Clinical trial NCT00058201: Two Chemotherapy Regimens Compared With Observation in Treating Patients With Completely Resected Pancreatic Cancer
Official title: European Study Group For Pancreatic Cancer - Trial 3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: acinar cell adenocarcinoma of the pancreas
duct cell adenocarcinoma of the pancreas
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: NCIC Clinical Trials Group
name: Australasian Gastro-Intestinal Trials Group
First posted: 2003-04-09
Enrollment: 1030
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which chemotherapy regimen is more effective, or whether chemotherapy is more effective than observation, in treating pancreatic cancer after surgery.

PURPOSE: Phase III trial to compare the effectiveness of two chemotherapy regimens with no further therapy in treating patients who have completely resected pancreatic cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the efficacy of adjuvant gemcitabine vs fluorouracil and leucovorin calcium (vs observation only in patients with ampullary or other pancreatic malignancy), in terms of overall survival, in patients with completely resected pancreatic cancer.

Secondary

* Compare the toxicity of these regimens in these patients.
* Compare the quality of life and 5-year survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (ductal adenocarcinoma vs ampullary or other pancreatic malignancy), resection margin status, and participating country. Patients are randomized to 1 of 2 treatment arms. Randomization for patients with ampullary or other pancreatic malignancy includes an observation arm.

* Arm I: Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5.
* Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15.
* Arm III (patients with ampullary or other pancreatic malignancy only): Patients undergo observation.

Treatment in arms I and II repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, 3, 6, and 12 months, and then annually for 5 years.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 1,030 patients with pancreatic adenocarcinoma (515 per arms I and II) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed ductal adenocarcinoma of the pancreas OR
* Histologically confirmed diagnosis of 1 of the following types of cancer:

  * Acinar cell carcinoma or cystadenocarcinoma of the pancreas
  * Cancers of the periampullary region
  * Cancers of the intrapancreatic part of the bile duct
  * Periampullary cancers of uncertain origin
* Complete macroscopic resection (R0 or R1 resection)

  * Histological examination of all resection margins required
* No stage IVB disease
* No evidence of malignant ascites
* No liver or peritoneal metastases
* No evidence of spread to other distant abdominal or extra-abdominal organs
* No pancreatic lymphoma

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* More than 3 months

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Not pregnant
* Able to participate in long-term follow-up
* No other prior or concurrent malignancy except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
* No serious medical or psychological condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No neoadjuvant chemotherapy
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* See Disease Characteristics
* Recovered from prior resection

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Toxicity as measured by NCI CTC v2.0
measure: Quality of life as measured by EORTC QLQ C-30 and ESPAC-QLQ at 3, 6, and 12 months, and then annually for 5 years
measure: Survival rate at 2 and 5 years
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: Institute of Oncology at Prince of Wales Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Victoria
country: Canada
facility: British Columbia Cancer Agency - Vancouver Island Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Cancer Research Institute at Queen's University
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Edmond Odette Cancer Centre at Sunnybrook
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre - Toronto
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Preha 4
country: Czech Republic
facility: Institute for Clinical and Experimental Medicine
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Paris
country: France
facility: Hopital Tenon
city: Heidelberg
country: Germany
facility: Universitaets-Kinderklinik Heidelberg
city: Athens
country: Greece
facility: Agia Olga Hospital
city: Gydr
country: Hungary
facility: Petz Aladar County Hospital
city: Verona
country: Italy
facility: Policlinico Borgo Roma
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
Study officials:
affiliation: Royal Liverpool University Hospital
name: John P. Neoptolemos, MD
role: STUDY_CHAIR
affiliation: Princess Margaret Hospital, Canada
name: Malcolm J. Moore, MD
role: STUDY_CHAIR
affiliation: Flinders Medical Centre
name: R. Padbury
affiliation: Institute of Oncology at Prince of Wales Hospital
name: David Goldstein, MD
References:
citation: Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC, Carter R, Tebbutt NC, Dervenis C, Smith D, Glimelius B, Charnley RM, Lacaine F, Scarfe AG, Middleton MR, Anthoney A, Ghaneh P, Halloran CM, Lerch MM, Olah A, Rawcliffe CL, Verbeke CS, Campbell F, Buchler MW; European Study Group for Pancreatic Cancer. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012 Jul 11;308(2):147-56. doi: 10.1001/jama.2012.7352.
citation: Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, Padbury R, Moore MJ, Gallinger S, Mariette C, Wente MN, Izbicki JR, Friess H, Lerch MM, Dervenis C, Olah A, Butturini G, Doi R, Lind PA, Smith D, Valle JW, Palmer DH, Buckels JA, Thompson J, McKay CJ, Rawcliffe CL, Buchler MW; European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1073-81. doi: 10.1001/jama.2010.1275.
citation: Jones RP, Psarelli EE, Jackson R, Ghaneh P, Halloran CM, Palmer DH, Campbell F, Valle JW, Faluyi O, O'Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ting Y, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Lerch MM, Mayerle J, Tjaden C, Strobel O, Hackert T, Buchler MW, Neoptolemos JP; European Study Group for Pancreatic Cancer. Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial. JAMA Surg. 2019 Nov 1;154(11):1038-1048. doi: 10.1001/jamasurg.2019.3337.
citation: Ghaneh P, Kleeff J, Halloran CM, Raraty M, Jackson R, Melling J, Jones O, Palmer DH, Cox TF, Smith CJ, O'Reilly DA, Izbicki JR, Scarfe AG, Valle JW, McDonald AC, Carter R, Tebbutt NC, Goldstein D, Padbury R, Shannon J, Dervenis C, Glimelius B, Deakin M, Anthoney A, Lerch MM, Mayerle J, Olah A, Rawcliffe CL, Campbell F, Strobel O, Buchler MW, Neoptolemos JP; European Study Group for Pancreatic Cancer. The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma. Ann Surg. 2019 Mar;269(3):520-529. doi: 10.1097/SLA.0000000000002557.