Skip to main content

Advertisement

SpringerLink
Log in

TACTIC: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The phase II TACTIC trial prospectively selected patients with KRAS wild-type advanced biliary tract cancer for first-line treatment with panitumumab and combination chemotherapy.

Methods

Of 78 patients screened, 85 % had KRAS wild-type tumours and 48 were enrolled. Participants received cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8 of each 21-day cycle and panitumumab 9 mg/kg on day 1 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or request to discontinue. The primary endpoint was the clinical benefit rate (CBR) at 12 weeks (complete response, partial response, or stable disease). CBR of 70 % was considered to be of clinical interest. Secondary outcomes were progression-free survival, time to treatment failure, overall survival, CA19.9 response and safety.

Results

Thirty-four patients had a clinical benefit at 12 weeks, an actuarial rate of 80 % (95 % CI 65–89 %). 46 % had a complete or partial response. Median progression-free survival was 8.0 months (95 % CI 5.1–9.9) and median overall survival 11.9 months (95 % CI 7.4–15.8). Infection accounted for 27 % of the grade 3 or 4 toxicity, with rash (13 %), fatigue (13 %), and hypomagnesemia (10 %) among the more common grade 3 or 4 non-haematological toxicities.

Conclusion

A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wade TP, Prasad CN, Virgo KS, Johnson FE (1997) Experience with distal bile duct cancers in U.S. Veterans Affairs hospitals: 1987–1991. J Surg Oncol 64(3):242–245. doi:10.1002/(sici)1096-9098(199703)64:3<242:aid-jso12>3.0.co;2-6

    Article  CAS  PubMed  Google Scholar 

  2. Lepage C, Capocaccia R, Hackl M, Lemmens V, Molina E, Pierannunzio D, Sant M, Trama A, Faivre J (2015) Survival in patients with primary liver cancer, gallbladder and extrahepatic biliary tract cancer and pancreatic cancer in Europe 1999–2007: results of EUROCARE-5. Eur J Cancer 51(15):2169–2178. doi:10.1016/j.ejca.2015.07.034

    Article  Google Scholar 

  3. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281. doi:10.1056/nejmoa0908721

    Article  CAS  PubMed  Google Scholar 

  4. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160–1174. doi:10.1056/nejmra0707704

    Article  CAS  PubMed  Google Scholar 

  5. Gruenberger B, Schueller J, Heubrandtner U, Wrba F, Tamandl D, Kaczirek K, Roka R, Freimann-Pircher S, Gruenberger T (2010) Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol 11(12):1142–1148. doi:10.1016/s1470-2045(10)70247-3

    Article  CAS  PubMed  Google Scholar 

  6. Sohal DPS, Mykulowycz K, Uehara T, Teitelbaum UR, Damjanov N, Giantonio BJ, Carberry M, Wissel P, Jacobs-Small M, O’Dwyer PJ, Sepulveda A, Sun W (2013) A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma. Ann Oncol 24(12):3061–3065. doi:10.1093/annonc/mdt416

    Article  CAS  PubMed  Google Scholar 

  7. Jensen LH, Lindebjerg J, Ploen J, Hansen TF, Jakobsen A (2012) Phase II marker-driven trial of panitumumab and chemotherapy in KRAS wild-type biliary tract cancer. Ann Oncol 23(9):2341–2346. doi:10.1093/annonc/mds008

    Article  CAS  PubMed  Google Scholar 

  8. Lee J, Park SH, Chang HM, Kim JS, Choi HJ, Lee MA, Jang JS, Jeung HC, Kang JH, Lee HW, Shin DB, Kang HJ, Sun JM, Park JO, Park YS, Kang WK, Lim HY (2012) Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 13(2):181–188. doi:10.1016/s1470-2045(11)70301-1

    Article  CAS  PubMed  Google Scholar 

  9. Goldstein D, Gainford MC, Brown C, Tebbutt N, Ackland SP, van Hazel G, Jefford M, Abdi E, Selva-Nayagam S, Gebski V, Miller D, Shannon J (2010) Fixed-dose-rate gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. Cancer Chemother Pharmacol 67(3):519–525. doi:10.1007/s00280-010-1351-8

    Article  PubMed  Google Scholar 

  10. Meyerhardt JA, Zhu AX, Stuart K, Ryan DP, Blaszkowsky L, Lehman N, Earle CC, Kulke MH, Bhargava P, Fuchs CS (2007) Phase-II study of gemcitabine and cisplatin in patients with metastatic biliary and gallbladder cancer. Dig Dis Sci 53(2):564–570. doi:10.1007/s10620-007-9885-2

