Gemcitabine and Capecitabine With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

A Prospective, Phase III, Controlled, Multicentre, Randomised Clinical Trial Comparing Combination Gemcitabine and Capecitabine Therapy With Concurrent and Sequential Chemoimmunotherapy Using a Telomerase Vaccine in Locally Advanced and Metastatic Pancreatic Cancer [TELOVAC]

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving more than one drug (combination chemotherapy) together with vaccine therapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective with or without vaccine therapy in treating pancreatic cancer.

PURPOSE: This randomized phase III trial is studying gemcitabine, capecitabine, and vaccine therapy to see how well they work compared with gemcitabine and capecitabine alone in treating patients with locally advanced or metastatic pancreatic cancer.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: capecitabine; Biological: sargramostim; Biological: telomerase peptide vaccine GV1001

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of telomerase peptide vaccine GV1001 when administered concurrently or sequentially with gemcitabine hydrochloride and capecitabine, in terms of survival, in patients with locally advanced or metastatic pancreatic cancer.

Secondary

• Determine the safety of this regimen in these patients.
• Assess the immunogenicity of this regimen in these patients.
• Determine the time to progression in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.
• Determine the clinical benefit response in patients treated with this regimen.
• Determine the objective response rate in patients treated with this regimen.
• Determine the toxicity of this regimen in these patients.
• Determine the survival and response by delayed-type hypersensitivity in patients treated with this regimen.

OUTLINE: This is a prospective, controlled, randomized, open-label, multicenter study. Patients are stratified according to stage of disease (locally advanced vs metastatic) and ECOG performance status (0 vs 1 vs 2). Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and oral capecitabine twice daily on days 1-21. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive gemcitabine hydrochloride and capecitabine as in arm I. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive sargramostim (GM-CSF) intradermally (ID) and telomerase peptide vaccine GV1001 ID on days 1, 3, and 5 in week 9, once a week in weeks 10-12 and 14, and then once a month in the absence of disease progression or unacceptable toxicity. Patients who develop disease progression while on vaccine therapy, discontinue vaccine therapy and then restart treatment with gemcitabine hydrochloride and capecitabine. Patients receive gemcitabine hydrochloride and capecitabine as above and continue treatment in the absence of further disease progression or unacceptable toxicity.
• Arm III: Patients receive gemcitabine hydrochloride and capecitabine as in arm I. Patients also receive GM-CSF ID and telomerase peptide vaccine GV1001 ID on days 1, 3, and 5 in week 1, once weekly in weeks 2, 3, 4 and 6, and then once a month in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at 8 weeks and then every 12 weeks during study treatment.

