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

D. Ferraro, D. Goldstein, R. L. O’Connell, J. R. Zalcberg, K. M. Sjoquist, N. C. Tebbutt, P. Grimison, S. McLachlan, L. L. Lipton, P. Vasey, V. J. Gebski, C. Aiken, M. Cronk, S. Ng, C. S. Karapetis, J. Shannon, J. Shannon, N. Tebbutt, S. Ng, M. Cronk & 48 others 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

Research output: Contribution to journalArticleResearchpeer-review

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/m2and gemcitabine 1000 mg/m2on 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.

LanguageEnglish
Pages361-367
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume78
Issue number2
DOIs
Publication statusPublished - 1 Aug 2016
Externally publishedYes

Fingerprint

gemcitabine
Biliary Tract Neoplasms
Cisplatin
Toxicity
Labels
Disease-Free Survival
Chemotherapy
Survival
Exanthema
Combination Drug Therapy
Treatment Failure
Patient Selection
Population
Fatigue
Disease Progression
Tumors
Neoplasms
Therapeutics
Fatigue of materials
Safety

Keywords

  • Biliary tract cancer
  • Cancer antigen 19.9
  • Chemotherapy
  • KRAS
  • Panitumumab
  • Phase II trial

Cite this

Ferraro, D., Goldstein, D., O’Connell, R. L., Zalcberg, J. R., Sjoquist, K. M., Tebbutt, N. C., ... Wilkinson, L. (2016). Tactic: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. Cancer Chemotherapy and Pharmacology, 78(2), 361-367. https://doi.org/10.1007/s00280-016-3089-4
Ferraro, D. ; Goldstein, D. ; O’Connell, R. L. ; Zalcberg, J. R. ; Sjoquist, K. M. ; Tebbutt, N. C. ; Grimison, P. ; McLachlan, S. ; Lipton, L. L. ; Vasey, P. ; Gebski, V. J. ; Aiken, C. ; Cronk, M. ; Ng, S. ; Karapetis, C. S. ; Shannon, J. ; Shannon, J. ; Tebbutt, N. ; Ng, S. ; Cronk, M. ; Karapetis, C. ; Sjoquist, K. ; Aiken, C. ; Do, V. ; Marschner, I. ; Friedlander, M. ; Gurney, H. ; Simes, J. ; Hague, W. ; O’Connell, R. ; Gebski, V. ; Aiken, C. ; Gorzeman, M. ; Pike, R. ; Miranda, K. ; Waring, P. ; Ferraro, D. ; Lau, D. ; Fox, S. ; Tebbutt, N. ; Liu, Y. ; Vasey, P. ; Wood, T. ; Cronk, M. ; Cocks, C. ; Simmons, K. ; Shannon, J. ; McCourt, J. ; Jefford, M. ; Hobinchet, A. ; Grimison, P. ; Mirco, B. ; Sagong, J. ; Ng, S. ; Dudukovic, S. ; Aghmesheh, M. ; Parker, S. ; Segelov, E. ; Ratnayake, L. ; McLachlan, S. ; Ranieri, N. ; Varma, S. ; Page, J. ; Heyer, E. ; Abdi, E. ; Chorlton, C. ; Lipton, L. ; Wilkinson, L. / Tactic : a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. In: Cancer Chemotherapy and Pharmacology. 2016 ; Vol. 78, No. 2. pp. 361-367.
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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/m2and gemcitabine 1000 mg/m2on 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.",
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Ferraro, D, Goldstein, D, O’Connell, RL, Zalcberg, JR, Sjoquist, KM, Tebbutt, NC, Grimison, P, McLachlan, S, Lipton, LL, Vasey, P, Gebski, VJ, Aiken, C, Cronk, M, Ng, S, Karapetis, CS, Shannon, J, Shannon, J, Tebbutt, N, Ng, S, Cronk, M, Karapetis, C, Sjoquist, K, Aiken, C, Do, V, Marschner, I, Friedlander, M, Gurney, H, Simes, J, Hague, W, O’Connell, R, Gebski, V, Aiken, C, Gorzeman, M, Pike, R, Miranda, K, Waring, P, Ferraro, D, Lau, D, Fox, S, Tebbutt, N, Liu, Y, Vasey, P, Wood, T, Cronk, M, Cocks, C, Simmons, K, Shannon, J, McCourt, J, Jefford, M, Hobinchet, A, Grimison, P, Mirco, B, Sagong, J, Ng, S, Dudukovic, S, Aghmesheh, M, Parker, S, Segelov, E, Ratnayake, L, McLachlan, S, Ranieri, N, Varma, S, Page, J, Heyer, E, Abdi, E, Chorlton, C, Lipton, L & Wilkinson, L 2016, 'Tactic: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer', Cancer Chemotherapy and Pharmacology, vol. 78, no. 2, pp. 361-367. https://doi.org/10.1007/s00280-016-3089-4

