2.0, the subject is eligible

• If > 2.0 - < 6.0, subject is eligible IF they have a biliary stent and total bilirubin is decreasing

• If >= 6.0, subject is not eligible

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal or =< 1.5 X upper limit of normal (ULN) if alkaline phosphatase (Alk Phos) > 2.5 X ULN or if the subject has a biliary stent and the liver function tests (LFTs) are decreasing the subject is eligible

• Creatinine clearance >= 30%

• Negative pregnancy test for women of childbearing potential; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• Ability to swallow and retain oral medication

• Ability to understand and willingness to sign a written informed consent document

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

• Body of pancreas:

• Distant metastases (includes celiac and/or para-aortic); at the discretion of the treating surgeon, body and tail lesions that have positive celiac and/or para-aortic nodes in close vicinity to the primary may be borderline rather than unresectable

• SMA, celiac, hepatic encasement

• SMV/portal extended occlusion

• Aortic invasion

• Tail of pancreas:

• Distant metastases (includes celiac and/or para-aortic)

• SMA, celiac encasement

• Rib, vertebral invasion

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, docetaxel, capecitabine, oxaliplatin or other agents used in the study

• Patients who have received prior chemotherapy or radiotherapy for the diagnosis of pancreatic cancer

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Inability to comply with study and/or follow-up procedures

• Pregnancy or lactation

• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Stage IA Pancreatic Cancer
• Stage IB Pancreatic Cancer
• Stage IIA Pancreatic Cancer
• Stage IIB Pancreatic Cancer

Intervention

Drug:
• gemcitabine hydrochloride
Given IV
• docetaxel
Given IV
• capecitabine
Given PO

Radiation:
• intensity-modulated radiation therapy
Undergo IMRT

Drug:
• oxaliplatin
Given IV

Procedure:
• pancreatic surgical procedure
Undergo pancreaticoduodenectomy
• therapeutic conventional surgery
Undergo therapeutic conventional surgery

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median overall survival of patients with adenocarcinoma of the pancreas	Estimated by the Kaplan Meier method.	From the date of registration to date of death due to any cause, assessed up to 22 months	No
Secondary	Percent of patients surviving		Up to 5 years	No
Secondary	Median recurrence free survival following pancreaticoduodenectomy	The appearance of radiographic findings consistent with recurrent tumor at the local resection site or at a distant location is considered a radiographic recurrence.	From the date of pancreaticoduodenectomy to date of first observation of radiographic recurrence or death due to any cause, assessed up to 7 years	No
Secondary	Clinical response rate to neoadjuvant chemotherapy and chemoradiotherapy	Assessed using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.	Up to 7 years	No
Secondary	Pathologic response rate to neoadjuvant chemotherapy and chemoradiotherapy	The resected pancreaticoduodenectomy specimen and accompanying lymph nodes will be staged according to American Joint Committee on Cancer 6th Edition incorporating the prefix y to indicate a specimen status-post neoadjuvant treatment (ypTNM).	Up to 7 years	No
Secondary	CA 19-9 tumor marker response rate to neoadjuvant chemotherapy and chemoradiotherapy	Biochemical response is a decrease of >= 50% of CA 19-9 serum tumor marker in patients with elevated CA 19-9 at baseline.	Up to 26 weeks after surgery	No
Secondary	Surgical completion rate and complication rate		Up to 6 weeks following the completion of chemoradiotherapy	No
Secondary	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)	Yes