After completion of study treatment, patients are followed every 3 months.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 1,110 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 1110
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Barnstaple, England, United Kingdom, EX31 4JB
      • North Devon District Hospital
    • Basingstoke, England, United Kingdom, RG24 9NA
      • Basingstoke and North Hampshire NHS Foundation Trust
    • Boston, England, United Kingdom, PE21 9QT
      • Pilgrim Hospital
    • Bournemouth, England, United Kingdom, BH7 7DW
      • Royal Bournemouth Hospital
    • Brighton, England, United Kingdom, BN2 5BE
      • Sussex Cancer Centre at Royal Sussex County Hospital
    • Bristol, England, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
    • Cambridge, England, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital
    • Dartford Kent, England, United Kingdom, DA2 8DA
      • Darent Valley Hospital
    • Dorchester, England, United Kingdom, DT1 2JY
      • Dorset County Hospital
    • Exeter, England, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital
    • Guildford, England, United Kingdom, GU2 7XX
      • St. Luke's Cancer Centre at Royal Surrey County Hospital
    • Huddersfield, West Yorks, England, United Kingdom, HD3 3EA
      • Huddersfield Royal Infirmary
    • Ipswich, England, United Kingdom, IP4 5PD
      • Ipswich Hospital
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Liverpool, England, United Kingdom, L7 8XP
      • Royal Liverpool University Hospital
    • London, England, United Kingdom, SW17 0QT
      • St. George's Hospital
    • London, England, United Kingdom, EC1A 7BE
      • Saint Bartholomew's Hospital
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden - London
    • London, England, United Kingdom, SE5 9NU
      • Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital
    • Merseyside, England, United Kingdom, CH63 4JY
      • Clatterbridge Centre for Oncology
    • Middlesbrough, England, United Kingdom, TS4 3BW
      • James Cook University Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
      • Northern Centre for Cancer Treatment at Newcastle General Hospital
    • Norfolk, England, United Kingdom, NR31 6LA
      • James Paget Hospital
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre at Mount Vernon Hospital
    • Norwich, England, United Kingdom, NR4 7UY
      • Norfolk and Norwich University Hospital
    • Nottingham, England, United Kingdom, NG5 1PB
      • Nottingham City Hospital
    • Oxford, England, United Kingdom, OX3 7LJ
      • Churchill Hospital
    • Peterborough, England, United Kingdom, PE3 6DA
      • Peterborough Hospitals Trust
    • Poole Dorset, England, United Kingdom, BH15 2JB
      • Dorset Cancer Centre
    • Portsmouth Hants, England, United Kingdom, PO3 6AD
      • Portsmouth Oncology Centre at Saint Mary's Hospital
    • Saint Leonards-on-Sea, England, United Kingdom, TN37 7RD
      • Conquest Hospital
    • Salisbury, England, United Kingdom, SP2 8BJ
      • Salisbury District Hospital
    • Sheffield, England, United Kingdom, S10 2SJ
      • Cancer Research Centre at Weston Park Hospital
    • Slough, Berkshire, England, United Kingdom, SL2 4HL
      • Wexham Park Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden - Surrey
    • Torquay Devon, England, United Kingdom, TQ2 7AA
      • Torbay Hospital
    • Truro, Cornwall, England, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
    • Worthing, England, United Kingdom, BN11 2DH
      • Worthing Hospital
    • Yeovil, England, United Kingdom, BA21 4AT
      • Yeovil District Hospital
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Aberdeen Royal Infirmary
    • Glasgow, Scotland, United Kingdom, G11 6NT
      • Beatson West of Scotland Cancer Centre
  • Wales
    • Rhyl, Denbighshire, Wales, United Kingdom, LL 18 5UJ
      • Glan Clwyd Hospital
    • Wrexham, Wales, United Kingdom, LL13 7TD
      • Wrexham Maelor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic ductal adenocarcinoma or undifferentiated carcinoma of the pancreas

  • Locally advanced or metastatic disease precluding curative surgical resection
• Unidimensionally measurable disease by CT scan
• No intracerebral metastases or meningeal carcinomatosis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• WBC > 3,000/mm³
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Bilirubin < 2.0 mg/dL
• Creatinine clearance > 50 mL/min
• No medical or psychiatric condition that would preclude giving informed consent
• No clinically significant serious disease or organ system disease not currently controlled on present therapy
• No uncontrolled angina pectoris
• Not pregnant or nursing
• Fertile patients must use a condom and ≥ 1 other form of contraception during and for 1 year after completion of study treatment
• No other malignancies or invasive cancers within the past 5 years except for adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
• No known malabsorption syndrome
• No known hypersensitivity to any of the investigational agents
• No dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No radiotherapy within the past 4 weeks

• No concurrent medications that could affect immunocompetence (e.g., chronic treatment with long-term steroids or other immunosuppressants for unrelated condition)

  • Concurrent short-term steroids for palliation of cancer-related symptoms allowed
• No other concurrent investigational drugs or cytotoxic agents

• No other concurrent immunotherapy (e.g., immunosuppressants or chronic use of systemic corticosteroids) or chemotherapy for another tumor in patients receiving telomerase peptide vaccine GV1001

  • Concurrent low-dose corticosteroids may be allowed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Survival at 1 year

Secondary Outcome Measures

Outcome Measure
Time to progression
Objective response rate as assessed by RECIST criteria
Quality of life as assessed by the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life (QLQ) C30 questionnaire and the European Study group for Pancreatic Cancer-QLQ questionnaire
Clinical benefit response
Toxicity as assessed by NCI CTCAE version 3
Survival and response as assessed by delayed-type hypersensitivity

Collaborators and Investigators

• Sponsor: Royal Liverpool University Hospital
• Investigators: Study Chair: Gary W. Middleton, St. Luke's Cancer Centre at Royal Surrey County Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: January 19, 2007
• First Submitted That Met QC Criteria: January 19, 2007
• First Posted (Estimate): January 23, 2007

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: May 1, 2009

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; stage IV pancreatic cancer; stage III pancreatic cancer; duct cell adenocarcinoma of the pancreas
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Capecitabine; Sargramostim
• Other Study ID Numbers: CDR0000528021; CRUK-TELOVAC-V4; EUDRACT-2006-000461-10; EU-20683; ISRTCN43482138