Gemcitabine, Cisplatin, and Radiation Therapy Followed By Surgery or Surgery Alone in Treating Patients With Localized Pancreatic Cancer That Can Be Removed By Surgery

NCT ID: NCT00335543

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 254 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2009-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, 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. Giving chemotherapy together with 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. It is not yet know whether giving chemotherapy together with radiation therapy before surgery is more effective than surgery alone in treating pancreatic cancer.

PURPOSE: This randomized phase II trial is studying how well giving gemcitabine and cisplatin together with radiation therapy before surgery works compared to surgery alone in treating patients with localized pancreatic cancer that can be removed by surgery.

Detailed Description

OBJECTIVES:

Primary

• Determine whether neoadjuvant chemoradiotherapy comprising gemcitabine hydrochloride, cisplatin, and radiotherapy is better than immediate surgery, in terms of median survival, in patients with locally resectable adenocarcinoma of the pancreatic head.

Secondary

• Compare 3-year survival rate in patients treated with these regimens.
• Compare R0 resection rate in these patients.
• Compare the rate of medium and high toxicity events in these patients.
• Compare the rate of complete and incomplete remission of the tumor as measured by radiographic imaging studies.
• Compare the rate of different regression gradings in resected tumor specimens.
• Compare the quality of life of these patients.

OUTLINE: This is a prospective, randomized, controlled, open-label, multicenter study. Patients are stratified according to participating center and staging laparoscopy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes and cisplatin IV over 1 hour on days 1, 8, 22, and 29. Patients also undergo radiotherapy to the tumor and surrounding lymph nodes 5 days a week for 5 weeks followed by 3 more doses of radiotherapy directly to the tumor. Approximately 6 weeks after finishing chemoradiotherapy, patients with no evidence of disease progression undergo surgery to remove the tumor.
• Arm II: Patients undergo surgery to remove the tumor. After surgery, all patients receive adjuvant chemotherapy comprising gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at the end of chemotherapy and before surgery (arm I), and then at 6 weeks, 6 months, 12 months, and 24 months after surgery.

After completion of study treatment, patients are followed every 3 months for 2 years and then at 3 years.

PROJECTED ACCRUAL: A total of 254 patients will be accrued for this study.

Conditions

Pancreatic Cancer

Keywords

adenocarcinoma of the pancreas; stage I pancreatic cancer; stage II pancreatic cancer; stage III pancreatic cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreatic head

• No tumors of the body or tail, as defined by a tumor lying between the left border of the superior mesenteric vein and the left border of the aorta and/or the left border of the aorta and the hilum of the spleen
• Locally resectable disease by CT scan

• Major vessels (e.g., portal vein, confluence of mesenteric and splenic vein, superior mesenteric artery, celiac trunk, splenic artery, hepatic artery, or superior mesenteric vein) maximally enclosed ≤ 180° by the tumor
• No infiltration of extrapancreatic organs except the duodenum
• No carcinoma of the ampulla of Vater
• No metastasis
• No peritoneal carcinoma

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Creatinine clearance > 70 mL/min
• Creatinine < 1.5 mg/dL
• Platelet count > 100,000/mm³
• No liver cirrhosis
• Not pregnant
• No New York Heart Association class III or IV heart disease
• No respiratory insufficiency
• No grade III or IV cardiac arrhythmias
• No pathology on EKG
• No other severe cardiopulmonary disease
• No HIV infection
• No other disease that renders the patient unsuitable for one treatment option
• No other malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other cancer for which the patient was treated with surgery only and has been in complete remission for ≥ 10 years

PRIOR CONCURRENT THERAPY:

• At least 3 months since prior participation in another clinical trial
• No prior or other concurrent treatment for carcinoma of the pancreas

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Interdisziplinare Arbeitsgruppe Gastrointestinaler Tumore der Deutschen Krebsgesellschaft

OTHER

Sponsor Role: lead

Principal Investigators

W. Hohenberger, MD

Role: STUDY_CHAIR

Universitaet Erlangen

Locations

Innsbruck Universitaetsklinik

Innsbruck, , Austria

Allgemeines Krankenhaus - Universitatskliniken

Vienna, , Austria

Robert Roessle Comprehensive Cancer Center - Charite Campus Buch

Berlin, , Germany

Knappschaft Krankenhaus

Bochum, , Germany

DIAKO Ev. Diakonie Krankenhaus gGmbH

Bremen, , Germany

Krankenhaus Dresden - Friedrichstadt

Dresden, , Germany

Universitaet Erlangen

Erlangen, , Germany

Arbeitsgruppe Lebermetastasen und Tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie

Frankfurt, , Germany

Klinik am Eichert

Göppingen, , Germany

Chirurgische Universitaetsklinik

Heidelberg, , Germany

Universitaet Leipzig

Leipzig, , Germany

Staedtisches Klinikum Magdeburg

Magdeburg, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Klinikum Nuernberg - Klinikum Nord

Nuremberg, , Germany

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Kantonsspital - St. Gallen

Sankt Gallen, , Switzerland

Countries

Austria; Germany; Switzerland

References

Golcher H, Brunner T, Grabenbauer G, Merkel S, Papadopoulos T, Hohenberger W, Meyer T. Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. Eur J Surg Oncol. 2008 Jul;34(7):756-64. doi: 10.1016/j.ejso.2007.11.012. Epub 2008 Jan 10.

Reference Type: RESULT

PMID: 18191528 (View on PubMed)

Golcher H, Brunner TB, Witzigmann H, Marti L, Bechstein WO, Bruns C, Jungnickel H, Schreiber S, Grabenbauer GG, Meyer T, Merkel S, Fietkau R, Hohenberger W. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase II trial. Strahlenther Onkol. 2015 Jan;191(1):7-16. doi: 10.1007/s00066-014-0737-7. Epub 2014 Sep 25.

Reference Type: DERIVED

PMID: 25252602 (View on PubMed)

Other Identifiers

CDR0000472206

Identifier Type: REGISTRY

Identifier Source: secondary_id

EU-20609

Identifier Type: -

Identifier Source: secondary_id

ISRCTN78805636

Identifier Type: -

Identifier Source: secondary_id

IAGTDK-70-3046-Ho2

Identifier Type: -

Identifier Source: org_study_id