    Article  PubMed  Google Scholar 

  11. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10(1):1–10. doi:10.1016/0197-2456(89)90015-9

    Article  CAS  PubMed  Google Scholar 

  12. Korn EL, Graubard BI (1999) Analysis of health surveys. Wiley, Blackwell, New York. doi:10.1002/9781118032619

    Book  Google Scholar 

  13. Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17(4):343–346. doi:10.1016/0197-2456(96)00075-x

    Article  CAS  PubMed  Google Scholar 

  14. Clark TG, Altman DG, Stavola BLD (2002) Quantification of the completeness of follow-up. Lancet 359(9314):1309–1310. doi:10.1016/s0140-6736(02)08272-7

    Article  PubMed  Google Scholar 

  15. Malka D, Cervera P, Foulon S, Trarbach T, de la Fouchardière C, Boucher E, Fartoux L, Faivre S, Blanc J-F, Viret F, Assenat E, Seufferlein T, Herrmann T, Grenier J, Hammel P, Dollinger M, André T, Hahn P, Heinemann V, Rousseau V, Ducreux M, Pignon J-P, Wendum D, Rosmorduc O, Greten TF (2014) Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Lancet Oncol 15(8):819–828. doi:10.1016/s1470-2045(14)70212-8

    Article  CAS  PubMed  Google Scholar 

  16. Valle JW (2014) BINGO: targeted therapy for advanced biliary-tract cancer. Lancet Oncol 15(8):778–780. doi:10.1016/s1470-2045(14)70238-4

    Article  PubMed  Google Scholar 

  17. Chen JS, Hsu C, Chiang NJ, Tsai CS, Tsou HH, Huang SF, Bai LY, Chang IC, Shiah HS, Ho CL, Yen CJ, Lee KD, Chiu CF, Rau KM, Yu MS, Yang Y, Hsieh RK, Chang JY, Shan YS, Chao Y, Chen LT, Taiwan Cooperative Oncology G, Shen WC, Hsu HC, Hsu CH, Shen YC, Wang TE, Li CP, Chen MH, Kao WY, Chang PY, Wu CC, Teng CL, Lu CH, Lin SJ, Wang BW, Chen YY, Chin YH, Chung TR, Yu WL, Lee MH, Lin LF, Lin PC, Wu YL, Wang HL, Lu LJ, Chen SY, Wu CC, Wei TC (2015) A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer. Ann Oncol 26(5):943–949. doi:10.1093/annonc/mdv035

    Article  CAS  PubMed  Google Scholar 

  18. Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS (2014) Extended RAS mutations and anti-EGFR monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized, controlled trials. Ann Oncol 26(1):13–21. doi:10.1093/annonc/mdu378

    Article  PubMed  Google Scholar 

  19. Yang Z-Y, Wu X-Y, Huang Y-F, Di M-Y, Zheng D-Y, Chen J-Z, Ding H, Mao C, Tang J-L (2013) Promising biomarkers for predicting the outcomes of patients with KRAS wild-type metastatic colorectal cancer treated with anti-epidermal growth factor receptor monoclonal antibodies: a systematic review with meta-analysis. Int J Cancer 133(8):1914–1925. doi:10.1002/ijc.28153

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank John Simes for helpful comments and Rhana Pike for assistance with the manuscript.

Funding

This work was supported by an unrestricted educational grant provided by Amgen.

TACTIC

Trial Management Committee

J Shannon (Chair), D Goldstein, N Tebbutt, S Ng, M Cronk, C Karapetis, K Sjoquist, C Aiken

Independent Data Safety Monitoring Committee

VDo (Chair), I Marschner, M Friedlander, H Gurney

Clinical Trials Centre

J Simes, W Hague, R O’Connell, V Gebski, C Aiken, M Gorzeman, R Pike, K Miranda

Centre for Translational Pathology

P Waring, D Ferraro

Olivia Newton-John Cancer Research Institute

D Lau

Peter MacCallum Cancer Centre

S Fox

The following study sites participated in the [TACTIC] study and randomized at least one patient (principal investigator and site coordinator)

