Preliminary results of a phase II trial of FOLFOX4 regimen in Chinese patients with unresectable primary liver cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14065-14065 ◽  
Author(s):  
S. K. Qin ◽  
Y. J. Wang ◽  
Q. Wu ◽  
B. C. Xing
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Phase Ii ◽  
Primary Liver Cancer ◽  
Safety Data ◽  
Median Number ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Open Label ◽  
Number Of Cycles

14065 Background: Primary liver cancer (PLC) is the 3rd most common cancer in whole China. Development of systemic chemotherapy for the patients not eligible for operation as well as TACE commonly have been required. Oxalipaltin (Eloxatin)+ 5-FU/LV, namely FOLFOX 4 regimen was tried to investigate its efficacy and safety in inoperable PLC. Methods: It was an open-label, single arm and multi-center phase II study to explore RR, DCR,TTP and MST. All the pts had pathologically confirmed inoperable PLC with/without distant metastasis. The pts were treated with the standard FOLFOX 4 regimen, that is OXA 85mg/m2 d1; LV 200mg/m2 IV 2hrs d1,2; 5-FU 400mg/m2 bolus, d1,2 and 5-FU 600mg/m2 CIV 22hrs d1,2; q2w upto 6 cycles or until progression. Tumor evaluation was done every 6 weeks using RECIST criteria. Neurotoxicity was evaluated by Eloxatin specific neurotoxicity criteria (Sanofi-Aventis Co.Ltd) and other toxicities by the NCI CTC AE version 2.0. Results: From July 2004 to Sep. 2005, 27 pts (21 male, 6 female) were recruited from the 4 cancer centers with average age of 56 ±13 years old. 25 patients (92.6%) had hepatocellular carcinoma, and 2 (7.4%) cholangiocellular carcinoma. 15 pts (55.6%) had metastatic disease. 1 pt received liver transplantation before inclusion. The median number of cycles was 4 per pt. 26 pts were evaluable for efficacy and safety. The RR was 19.2% (5/26; 1 CR and 4 PR), and DCR 57.7% (15/26; including 10 SD). 4 of the 5 responsive pts had hepatocellular carcinoma, and 1 had cholangiocarcinoma. Serum AFP level was significantly decreased (mean 131,890.4ug/dl at the baseline and 1,298.6ug/dl after 6 cycles) for the first 16 pts. The first 16 pts’ safety data were available in detail: 11 NCI grade 3/4 events were observed from a total of 76 cycles administered: including 5 neutropenia, 3 leucopenia, 1 thrombocytopenia, 1 infection and 1 liver dysfunction. Grade II & III neurotoxicity was found in 3 & 2 patients respectively. The TTP,MST and further safety data were under follow-up. Conclusions: The preliminary data of the FOLFOX 4 regimen for the advanced Chinese pts with inoperable PLC have shown encouraging results with the better efficacy and favorable safety profile. Further exploration in this area is warranted, especially in hepatocellular carcinoma. No significant financial relationships to disclose.

scholarly journals 452 Preliminary analysis of a real-world study (RWS) of camrelizumab treatment in primary liver cancer (PLC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A479-A480
Author(s):  
Zhendong Chen ◽  
Nianfei Wang ◽  
Dayong Luo ◽  
Bo Jiang ◽  
Mu Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Group Performance ◽  
Primary Liver Cancer ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Patient Disposition ◽  
Ecog Ps

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the landscape of PLC management at all evolutionary stages.1 As an anti-programmed cell death-1 (PD-1) antibody, camrelizumab monotherapy and in combination with apatinib, an anti-angiogenetic tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2, chemotherapy or locoregional therapy, have demonstrated their efficacy in advanced hepatocellular carcinoma (HCC).2 3 4 5MethodsThis prospective, open-label, multi-center, observational RWS was conducted to evaluate efficacy and safety of camrelizumab in treatment of PLC in clinical practice. Eligible patients were histopathologically or cytologically identified HCC or intrahepatic cholangiocarcinoma, who were going to receive camrelizumab treatment, with age ≥18 ages, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–2 and Child-Pugh score ≤ 9. Patients were treated at clinician discretion. Three hundred patients were planned to enroll, including advanced or peri-operative PLC. The primary endpoint was progress-free survival for advanced PLC, whose efficacy was available to analysis. Efficacy was assessed per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom March 29, 2020 to June 10, 2021,a total of 147 eligible patients of advanced PLC were enrolled and included in this interim analysis, with 128 (87.1%) men, 130 (94.9%) ECOG PS of 0–1, 139 (94.6%) HCC, 74 (50.4%) Barcelona Clinic Liver Cancer stage C, 98 (66.7%) Child-Pugh B, and 72 (49.0%) with extrahepatic metastases, shown in table 1. Of the 147 patients, 45 (30.1%) patients were treated with camrelizumab monotherapy, 79 (53.8%) patients with combination with angiogenesis inhibitors, of which 55 (37.4%) in combination with apatinib, 21 (14.3%) patients with camrelizumab and chemotherapy. Patients, who had at least one efficacy assessment, were included in the efficacy analyses. Up to July 19, 2021, with a median follow time of 6.2 months, 132 patients were available for efficacy analyses. Patient disposition was shown in figure 1. Objective response rate (ORR) and disease control rate (DCR) were 10%/30.8%/35.3% and 75.0%/86.5%/70.6% in camrelizumab monotherapy/combined with apatinib/combined with chemotherapy, respectively. (table 2) The most common camrelizumab-treatment related adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (12, 8.2%), ICI-induced pneumonia (2, 1.4%), enterocolitis (2, 1.4%), and nephritis (1, 0.7%), of which all these AEs recovered. Other AEs included increase of transaminase (5, 3.4%) and hypertension (4, 2.7%). All AEs were 1–2 grade and no treatment-related death occurred.Abstract 452 Table 1Baseline characteristicsAbstract 452 Figure 1Patient dispositionAbstract 452 Table 2Confirmed tumor response assessed by investigators per RECIST v1.1ConclusionsCamrelizumab, combined with anti-angiogenetic agents or chemotherapy, or monotherapy, demonstrated good efficacy and safety in treatment of PLC.Trial RegistrationChiCTR2000034264ReferencesLlovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7(1):6–28.Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21(4):571–580.Xu J, Shen J, Gu S, et al. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res 2021;27(4):1003–1011.Mei K, Qin S, Chen Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer 2021;9(3).Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31(28):3501–3508.Ethics ApprovalThis study was approved by China registered clinical trial ethics review committee with No.ChiECRCT20200042.

Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6058-6058 ◽  
Author(s):  
G. Nagaiah ◽  
P. Fu ◽  
J. K. Wasman ◽  
M. M. Cooney ◽  
C. Mooney ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Median Duration ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Median Number ◽  
Anaplastic Carcinoma ◽  
Open Label ◽  
Open Label Phase ◽  
Number Of Cycles

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]

scholarly journals Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial

2021 ◽  
pp. JCO.21.00163
Author(s):  
Shukui Qin ◽  
Feng Bi ◽  
Shanzhi Gu ◽  
Yuxian Bai ◽  
Zhendong Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Objective Response ◽  
Chinese Patients ◽  
First Line ◽  
Open Label ◽  
Multikinase Inhibitor ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Intention To Treat

PURPOSE Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months ( P = .0570). The objective response rate was 4.6% v 2.7% ( P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

2021 ◽  
Author(s):  
Yongkun Sun ◽  
Aiping Zhou ◽  
Wen Zhang ◽  
Zhichao Jiang ◽  
Bo Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

Abstract Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12mg/day, Day1–14, three weeks per cycle). The primary endpoint was 12-week progression free survival (PFS) rate. Relationship between series plasma cytokine level and efficacy of anlotinib was analyzed.Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% (95% confidence interval [CI]; 59.8%–91.5%) and median time to progression (TTP) was 5.9 months (95% CI; 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI; 48.7%–86.6%) and 4.6 months (95% CI; 2.7–10.0), respectively. The median TTP on patients with baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significant longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for efficacy of anlotinib.

A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Follicular Lymphoma (FL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2479-2479 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Alessandro Pulsoni ◽  
Manuela Balocco ◽  
Monica Tani ◽  
Stefano Fanti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Safety Data ◽  
Stage Iv ◽  
Bone Marrow Examination ◽  
Stage Ii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Open Label ◽  
Grade 3

Abstract We conducted a prospective, multicenter, single-arm, open-label, non-randomized, phase II study to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a new approach combining induction chemotherapy with oral Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated FL. Patient eligibility was represented by: age ≥ 18 years with biopsy-proven, untreated; stage II – IV FL grade I–II; WHO performance status of 0 to 2. All patients signed a written informed consent. Patients were treated with standard FM chemotherapy (Fludarabine was administered orally at the dose 40 mg/m2/day for 3 consecutive days) every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM. Patients achieving at least a PR after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was > 1500/μL, the platelet count >100.000/μL, lymphocytes expressing the CD20 antigen and the bone marrow examination at the completion of FM demonstrated < 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 62 patients were enrolled and 41 were evaluable for response. Of these 41 patients, all are evaluable for induction FM regimen and 19 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. 15 were male and 26 female; the median age was 52.5 years (range 36–70); 5 were stage II, 12 stage III, and 24 stage IV. After the FM treatment the OR rate was 100%, including 73% complete remissions (CR + CRu) and 27% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 20 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 19 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 3/5 (60%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 12 patients. These preliminary data indicate: 1) FM regimen including oral fludarabine presents the same activity of i.v. formulation one without significant gastrointestinal toxicity and with a better patient compliance; 2) feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for untreated FL. Final efficacy and safety data will be presented.

Efficacy and safety of nivolumab (NIVO) in patients with advanced melanoma (MEL) and poor prognostic factors who progressed on or after ipilimumab (IPI): Results from a phase II study (CheckMate 172).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9524-9524 ◽  
Author(s):  
Dirk Schadendorf ◽  
Paolo Antonio Ascierto ◽  
John B. A. G. Haanen ◽  
Enrique Espinosa ◽  
Lev V. Demidov ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Objective Response ◽  
Safety Data ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label

9524 Background: In the phase III CheckMate 037 study, NIVO improved the objective response rate and progression-free survival with less toxicity vs chemotherapy in patients (pts) with MEL who progressed after prior IPI treatment. We report the first efficacy and updated safety data from pts with MEL in CheckMate 172, including those with rare melanoma subtypes (uveal, mucosal), brain metastases, or an ECOG performance status (PS) of 2. Methods: In this ongoing phase II, single-arm, open-label, multicenter study, pts with MEL who progressed on or after IPI were treated with NIVO 3 mg/kg Q2W for up to 2 years until progression or unacceptable toxicity (NCT02156804). We report efficacy and updated safety data from 734 treated pts with ≥1 year of follow-up (database lock: November 2016). Results: Of 734 pts, 50% had LDH>ULN, 7% ECOG PS 2, 66% M1c disease, 15% a history of brain metastases, and 23% received ≥3 prior therapies. Overall, 593 pts (81%) received more than 4 doses of NIVO. Overall, response rate at 12 weeks was 32%, with a complete response in 1% (Table). The 1-year overall survival (OS) rate was 63%. Any grade and grade 3/4 treatment-related adverse events (AEs) occurred in 66% and 17% of pts, respectively. Discontinuations due to treatment-related AEs occurred in 4% of pts. The most common treatment-related select (potentially immune-related) AEs were diarrhea (12%), hypothyroidism (9%), and pruritus (7%). Conclusions: CheckMate 172 is the largest study of NIVO efficacy and safety in pts with MEL who progressed on or after IPI. NIVO demonstrated a safety profile consistent with that of prior clinical trials. Efficacy outcomes were encouraging in some difficult-to-treat subgroups of pts with poor prognostic factors, such as mucosal melanoma and brain metastases. Clinical trial information: NCT02156804. [Table: see text]

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