A phase II trial of modified gemcitabine plus S-1 combination as the first-line treatment in patients with advanced biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 417-417
Author(s):  
Nai-Jung Chiang ◽  
Jen-Shi Chen ◽  
Ming-Huang Chen ◽  
Shih-Hung Yang ◽  
Chiun Hsu ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Null Hypothesis ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standard Regimen ◽  
Tract Cancer ◽  
To Receive

417 Background: Gemcitabine plus platinum, notably cisplatin, is conceived as the standard regimen for advanced biliary tract cancer (ABTC) nowadays. Recent randomized phase II study (JCOG0805) showed that gemcitabine plus S-1 was more promising than S-1 alone in ABTC, and a randomized phase III, UMIN 000001685, is currently ongoing to compare the efficacy of gemcitabine plus either S-1 (GS) or cisplatin (GC) in ABTC. Herein, we report the results of a single arm phase II of modified GS in Taiwanese ABTC patients, NCT02425137. Methods: Patients with chemonaïve ABTC were eligible to receive 800mg/m2 gemcitabine with 10 mg/m2/min infusion, on day 1 plus daily 80/100/120 mg of S-1 (based on BSA) days 1-10, in a 2-week cycle. With Optimal Simon’s two-stage design and (p0= 0.4, p1= 0.6) for 12-week disease control rate (proportion of patients with complete or partial response [CR/PR] or stable disease ≥ 12 weeks [SD≥ 12weeks]) and given error probabilities (alpha = 0.05, beta = 0.2), the null hypothesis (p0) would be rejected if 24 or more patients with CR/PR/SD≥ 12weeks were observed among 46 accruals. Tumor response was assessed by CT/MRI every 6 weeks according to RECIST v1.1. Results: Between May 2015 and April 2016, totally 46 evaluable patients were enrolled to receive a median of 9.5 cycles (range: 3-31) of modified GS. After a median of 8.7 months (95% CI, 6.7-9.1) follow-up, 10 (21.7%) patients achieved PR and additional 23 (50%) had SD>12weeks. The median progression-free survival and overall survival was 5.6 (95% CI, 4.4-7.2) and 10.8 (95% CI, 7.6-not reached) months, respectively. All grade 3 treatment-related AEs were < 5%. The dose intensity of S-1 and gemcitabine were both more than 95%. Conclusions: By the observation of 33 patients with PR/SD≥ 12weeks, the null hypothesis was rejected. Modified GS is an active regimen with excellent safety profiles and deserves further investigation for the management of Asian ABTC patients. Clinical trial information: NCT 02425137.

scholarly journals Treatment of Patients with Advanced Biliary Tract Cancer with Either Oxaliplatin, Gemcitabine, and Capecitabine or Cisplatin and Gemcitabine—A Randomized Phase II Trial

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1975
Author(s):  
Alice Markussen ◽  
Lars Henrik Jensen ◽  
Laura Vittrup Diness ◽  
Finn Ole Larsen
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Median Overall Survival ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Tract Cancer ◽  
Randomized Phase Ii

This study is an investigator-initiated randomized phase II trial focusing on the treatment of advanced biliary tract cancer with either oxaliplatin 50 mg/m2 and gemcitabine 1000 mg/m2 on day 1 in a two-week cycle with capecitabine 650 mg/m2 twice-daily continuously or cisplatin 25 mg/m2 and gemcitabine 1000 mg/m2 on day 1 and day 8 in a three-week cycle. One-hundred patients were included. Forty-seven patients received oxaliplatin, gemcitabine, and capecitabine with a median progression-free survival (mPFS) of 5.7 months (95% CI 3.0–7.8) and a median overall survival (mOS) of 8.7 months (95% CI 6.5–11.2). Forty-nine patients received cisplatin and gemcitabine with a mPFS of 7.3 months (95% CI 6.0–8.7) and a mOS of 12.0 months (95% CI 8.3–16.7). This trial confirms a mOS of 12 months with cisplatin and gemcitabine, as found in earlier trials. With a superior tumor control rate of 79% vs. 60% (p = 0.045), a difference in the mPFS of 1.6 months (HR = 0.721, p = 0.1), and a difference in the mOS of 3.3 months (HR = 0.731, p = 0.1), cisplatin and gemcitabine should still be considered the standard first-line treatment for advanced biliary tract cancer.

Comparing the treatment outcomes between unresectable and recurrent cases receiving gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer: Pooled analysis of two prospective studies.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 331-331 ◽  
Author(s):  
Takashi Sasaki ◽  
Hiroyuki Isayama ◽  
Yukiko Ito ◽  
Ichiro Yasuda ◽  
Nobuo Toda ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Biliary Tract ◽  
Phase Ii ◽  
Combination Chemotherapy ◽  
Biliary Tract Cancer ◽  
Prospective Studies ◽  
Tumor Volume ◽  
Phase Ii Study ◽  
Dose Intensity ◽  
Tract Cancer

331 Background: We previously conducted two prospective studies (phase II study and randomized phase II study) of gemcitabine (GEM) and S-1 combination chemotherapy. The purpose of this study was to clarify the difference of treatment outcomes between unresectable and recurrent cases receiving GEM/S-1 combination chemotherapy in patients with advanced biliary tract cancer. Methods: The data of two prospective studies were combined for the analysis. In these studies, GEM was administered intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 15, repeated every four weeks. S-1 was administered orally at a dose of 40 mg/m2 b.i.d. on days 1-14. Tumor response was assessed every two cycles using RECIST version 1.0. The treatment was continued until disease progression, unacceptable toxicity or patient refusal occurred. Results: Fifty-five unresectable cases and ten recurrent cases were enrolled in this analysis. Patient characteristics were similar between each group except the baseline sum of longest diameter, which was used as a measurement of tumor volume (unresectable 9.0 cm vs recurrent 2.8 cm). Response rates of unresectable and recurrent cases were 25.5% and 40.0%, respectively. Dose intensities of each group were statistically different (gemcitabine 96.8% vs 83.5%, p=0.03; S-1 91.8% vs 75.9%, p=0.03). The median time-to-progressions of unresectable and recurrent cases were 5.7 months and 8.7 months, respectively (p=0.14). The overall survivals of each group were 9.6 months and 16.1 months (p=0.10). Conclusions: In recurrent cases, tumor volume was smaller and dose intensity was lower than that of unresectable cases. Recurrent cases showed better treatment outcome comparing to unresectable cases. Therefore, unresectable and recurrent cases should be analyzed separately in the future study.

Effectiveness study of gemcitabine, oxaliplatin, and capecitabine as first-line treatment for nonresectable biliary tract cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 334-334
Author(s):  
Lars Henrik Jensen ◽  
Anne Haahr Mellergaard ◽  
Dan Hoegdall ◽  
Ole Larsen
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Pivotal Phase ◽  
Tract Cancer ◽  
Gemcitabine And Cisplatin

334 Background: Since 2010, the doublet gemcitabine and cisplatin has been standard first-line systemic treatment for non-resectable biliary tract cancer. In a phase I-II trial of the well-tolerated triplet of gemcitabine, oxaliplatin, and capecitabine, the median progression free survival (PFS) and overall survival (OS) were 6.9 and 12.5 months, respectively. Overall response rate was 34%. Since 2005 the regimen has been used in Denmark. We wanted to investigate the effectiveness of the triplet regimen given in daily clinic. Methods: We included 192 patients from two institutions. Patients had to have non-resectable biliary tract cancer and to be suitable for combination chemotherapy on doctor’s discretion. Gemcitabine 1000 mg/m2 and oxaliplatin 60 mg/m2 were given every two weeks followed by capecitabine 1000 mg/m2 b.i.d. for one week. At one institution the oxaliplatin dose was 50 mg/m2 and capecitabine dose 650 mg/m2 b.i.d. continuously. One cycle included two treatments and was typically administered for up to six cycles/months, but was allowed for longer time until progression. Results: At institution A, 117 patients were included and 73 (62%) were women. Median age was 66 years (range 25-80). Median treatment duration was six cycles/months (range 1-12). Thirty-five, 69, 12, and one patient(s) were in performance status 0, 1, 2, and 3, respectively. Ninety patients were evaluable for response and 6 (7%) had complete response, 18 (20%) partial response, 53 (59%) stable disease, and 13 (14%) progression as best response. Median PFS was 9.7 months (95% CI 8.5-11.7) and median OS 11.7 months (9.8-14.0). The results were comparable to institution B, where the response rate in 56 patients with measurable disease was 30%. In 75 patients evaluable for survival analysis, PFS was 8.1 months and OS 12.0 months for performance status 0-1 (n=55). Patients in performance status 2 (n=25) had a PFS and OS of only 1.7 and 2.8 months, respectively. Conclusions: A triplet of gemcitabine, oxaliplatin, and capecitabine given in daily clinic was well tolerated and has effectiveness comparable to results from a phase II trial and the pivotal phase III trial of gemcitabine and cisplatin.

