TeloVac

Title

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
III	Treatment	Open	Over 18	The Royal Liverpool and Broadgreen University Hospitals NHS Trust	EUDRACT No: 2006-000461-10 ISRCTN No: 43482138

Trial Description

Purpose

Telomerase is a ribonucleoprotein enzyme which is involved in the DNA replication of the cell cycle. The enzyme is over-expressed in majority of human cancers including 90% of advanced pancreatic cancer patients and therefore is a natural therapeutic target in the treatment of cancer.
The over-expression of Telomerase enables the cancer cells to overcome mortality and therefore be a major contributing factor to progression of cancer. Telomerase is one of the body's own proteins and therefore not recognised or attacked by the immune response. The GV1001 vaccine targets the over-expressed telomerase by enabling the immune response to recognise the enzyme and illicit an immune response against it. As telomerase is over expressed in majority of cancers and plays a leading role in the mortality of cancer cells, GV1001 could in future become a common cancer vaccine.

Eligibility

Age > 18 years.
Histologically or cytologically proven pancreatic ductal adenocarcinoma carcinoma or undifferentiated carcinoma of the pancreas.
Locally advanced or metastatic disease precluding curative surgical resection or patients who have relapsed following previously resected Pancreatic Cancer
Contrast enhanced CT scan of the thorax, abdomen and pelvis within 28 days prior to commencing treatment.
Unidimensionally measurable disease (CT) in accordance with the RECIST guidelines.
ECOG performance status 0, 1 or 2.
Platelets >100 x 109/l; WBC > 3 x 109/l; neutrophils > 1.5 x 109/l at entry.
Serum bilirubin < 35 mol/l
Calculated creatinine clearance over 50ml/min according to Cockcroft & Gault.
Life expectancy > 3 months.
Informed written consent.
No medical or psychiatric conditions compromising informed consent.
No intracerebral metastases or meningeal carcinomatosis.
No clinically significant serious disease or organ system disease not currently controlled on present therapy.
No uncontrolled angina pectoris.
No pregnant or breast feeding.
No previous chemotherapy for locally advanced and metastatic disease. Previously adjevent chemotherapy for resected pancreatic cancer will be permitted providing chemotherapy was completed more than 12 months previously.
No radiotherapy within the last 4 weeks prior to start of study treatment.
No concurrent malignancies or invasive cancers diagnosed within the past 5 years except for adequately treated Basal Cell Carcinoma of the skin, in situ carcinoma of the uterine cervix or resected pancreatic cancer (see No 6 of Exclusion and No 3 of Inclusion)
No known malabsorption syndromes.
No patients with a known hypersensitivity to any of the investigational products or patients with a dihydropyrimidine dehydrogenase (DPD) deficiency.
No patients on medication which might affect immunocompetence e.g. chronic treatment with long term steroids or other immunosuppressant for an unrelated condition. Patients will be eligible if they have been receiving short term steroids for palliation of cancer related symptoms.
No men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom.

Treatment/Intervention

This study is designed as a prospective, phase III, controlled, open label, multicentre, randomised clinical trial comparing combination Gemcitabine and Capecitabine therapy with concurrent and sequential immunotherapy using the telomerase vaccinne GV 1001 in locally advanced and metastatic pancreatic cancer. Patients will be treated until disease progression and will be subject to follow-up until death. Patients will be randomised equally between the three arms:

Gemcitabine & Capecitabine
Gemcitabine and Capecitabine then sequential GV1001 followed by further Gemcitabine and capecitabine for patients where no progressive disease (PD) was demonstrated upon the week 8 CT Concurrent administration of Gemcitabine and Capecitabine and GV1001.
Concurrent administration of Gemcitabine and Capecitabine and GV1001

Patients will be stratified by: Stage of disease (locally advanced vs. metastatic) and Performance status (0 versus 1 versus 2)

Target recruitment is 1110 patients (370 within each arm).

The Capecitabine will be fully funded by Roche Pharmaceuticals and will be distributed free of charge. See BJC paper-for phase I/II full paper {ref: CTN 1-2000 BJC paper.pdf}.

Trial Endpoints

Primary Outcome

Length of survival

Secondary outcomes

Time to progression
Quality of life
Clinical Benefit Response
Objective response rate
Toxicity
Survival and response by DTH
CA19-9 over time

Trial Lead Organisations

Royal Liverpool and Broadgreen University Hospitals NHS Trust
Chief Investigator: Dr Gary Middleton, Royal Surrey County Hospital NHS Trust

Trial Sites

There are now 52 sites open in the trial:

Aberdeen Royal Infirmary, Aberdeen (Dr. Marianne Nicolson)
Addenbrookes Hospital, Cambridge (Dr. Pippa Corrie)
Beatson West of Scotland Oncology Centre, Glasgow (Prof. Jeff Evans)
Belfast City Hospital, Belfast City Hospital (Dr. Martin Eatock)
Bristol Haematology and Oncology Centre,, Bristol, (Dr. Stephen Falk)
Christie Hospital, Manchester (Dr. Juan Valle)
Clatterbridge Centre for Oncology, Wirral (Dr. David Smith)
Cumberland Infirmary, Carlisle (Dr. Jonathan Nicoll)
Darent Valley Hospital, Dartford (Dr. Riyaz Shah)
Dorset County Hospital,, Dorchester (Dr. Richard Osborne)
Glan Clwyd Hospital, Rhyl (Dr. Angel Garcia)
Guys & St Thomas Hospital, London (Dr. Paul Ross)
Huddersfield Royal Infirmary, Huddersfield (Dr. Jo Dent)
Ipswich Hospital, Ipswich (Dr. Rubin Soomal)
James Paget Hospital, Great Yarmouth (Dr. Ulrike Dernedde)
Leicester Royal Infirmary, Leicester (Prof. Will Steward)
Lincoln County Hospital, Lincoln (Dr. Zuzana Stokes)
Mid Essex Hospital, Court Road (Dr. Saad Tahir)
Middlesborough, Middlesbrough (Dr. Nick Wadd)
Mount Vernon Cancer Centre, Northwood ( Mark Harrison)
Norfolk and Norwich University Hospital, Colney Lane (Dr. Tom Roques)
North Devon District Hospital, Barnstaple (Dr. Mark Napier)
North Hampshire NHS Trust, Basingstoke (Dr. Charlotte Rees)
Nottingham City Hospital, Nottingham (Prof. Srinivasan Madhusudan)
Peterborough District Hospital,, Peterborough (Dr. Karen McAdam)
Pilgrim Hospital, Boston (Dr. Zuzana Stokes)
Poole Hospital NHS Trust, Poole (Dr. Richard Osborne)
Portsmouth Haemotology & Oncology Centre, Portsmouth (Dr. Caroline Archer)
Royal Bournemouth Hospital, Bournemouth (Dr. Tamas Hickish)
Royal Cornwall Hospital, Truro (Dr. Richard Ellis)
Royal Devon and Exeter Hospital, Exeter (Dr. Elizabeth Toy)
Royal Free Hospital, London (Dr. Tim Meyer)
Royal Liverpool University Hospital, Liverpool (Dr. David Smith)
Royal Marsden Hospital, London (Prof. David Cunningham)
Royal Marsden Hospital Surrey, Sutton (Prof. David Cunningham)
Royal Surrey County Hospital, Guildford (Dr. Gary Middleton)
Salisbury District Hospital, Salisbury (Dr. Tim J Iveson)
Sir Bobby Robson Cancer Trials Research Centre, Newcastle Upon Tyne (Dr. Fareeda Coxon)
Southampton University Hospital, Southampton (Dr. Tim J Iveson)
St Georges, Tooting (Dr. Tim Benepal)
St. Bartholomew's Hospital, London (Dr. David Propper)
Sussex Cancer Research Network, St. Leonards on Sea (Dr. Angus Robinson)
Sussex Oncology Centre, Brighton (Dr. Andrew Webb)
The Churchill Hospital, Oxford (Dr. Kinnari Patel)
Torbay District General Hospital, Torquay (Dr. Rajagura Srinivasan)
West Cumberland Hospital, Carlisle (Dr. Jonathan Nicoll)
Weston General Hospital, Weston-Super-Mare ( Serena Hilman)
Weston Park Hospital, Sheffield (Dr. Jonathan C Wadsley)
Wexham Park Hospital, Slough (Dr. Marcia Hall)
Worthing Hospital, Worthing (Dr. Andrew Webb)
Wrexham Maelor Hospital, Wrexham c/oRhyl (Dr. Simon Gollins)
Yeovil District Hospital,, Yeovil (Dr. Julie Walther)

The following sites have expressed an interest:

Airedale General Hospital, Keighley (Dr. Michael Crawford)
Basildon and Thurrock University Hospital, Basildon (Dr. Pauline Leonard)
Cardiff Velindre Hospital, Cardiff (Dr. Somnath Mukherjee)
Derbyshire Royal Infirmary, Derby (Dr. Rajendra Kulkarni)
Derriford Hospital, Plymouth (Dr. Sarah Pascoe)
Gloucestershire Royal Hospital, Gloucester (Dr. Charles Candish)
Heartlands Hospital, Birmingham (Dr. Joyce Thompson)
Kent & Canterbury Hospital, Ethelbert Road (Dr. Justin Waters)
Manor Hospital, Walsall (Dr. Andrew Hartley)
Musgrove Park Hospital, Taunton (Dr. Julie Walther)
New Cross Hospital, Wolverhampton (Dr. David Ferry)
North Middlesex Hospital, London (Dr. John Bridgewater)
Queen Elizabeth Hospital, Birmingham, Birmingham, (Dr. Daniel Palmer)
Royal Berkshire Hospital, Reading (Dr. Jocelyn Adams)
Royal Preston Hospital, Preston (Dr. Ajay Mehta)
Southend University Hospital, Prittlewell Chase (Dr. Pauline Leonard)
Southport and Formby District General Hospital, Wirral (Dr. Amanda Jones)
Staffordshire General Hospital, Stafford (Dr. Fawzi Adab)
University Hospital Coventry & Warwickshire NHS Trust, Clifford Bridge Road (Dr. Sharmila Sothi)
University Hospital Of North Staffordshire,, Stoke-on-Trent Staffs (Dr. Fawzi Adab)
York District Hospital, York (Dr. David Jackson)

Registry Information

Official Title

Trial Start Date

01/05/2007

Clinical Trials