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

Pancreatic Cancer Clinical Trial

Official title:

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00425360
• Other study ID #: CDR0000528021
• Secondary ID: CRUK-TELOVAC-V4E
• Status: Completed
• Phase: Phase 3
• First received: January 19, 2007
• Last updated: August 23, 2013
• Start date: September 2006
• Est. completion date: March 2013

Study information

• Verified date: May 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1110
• Est. completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• sargramostim

• telomerase peptide vaccine GV1001

Drug:
• capecitabine

• gemcitabine hydrochloride

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Pilgrim Hospital	Boston	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Darent Valley Hospital	Dartford Kent	England
United Kingdom	Dorset County Hospital	Dorchester	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool University Hospital	Liverpool	England
United Kingdom	Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	James Paget Hospital	Norfolk	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Norfolk and Norwich University Hospital	Norwich	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	Churchill Hospital	Oxford	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Portsmouth Oncology Centre at Saint Mary's Hospital	Portsmouth Hants	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Conquest Hospital	Saint Leonards-on-Sea	England
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Torbay Hospital	Torquay Devon	England
United Kingdom	Royal Cornwall Hospital	Truro, Cornwall	England
United Kingdom	Worthing Hospital	Worthing	England
United Kingdom	Wrexham Maelor Hospital	Wrexham	Wales
United Kingdom	Yeovil District Hospital	Yeovil	England

Sponsors (1)

Lead Sponsor	Collaborator
Royal Liverpool University Hospital

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at 1 year			No
Secondary	Time to progression			No
Secondary	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			No
Secondary	Clinical benefit response			No
Secondary	Objective response rate as assessed by RECIST criteria			No
Secondary	Toxicity as assessed by NCI CTCAE version 3			Yes
Secondary	Survival and response as assessed by delayed-type hypersensitivity			No