A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS514-TPS514 ◽  
Author(s):  
Naminatsu Takahara ◽  
Hiroyuki Isayama ◽  
Yousuke Nakai ◽  
Tatsuya Ioka ◽  
Masashi Kanai ◽  
...  
Keyword(s):  
Disease Progression ◽  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Intravenous Infusion ◽  
Tumor Response ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Open Label ◽  
Tract Cancer

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.

The influence of renal function on gemcitabine-based chemotherapy for advanced biliary tract cancer: An exploratory subgroup analysis of JCOG1113.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 368-368
Author(s):  
Makoto Ueno ◽  
Chigusa Morizane ◽  
Takuji Okusaka ◽  
Gakuto Ogawa ◽  
Yuya Sato ◽  
...  
Keyword(s):  
Renal Function ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Tract Cancer ◽  
Grade 3 ◽  
The Impact

368 Background: JCOG1113 is a randomized phase III trial to evaluate gemcitabine (GEM) plus S-1 (GS) versus GEM plus cisplatin (GC) regarding overall survival (OS) for advanced biliary tract cancer (BTC) (UMIN000001685) and the non-inferiority of GS was demonstrated. It is necessary to consider renal function using cisplatin or S-1 because cisplatin has renal toxicity, and the toxicity of S-1 is affected by renal function. Therefore, we evaluated the influence of renal function on the efficacy and safety of GC and GS in JCOG1113. Methods: All enrolled patients (pts) in JCOG1113 (n = 354) were analyzed. Eligibility criteria included chemotherapy-naïve pts with recurrent or unresectable biliary tract adenocarcinoma, ECOG-PS of 0–1, CCr > 50 ml/min, and adequate organ function. Renal function was classified into two groups by creatinine clearance (CCr) as calculated by the Cockcroft-Gault formula; high CCr (CCr ≥ 80 ml/min) or low CCr (80 > CCr ≥ 50 ml/min). The impact of renal function on OS and progression-free survival (PFS) were compared using the Cox regression model. The adverse events (AEs) were compared using Fisher’s exact test. Results: Eighty-eight pts on GC and 88 pts on GS were included in the high CCr group, and 87 pts on GC and 91 pts on GS were included in the low CCr group. There were no differences between the groups regarding, sex, PS, primary site, biliary drainage, operation, or recurrence, except for age. The hazard ratio (HR) of GS to GC for OS was 1.12 (95% CI 0.81–1.56) in the high CCr group and 0.80 (95% CI 0.58–1.11) in the low CCr group. The HR of GS to GC for PFS was 1.06 (95% CI 0.78–1.44) in the high CCr group and 0.69 (95% CI 0.50–0.94) in the low CCr group. Grade 3-4 AEs of white blood cell count decreased (35.3%/23.6%), anemia (29.4%/7.9%) and platelet count decreased (18.8%/10.1%) were more common in GC than GS in the low CCr group. In contrast, the incidence of all grade 3-4 non-hematological AEs was higher (36.0%/11.8%) in GS than GC in the low CCr group ( p = 0.0002). Conclusions: GS was better in terms of OS, PFS, and hematological toxicities than GC in the low CCr group. GS might be recommended for the population with lower renal function in the treatment for advanced BTC.

Phase III study of gemcitabine/oxaliplatin (GEMOX) with or without erlotinib in unresectable, metastatic biliary tract carcinoma.

2011 ◽  
Vol 29 (18_suppl) ◽  
pp. LBA4032-LBA4032 ◽  
Author(s):  
H. Y. Lim ◽  
J. Lee ◽  
H. Chang ◽  
J. S. Kim ◽  
H. J. Choi ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Performance Status ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Ampulla Of Vater ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Standard Regimen ◽  
Tract Cancer ◽  
Significant Difference

LBA4032 Background: Currently, there is no standard regimen for palliative chemotherapy in metastatic, unresectable biliary tract cancer (BTC). A phase II trial of erlotinib monotherapy showed a promising anti-tumor activity in BTC with tolerable toxicity. Additionally, gemcitabine + erlotinib demonstrated superior efficacy when compared to gemcitabine alone in pancreatic cancer. Hence, we conducted a phase III trial to compare between GEMOX vs GEMOX+erlotinib (Tarceva [T]) (GEMOX/T) as first-line chemotherapy in unresectable, metastatic BTC. Methods: Eligible patients were as follows: histologically confirmed adenocarcinoma of biliary tract (CCC), ampulla of vater (AOV) or gall bladder (GB); unresectable or metastatic; ECOG performance status of 0~2; adequate marrow, hepatic, renal and cardiac functions; no prior chemotherapy. The primary endpoint was progression free survival (PFS). The study regimen was gemcitabine 1,000mg/m2, oxaliplatin 100mg/m2, erlotinib 100mg qd daily q 2 weeks. Results: From February 2009 to August 2010, 268 pts were randomized, 133 patients to GEMOX arm and 135 patients to GEMOX/T arm. Patient characteristics: median age 61 yrs (range 30-82); male (63.4%); CCC (n=180, 67.2%), GB (n=82, 30.6%), and AOV (n=6, 2.2%). With a median follow-up of 13.9 months (range, 6.7 – 25.0), median PFS was 5.8 months (95% CI, 4.6 - 7.0) in GEMOX/T arm and 4.2 months (95% CI, 2.7 - 5.7) in GEMOX arm (P=0.080). In subgroup analysis (CCC, n=180), however, median PFS was significantly longer in GEMOX/T arm (5.9 months) when compared with GEMOX arm (3.0 months, P=0.049). The overall response rate was significantly higher in the GEMOX/T arm when compared with GEMOX arm. There was no significant difference in overall survival between the two arms (GEMOX/T: 9.5 months, 95% CI, 7.6 – 11.4; GEMOX: 9.5 months, 95% CI, 7.5 – 11.5; P=0.611). The EGFR mutation testing results in correlation to responsiveness to erlotinib will be presented at the meeting. Conclusions: This phase III represents the first multicenter, randomized trial to compare GEMOX vs GEMOX/T in unresectable, metastatic BTC. Although PFS was not prolonged in GEMOX/T, there was a significant benefit in terms of PFS in GEMOX/T arm for CCC patients.

Neutrophil/lymphocyte ratio (NLR) may predict prognostic factor with gemcitabine/cisplatin/S-1 (GCS) for patients with advanced biliary tract cancer (MITSUBA /KHBO1401-1B).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15656-e15656
Author(s):  
Toru Otsuru ◽  
Tatsuya Ioka ◽  
Hiroaki Nagano ◽  
Etsuro Hatano ◽  
Hidetoshi Eguchi ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Roc Curves ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Tract Cancer

e15656 Background: There is little information available about prognostic markers of gemcitabine, cisplatin, and S-1 (GCS) in patients with advanced biliary tract cancer (aBTC). Neutrophil/lymphocyte ratio (NLR) in several cancers including aBTC was reported to be a prognostic and/or predictive factor associated with clinical outcomes. There are no data about relation between NLR and clinical outcome in patient with aBTC who underwent GCS. Methods: Baseline demographics and NLR at enrollment were retrospectively evaluated in 119 patients who received GCS treatment in MITSUBA / KHBO1401 randomized phase III trial, which showed significant superiority of GCS to GC. The clinical utility of the NLR was evaluated by receiver operating characteristic (ROC) curves, and the cutoff values for NLR were 3.7. We divided these patients based on estimated NLR, and evaluated the clinicopathological factors and survival in the two groups (NLR ≧ 3.7 or < 3.7). Results: 32 patients were in NLR ≧ 3.7group and 87 patients were in NLR < 3.7 group. The progression-free survival between two groups was not significantly different (p = 0.45). Although, the median overall survival (OS) of NLR ≧ 3.7 group was 10.4 months, while OS of NLR < 3.7 group was 18.5 months (HR 0.55, 95% confidential interval [CI] 0.36-0.87; p = 0.01).The ratio that was able to continue chemotherapy from initial administration six months later was 83.4%of NLR < 3.7 group, and 65.6% of NLR ≧ 3.7 group (p = 0.04). Conclusions: Our study confirmed that high NLR is associated with worse OS, and suggested it may be a predictive marker for GCS chemotherapy in patients with aBTC.

