Two Chemotherapy Regimens Compared With Observation in Treating Patients With Completely Resected Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT00058201
• Recruitment Status: Completed
• First Posted: April 9, 2003
• Last Update Posted: December 18, 2013
• Sponsor: Royal Liverpool University Hospital
• Collaborators: NCIC Clinical Trials Group; Australasian Gastro-Intestinal Trials Group
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: April 7, 2003
• First Posted Date: April 9, 2003
• Last Update Posted Date: December 18, 2013
• Study Start Date: July 2001
• Actual Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 10, 2007): Overall survival
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: July 10, 2007)

• Toxicity as measured by NCI CTC v2.0
• 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
• Survival rate at 2 and 5 years

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Two Chemotherapy Regimens Compared With Observation in Treating Patients With Completely Resected Pancreatic Cancer
• Official Title: European Study Group For Pancreatic Cancer - Trial 3

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Primary Purpose: Treatment
• Condition: Pancreatic Cancer

Intervention

• Drug: fluorouracil
  Given IV
• Drug: gemcitabine hydrochloride
  Given IV
• Drug: leucovorin calcium
  Given IV
• Other: clinical observation
  No intervention

Study Arms

• Active Comparator: Arm I
  Patients receive leucovorin calcium IV and fluorouracil IV on days 1-5.
  Interventions:

  • Drug: fluorouracil
  • Drug: leucovorin calcium
• Experimental: Arm II
  Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15.
  Intervention: Drug: gemcitabine hydrochloride
• No Intervention: Arm III
  Patients undergo observation.
  Intervention: Other: clinical observation

Publications *

• 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. Erratum In: JAMA. 2012 Nov 14;308(18):1861.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: July 10, 2007): 1030
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 2010
• Actual Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czech Republic, Finland, France, Germany, Greece, Hungary, Italy, Japan, Sweden, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT00058201
• Other Study ID Numbers: CDR0000287023; RLUH-NCRI-ESPAC-3V2; EU-20043; CAN-NCIC-PA2; AGITG-ESPAC-3
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Royal Liverpool University Hospital
• Original Study Sponsor: Institute of Cancer Research, United Kingdom

Collaborators

• NCIC Clinical Trials Group
• Australasian Gastro-Intestinal Trials Group

Investigators

• Study Chair: John P. Neoptolemos, MD; Royal Liverpool University Hospital
• Study Chair: Malcolm J. Moore, MD; Princess Margaret Hospital, Canada
• Investigator: R. Padbury; Flinders Medical Centre
• Investigator: David Goldstein, MD; Institute of Oncology at Prince of Wales Hospital

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2008