Clinical trial NCT00425360: Gemcitabine and Capecitabine With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
stage IV pancreatic cancer
duct cell adenocarcinoma of the pancreas
recurrent pancreatic cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-01-23
Enrollment: 1110
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, 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival at 1 year
Secondary outcomes:
measure: Time to progression
measure: 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
measure: Clinical benefit response
measure: Objective response rate as assessed by RECIST criteria
measure: Toxicity as assessed by NCI CTCAE version 3
measure: Survival and response as assessed by delayed-type hypersensitivity
Other outcomes:
Locations:
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Dartford Kent
country: United Kingdom
facility: Darent Valley Hospital
state: England
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Norfolk
country: United Kingdom
facility: James Paget Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Saint Leonards-on-Sea
country: United Kingdom
facility: Conquest Hospital
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Torquay Devon
country: United Kingdom
facility: Torbay Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
Study officials:
affiliation: St. Luke's Cancer Centre at Royal Surrey County Hospital
name: Gary W. Middleton
role: STUDY_CHAIR
References: