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Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Middleton, Gary; Silcocks, Paul; Cox, Trevor; Valle, Juan; Wadsley, Jonathan; Propper, David; Coxon, Fareeda; Ross, Paul; Srinivasan, Madhusudan; Roques, Tom; Cunningham, David; Falk, Stephen; Wadd, Nick; Harrison, Mark; Corrie, Pippa; Iveson, Tim; Robinson, Angus; McAdam, Karen; Eatock, Martin; Evans, Jeff; Archer, Caroline; Hickish, Tamas; Garcia-Alonso, Angel; Nicolson, Marianne; Steward, William; Anthoney, D. Alan; Greenhalf, William; Shaw, Victoria E.; Costello, Eithne; Naisbitt, Dean; Rawcliffe, Charlotte; Nanson, Gemma; Neoptolemos, John P.

Authors

Gary Middleton

Paul Silcocks

Trevor Cox

Juan Valle

Jonathan Wadsley

David Propper

Fareeda Coxon

Paul Ross

Tom Roques

David Cunningham

Stephen Falk

Nick Wadd

Mark Harrison

Pippa Corrie

Tim Iveson

Angus Robinson

Karen McAdam

Martin Eatock

Jeff Evans

Caroline Archer

Tamas Hickish

Angel Garcia-Alonso

Marianne Nicolson

William Steward

D. Alan Anthoney

William Greenhalf

Victoria E. Shaw

Eithne Costello

Dean Naisbitt

Charlotte Rawcliffe

Gemma Nanson

John P. Neoptolemos



Abstract

BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.

METHODS: TeloVac was a three-group, open-label, randomised phase 3 trial. We recruited patients from 51 UK hospitals. Eligible patients were treatment naive, aged older than 18 years, with locally advanced or metastatic pancreatic ductal adenocarcinoma, and Eastern Cooperative Oncology Group performance status of 0-2. Patients were randomly assigned (1:1:1) to receive either chemotherapy alone, chemotherapy with sequential GV1001 (sequential chemoimmunotherapy), or chemotherapy with concurrent GV1001 (concurrent chemoimmunotherapy). Treatments were allocated with equal probability by means of computer-generated random permuted blocks of sizes 3 and 6 in equal proportion. Chemotherapy included six cycles of gemcitabine (1000 mg/m(2), 30 min intravenous infusion, at days 1, 8, and 15) and capecitabine (830 mg/m(2) orally twice daily for 21 days, repeated every 28 days). Sequential chemoimmunotherapy included two cycles of combination chemotherapy, then an intradermal lower abdominal injection of granulocyte-macrophage colony-stimulating factor (GM-CSF; 75 μg) and GV1001 (0·56 mg; days 1, 3, and 5, once on weeks 2-4, and six monthly thereafter). Concurrent chemoimmunotherapy included giving GV1001 from the start of chemotherapy with GM-CSF as an adjuvant. The primary endpoint was overall survival; analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN4382138.

FINDINGS: The first patient was randomly assigned to treatment on March 29, 2007, and the trial was terminated on March 27, 2011. Of 1572 patients screened, 1062 were randomly assigned to treatment (358 patients were allocated to the chemotherapy group, 350 to the sequential chemoimmunotherapy group, and 354 to the concurrent chemoimmunotherapy group). We recorded 772 deaths; the 290 patients still alive were followed up for a median of 6·0 months (IQR 2·4-12·2). Median overall survival was not significantly different in the chemotherapy group than in the sequential chemoimmunotherapy group (7·9 months [95% CI 7·1-8·8] vs 6·9 months [6·4-7·6]; hazard ratio [HR] 1·19, 98·25% CI 0·97-1·48, p=0·05), or in the concurrent chemoimmunotherapy group (8·4 months [95% CI 7·3-9·7], HR 1·05, 98·25% CI 0·85-1·29, p=0·64; overall log-rank of χ(2)2df=4·3; p=0·11). The commonest grade 3-4 toxic effects were neutropenia (68 [19%] patients in the chemotherapy group, 58 [17%] patients in the sequential chemoimmunotherapy group, and 79 [22%] patients in the concurrent chemoimmunotherapy group; fatigue (27 [8%] in the chemotherapy group, 35 [10%] in the sequential chemoimmunotherapy group, and 44 [12%] in the concurrent chemoimmunotherapy group); and pain (34 [9%] patients in the chemotherapy group, 39 [11%] in the sequential chemoimmunotherapy group, and 41 [12%] in the concurrent chemoimmunotherapy group).

INTERPRETATION: Adding GV1001 vaccination to chemotherapy did not improve overall survival. New strategies to enhance the immune response effect of telomerase vaccination during chemotherapy are required for clinical efficacy.

Journal Article Type Article
Publication Date Jul 31, 2014
Journal Lancet Oncology
Print ISSN 1470-2045
Electronic ISSN 1474-5488
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 15
Issue 8
APA6 Citation Middleton, G., Silcocks, P., Cox, T., Valle, J., Wadsley, J., Propper, D., …Neoptolemos, J. P. (2014). Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncology, 15(8), https://doi.org/10.1016/S1470-2045%2814%2970236-0
DOI https://doi.org/10.1016/S1470-2045%2814%2970236-0
Keywords Copyright Elsevier 2014.
Publisher URL http://www.sciencedirect.com/science/article/pii/S1470204514702360
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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