Cisplatin plus irinotecan versus cisplatin plus gemcitabine in the treatment of advanced or metastatic gallbladder or biliary tract cancer: Results of a randomized phase II trial (NCT01859728)– the Gambit trial.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 529-529
Author(s):  
Lucas Vieira dos Santos ◽  
Gustavo Sanches Faria Pinto ◽  
Mauricio Wagner Souto Ferraz ◽  
Arinilda Bragagnoli ◽  
Florinda Santos ◽  
...  
Keyword(s):  
Adverse Events ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Distant Metastases ◽  
Complete Response ◽  
Current Standard ◽  
Tract Cancer ◽  
To Receive

529 Background: The combination of gemcitabine-cisplatin (GC) is the current standard of care chemotherapy for metastatic/unresectable biliary tract cancer (BTC). However, the prognosis remains poor. This randomized trial aimed to evaluate the efficacy and safety of irinotecan plus cisplatin (IP) versus GC in advanced or metastatic BTC. Methods: Patients with biopsy-proven, chemo-naïve, unresectable or metastatic BTC, ECOG 0-2, measurable disease per RECIST 1.1, adequate organ function and written informed consent were stratified by ECOG (0 or 1 vs 2) and distant metastases and randomized to receive irinotecan 65 mg/m² IV D1 and D8 plus cisplatin 60 mg/m² D1 repeated every 3 weeks (IP) or gemcitabine 1000 mg/m² IV D1 and D8 plus cisplatin 25 mg/m² IV D1 and D8 repeated every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results: Between January 2013 and April 2018, 47 pts were randomized (1:1) to receive IP (N = 24) or GC (N = 23). Overall, groups were well balanced according to prognostic factors. The ORR was 35% (complete response 5%, partial response 30%) and 31.8% in IP and GC arms, respectively. Median progression-free survival were 5.3 vs 7.8 months (HR = 1.165, 95%CI 0.628-2.161, p = 0.628) and median overall survival were 11.9 and 9.8 months (HR = 0.859, 95%CI 0.431 – 1.710, p = 0.665) for IP and GC, respectively. Adverse events were not statistically different between arms, and results were consistent with previous experiences with these regimens. No therapy-related death were reported. Conclusions: Irinotecan-cisplatin combination is active in BTC, with similar ORR, PFS and OS when compared to gemcitabine-cisplatin. Irinotecan-cisplatin were well tolerated, and adverse events were manageable. Irinotecan-cisplatin could be considered as an alternative to gemcitabine-cisplatin. Clinical trial information: NCT01859728.

Phase II trial of trifluridine/tipiracil and irinotecan for the treatment of advanced refractory biliary tract cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS594-TPS594
Author(s):  
Hao Xie ◽  
Mitesh J. Borad ◽  
Daniel H. Ahn ◽  
Tanios S. Bekaii-Saab ◽  
Nguyen H. Tran ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Rational Approach ◽  
Free Survival ◽  
Tract Cancer ◽  
Oncology Research

