A Multi-Centre, Phase Ii, Open-Label, Single Arm Study of Panitumumab, Cisplatin and Gemcitabine in Biliary Tract Cancer: Primary Results of the Agitg Tactic Study

TPS514 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m2, irinotecan of 180 mg/m2, leucovorin of 400 mg/m2 administered by intravenous infusion and fluorouracil of 400 mg/m2 by intravenous bolus and of 2,400 mg/m2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.

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

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-016-3089-4 ◽

2016 ◽

Vol 78 (2) ◽

pp. 361-367 ◽

Cited By ~ 10

Author(s):

D. Ferraro ◽

◽

D. Goldstein ◽

R. L. O’Connell ◽

J. R. Zalcberg ◽

...

Keyword(s):

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Phase Ii Trial ◽

Open Label ◽

Tract Cancer

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A phase II study of gemcitabine as adjuvant treatment for biliary tract cancer after surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.330 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 330-330 ◽

Cited By ~ 1

Author(s):

Sang Myung Woo ◽

Kyong-Ah Yoon ◽

Eun Kyung Hong ◽

Weon Seo Park ◽

Sung-Sik Han ◽

...

Keyword(s):

Biliary Tract ◽

Phase Ii ◽

Biliary Tract Cancer ◽

Vascular Invasion ◽

Phase Ii Study ◽

Cytidine Deaminase ◽

Hematologic Toxicity ◽

Open Label ◽

Extrahepatic Cholangiocarcinoma ◽

Tract Cancer

330 Background: The role of adjuvant therapy following resection of biliary tract cancer (BTC) remains unclear. We therefore evaluated the feasibility and toxicity of adjuvant gemcitabine in patients with BTC. Methods: This clinical phase II study was an open-label, single center, single-arm study. Within 8 weeks after gross complete resection of BTC, patents received gemcitabine 1000 mg/m2as an intravenous 30-min infusion on day 1, 8, and 15 for every 28 days. Intratumoral expression of cytidine deaminase (CDA), human equilibrative transporter-1 (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit 1 (RRM1) was measured by immunohistochemistry and eight SNPs in the CDA, hENT1, dCK, hCNT3 and RRM1 genes were evaluated. The relationship of each with patients’ clinical outcomes was assessed. Results: From January 2010 to July 2014, a total of 72 BTC patients (26 with gallbladder cancer, 33 with extrahepatic cholangiocarcinoma, and 13 with intrahepatic cholangiocarcinoma) were enrolled. At a median follow-up was 38.09 months (range: 4.14-68.29), 2-year recur- free survival (RFS) was 43% (95% CI, 33% to 57%). The most common grade 3 and 4 toxicity was neutropenia, which occurred in 8 patients (11%). There was one treatment-related death from pneumonitis. The Cox proportion hazard model was performed with the following nine variables; gross type, degree of tumor differentiation. pathologic T factor, N stage, vascular invasion, perineural invasion, lymphatic invasion, dosage, and each protein expression. In the multivariable model, DCK expression, vascular invasion, and lymph node metastasis, were significantly associated with RFS. None of the tested SNPs was significantly associated with RFS or with any hematologic or non-hematologic toxicity. Conclusions: Although the primary hypothesis of this study, defined as a 2-year RFS of 60%, was not met, intratumoral DCK expression was significantly associated with RFS in patients with resected BTC treated with postoperative gemcitabine chemotherapy. Future randomized controlled trials are warranted. Clinical trial information: NCT01043172.

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