Tactic : a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer. / Ferraro, D.; Goldstein, D.; O’Connell, R. L.; Zalcberg, J. R.; Sjoquist, K. M.; Tebbutt, N. C.; Grimison, P.; McLachlan, S.; Lipton, L. L.; Vasey, P.; Gebski, V. J.; Aiken, C.; Cronk, M.; Ng, S.; Karapetis, C. S.; Shannon, J.; Shannon, J.; Tebbutt, N.; Ng, S.; Cronk, M.; Karapetis, C.; Sjoquist, K.; Aiken, C.; Do, V.; Marschner, I.; Friedlander, M.; Gurney, H.; Simes, J.; Hague, W.; O’Connell, R.; Gebski, V.; Aiken, C.; Gorzeman, M.; Pike, R.; Miranda, K.; Waring, P.; Ferraro, D.; Lau, D.; Fox, S.; Tebbutt, N.; Liu, Y.; Vasey, P.; Wood, T.; Cronk, M.; Cocks, C.; Simmons, K.; Shannon, J.; McCourt, J.; Jefford, M.; Hobinchet, A.; Grimison, P.; Mirco, B.; Sagong, J.; Ng, S.; Dudukovic, S.; Aghmesheh, M.; Parker, S.; Segelov, E.; Ratnayake, L.; McLachlan, S.; Ranieri, N.; Varma, S.; Page, J.; Heyer, E.; Abdi, E.; Chorlton, C.; Lipton, L.; Wilkinson, L.

In: Cancer Chemotherapy and Pharmacology, Vol. 78, No. 2, 01.08.2016, p. 361-367.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Tactic

T2 - Cancer Chemotherapy and Pharmacology

AU - Ferraro, D.

AU - Goldstein, D.

AU - O’Connell, R. L.

AU - Zalcberg, J. R.

AU - Sjoquist, K. M.

AU - Tebbutt, N. C.

AU - Grimison, P.

AU - McLachlan, S.

AU - Lipton, L. L.

AU - Vasey, P.

AU - Gebski, V. J.

AU - Aiken, C.

AU - Cronk, M.

AU - Ng, S.

AU - Karapetis, C. S.

AU - Shannon, J.

AU - Shannon, J.

AU - Tebbutt, N.

AU - Ng, S.

AU - Cronk, M.

AU - Karapetis, C.

AU - Sjoquist, K.

AU - Aiken, C.

AU - Do, V.

AU - Marschner, I.

AU - Friedlander, M.

AU - Gurney, H.

AU - Simes, J.

AU - Hague, W.

AU - O’Connell, R.

AU - Gebski, V.

AU - Aiken, C.

AU - Gorzeman, M.

AU - Pike, R.

AU - Miranda, K.

AU - Waring, P.

AU - Ferraro, D.

AU - Lau, D.

AU - Fox, S.

AU - Tebbutt, N.

AU - Liu, Y.

AU - Vasey, P.

AU - Wood, T.

AU - Cronk, M.

AU - Cocks, C.

AU - Simmons, K.

AU - Shannon, J.

AU - McCourt, J.

AU - Jefford, M.

AU - Hobinchet, A.

AU - Grimison, P.

AU - Mirco, B.

AU - Sagong, J.

AU - Ng, S.

AU - Dudukovic, S.

AU - Aghmesheh, M.

AU - Parker, S.

AU - Segelov, E.

AU - Ratnayake, L.

AU - McLachlan, S.

AU - Ranieri, N.

AU - Varma, S.

AU - Page, J.

AU - Heyer, E.

AU - Abdi, E.

AU - Chorlton, C.

AU - Lipton, L.

AU - Wilkinson, L.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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/m2and gemcitabine 1000 mg/m2on 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.

AB - 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/m2and gemcitabine 1000 mg/m2on 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.

KW - Biliary tract cancer

KW - Cancer antigen 19.9

KW - Chemotherapy

KW - KRAS

KW - Panitumumab

KW - Phase II trial

UR - http://www.scopus.com/inward/record.url?scp=84975474553&partnerID=8YFLogxK

U2 - 10.1007/s00280-016-3089-4

DO - 10.1007/s00280-016-3089-4

M3 - Article

VL - 78

SP - 361

EP - 367

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

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ER -