TPS594 Background: Effective treatment options are very limited for patients with advanced refractory biliary tract cancer (BTC). Fluoropyrimidine-based chemotherapy regimen such as 5-fluorouracil and irinotecan are frequently utilized for these patients after first-line therapy despite lack of FDA approval. Trifluridine/tipiracil (FTD/TPI) is a novel oral nucleoside with antitumor activity in both fluoropyrimidine sensitive and resistant tumors due to its unique mechanisms of action. Given early toxicity and efficacy data from our previous study on single-agent trifluridine/tipiracil (FTD/TPI) in advanced BTC, the clinical evaluation of its combination with irinotecan represents a rational approach for the treatment of advanced refractory BTC. Methods: This is a single-arm phase II trial with a two-stage design to assess the efficacy of trifluridine/tipiracil (FTD/TPI) and irinotecan in advanced refractory BTC. Key eligibility criteria include histologically confirmed advanced, unresectable BTC who have progressed on at least one line of systemic therapy and have measurable disease per RECIST v1.1. Target accrual is 25. Treatment includes trifluridine/tipiracil (FTD/TPI) 25 mg/m2 on days 1-5 and irinotecan 180 mg/m2 on day 1 in 14-day cycles. Patients will be evaluated for response every 4 cycles and in the absence of disease progression, therapy may be given up to 2 years. The primary end point is the progression-free survival rate at 16 weeks. Secondary endpoints include overall response rate, disease control rate, progression-free survival, overall survival, and incidence of adverse events. Correlative biomarker studies include evaluations of circulating tumor DNA and circulating tumor cells at baseline, after 4 cycles and at progression; and development of patient-derived tumor organoids from pre-treatment biopsies for parallel treatments. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc. Clinical trial information: NCT 04072445.

A phase II trial of trastuzumab plus modified-FOLFOX for gemcitabine/cisplatin refractory HER2-positive biliary tract cancer (BTC): Multi-institutional study of the Korean Cancer Study Group (KCSG-HB19-14).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4161-TPS4161
Author(s):  
Choong-kun Lee ◽  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Min Hwan Kim ◽  
Jin Won Kim ◽  
...  
Keyword(s):  
South Korea ◽  
Biliary Tract ◽  
Phase Ii ◽  
Biliary Tract Cancer ◽  
Objective Response ◽  
Phase Iii ◽  
Gene Copy ◽  
Her2 Positive ◽  
Extrahepatic Cholangiocarcinoma ◽  
Tract Cancer

TPS4161 Background: Biliary tract cancer (BTC), one of the most fatal cancers with limited treatment options, is generally rare in most high-income countries, but is relatively prevalent in South Korea. Recent genomic profilings have provided druggable molecular targets including HER2 amplification, which accounts for about 15% of total BTC patients. Trastuzumab is a humanized monoclonal antibody against HER2 with known efficacy in patients with HER2-positive breast and gastric cancer, and has not been tested prospectively in patients with HER2-positive BTC. The modified-FOLFOX regimen is currently being tested as a second-line therapy of BTC in phase III ABC-06 trial. This phase II study is investigating the combination of trastuzumab and modified-FOLFOX as second- or third-line treatment in HER2-postivie BTC. Methods: This study (KCSG-HB19-14; NCT04722133) is a phase II, multi-institutional, single arm trial to evaluate the efficacy and safety of trastuzumab plus modified-FOLFOX in gemcitabine/cisplatin refractory patients with HER2-positive BTC. The main inclusion criteria are HER2-positive (defined as IHC3+, or IHC2+/ISH+; ISH+ defined as HER2/CEP17 ≥2.0, or ERBB2 gene copy number ≥ 6.0 by NGS) BTC (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of vater cancer) patients who progressed on gemcitabine/cisplatin containing chemotherapy (one or two previous cytotoxic chemotherapy lines permitted), ECOG 0 or 1, and adequate organ function. Patients receive trastuzumab-pkrb 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m2 D1, leucovorin 200mg/m2 D1, 5-FU 400mg/m2 bolus D1, and 5-FU 2400mg/m2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression. The study has a Simon's two-stage design, with objective response rate (ORR) per RECIST v1.1 as primary endpoint. Secondary endpoints included progression-free survival, disease control rate, overall survival, safety, quality of life and correlative biomarker exploration. Additional patients were to be recruited if pre-specified thresholds for ORR are met at the first stage. The study will enroll up to 34 patients and is currently recruiting at eight sites in South Korea. As of February 2021, 16 patients have been enrolled. The pre-specified activity goal for the first stage of accrual was met; second stage accrual began in February 2021. Clinical trial information: NCT04722133.

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