Austin Health, Victoria—N Tebbutt, Y Liu

Concord RG Hospital, New South Wales—P Beale, R Wykes

Icon Cancer Care, Queensland—P Vasey, T Wood

Nambour General Hospital, Queensland—M Cronk, C Cocks/K Simmons

Nepean Hospital, New South Wales—J Shannon, J McCourt

Peter MacCallum Cancer Centre, Victoria—M Jefford, A Hobinchet

Royal Prince Alfred Hospital, New South Wales—P Grimison, B Mirco/J Sagong

Sir Charles Gairdner Hospital, Western Australia—S Ng, S Dudukovic

Southern Medical Day Care Centre, New South Wales—M Aghmesheh, S Parker

St Vincent’s Hospital, New South Wales—E Segelov, L Ratnayake

St Vincent’s Hospital, Victoria—S McLachlan, N Ranieri

Townsville Hospital, Queensland—S Varma, J Page/E Heyer

Tweed Hospital, New South Wales—E Abdi, C Chorlton

Western Health, Victoria—L Lipton, L Wilkinson/I Marshall

Author information

Authors and Affiliations

  1. National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia

    D. Ferraro, R. L. O’Connell, K. M. Sjoquist, V. J. Gebski & C. Aiken

  2. Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia

    D. Goldstein

  3. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    J. R. Zalcberg

  4. Austin Health, Melbourne, VIC, Australia

    N. C. Tebbutt

  5. Chris O’Brien Lifehouse, Sydney, NSW, Australia

    P. Grimison

  6. St Vincents Hospital, Melbourne, VIC, Australia

    S. McLachlan

  7. University of Melbourne, Melbourne, VIC, Australia

    S. McLachlan

  8. Western Health, Melbourne, VIC, Australia

    L. L. Lipton

  9. Haematology and Oncology Clinics of Australasia, Wesley Medical Centre, Brisbane, QLD, Australia

    P. Vasey

  10. Nambour General Hospital, Nambour, QLD, Australia

    M. Cronk

  11. Flinders University, Adelaide, SA, Australia

    C. S. Karapetis

  12. Department of Medical Oncology, Nepean Cancer Care Centre, PO Box 63, Penrith, Sydney, NSW, 2751, Australia

    J. Shannon

  13. Department of Pathology, University of Melbourne, Parkville, VIC, Australia

    D. Ferraro

  14. Sir Charles Gairdner Hospital, Nedlands, WA, Australia

    S. Ng

Authors
  1. D. Ferraro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. L. O’Connell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. R. Zalcberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. M. Sjoquist
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. C. Tebbutt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Grimison
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. McLachlan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L. L. Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. Vasey
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V. J. Gebski
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. C. Aiken
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. Cronk
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S. Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C. S. Karapetis
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. J. Shannon
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

behalf of the the Australasian Gastro-Intestinal Trials Group

  • J. Shannon
  • , D. Goldstein
  • , N. Tebbutt
  • , S. Ng
  • , M. Cronk
  • , C. Karapetis
  • , K. Sjoquist
  • , C. Aiken
  • , V. Do
  • , I. Marschner
  • , M. Friedlander
  • , H. Gurney
  • , J. Simes
  • , W. Hague
  • , R. O’Connell
  • , V. Gebski
  • , C. Aiken
  • , M. Gorzeman
  • , R. Pike
  • , K Miranda
  • , P. Waring
  • , D. Ferraro
  • , D. Lau
  • , S. Fox
  • , N. Tebbutt
  • , Y. Liu
  • , P. Vasey
  • , T. Wood
  • , M. Cronk
  • , C. Cocks
  • , K. Simmons
  • , J. Shannon
  • , J. McCourt
  • , M. Jefford
  • , A. Hobinchet
  • , P. Grimison
  • , B. Mirco
  • , J. Sagong
  • , S. Ng
  • , S. Dudukovic
  • , M. Aghmesheh
  • , S. Parker
  • , E. Segelov
  • , L. Ratnayake
  • , S. McLachlan
  • , N. Ranieri
  • , S. Varma
  • , J. Page
  • , E. Heyer
  • , E. Abdi
  • , C. Chorlton
  • , L. Lipton
  •  & L. Wilkinson

Corresponding author

Correspondence to J. Shannon.

Ethics declarations

Conflict of interest

DG: research funding, Celgene Corporation, Amgen, Pfizer and Glaxo Smith Kline; JRZ: honoraria, financial support for attending symposia and research funding, Amgen, Merck Serono; CSK: advisory role with Amgen; NCT: research funding by Amgen. All remaining authors have declared no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferraro, D., Goldstein, D., O’Connell, R.L. et al. TACTIC: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. Cancer Chemother Pharmacol 78, 361–367 (2016). https://doi.org/10.1007/s00280-016-3089-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-016-3089-4

Keywords

Search

Navigation