Final phase Ib data for the oral c-Met inhibitor tepotinib in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15676-e15676 ◽  
Author(s):  
Sandrine J. Faivre ◽  
Jean-Frédéric Blanc ◽  
Philippe Merle ◽  
Angelica Fasolo ◽  
Angelo Iacobellis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Tumor Size ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Phase Ib ◽  
Advanced Hcc ◽  
Peripheral Edema ◽  
Met Inhibitor ◽  
Grade 3

e15676 Background: The prognosis for patients (pts) with advanced hepatocellular carcinoma (HCC) after failure of sorafenib is poor, with few systemic therapy options. c-Met is a receptor tyrosine kinase implicated in the progression of HCC. Tepotinib, a highly selective c-Met inhibitor, has shown activity first-line in patients with c-Met+ HCC. We report final results of a phase Ib study of tepotinib in pts with advanced HCC after failure of first-line sorafenib. Methods: Eligible pts were ≥18 years with advanced HCC, Child-Pugh Class A, ECOG PS 0-1, and progression after ≥4 weeks of sorafenib. Tepotinib doses of 300 and 500 mg/day on a 21-day cycle were explored to establish the recommended phase II dose (RP2D) of tepotinib. Secondary objectives included antitumor activity by RECIST v1.1, biochemical response, and safety. Results: Seventeen pts were enrolled: 4 pts received tepotinib 300 mg/day and 13 pts 500 mg/day, confirmed as the RP2D. Fourteen pts experienced treatment-related adverse events (TRAEs), the most frequent being peripheral edema (n = 5, 2 grade 3), lipase increase (2, 1 grade 3), acute kidney injury (2, 1 grade 3), renal impairment (2, 1 grade 3), fatigue (2), nausea (2), asthenia (2). One pt with peripheral edema permanently discontinued treatment. No grade ≥4 TRAEs and no dose-limiting toxicities (DLTs) were reported. The best overall response was partial response (PR) in 2 pts and stable disease (SD) in 4 pts. The duration of the PRs was 57 and 91 weeks. In the first of these pts, tumor size decreased by 55% and serum alfa-fetoprotein (AFP) levels had decreased from 15,923 μg/L at baseline to < 3,000 μg/L by day 15 of cycle 2 and remained at this level until progression. In the second pt, tumor size decreased by > 60% from baseline. No consistent change in AFP was seen in pts with SD. Median overall survival was 7.2 months (range 0.7–22.9 months). Conclusions: The RP2D of tepotinib as second-line therapy for pts with advanced HCC who progress after sorafenib treatment is 500 mg/day. Tepotinib was well tolerated at this dose and showed signs of activity. The ongoing phase II part of this trial is investigating the efficacy and safety of tepotinib 500 mg/day in pts with c-Met+ HCC. Clinical trial information: NCT02115373.

scholarly journals Gemcitabine Plus Carboplatin in Patients with Advanced Hepatocellular Carcinoma: Results of a Phase II Study

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Aly M. Azmy ◽  
Khalid E. Nasr ◽  
Nagy S. Gobran ◽  
M. Yassin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Stage ◽  
Survival Times ◽  
Advanced Hcc ◽  
Disease Stabilization ◽  
Grade 3

Objectives. Assessment of gemcitabine/carboplatin combination in patients with advanced-stage hepatocellular carcinoma (HCC) in a phase II trial for safety and efficacy. Methods. Forty patients with previously untreated advanced-stage HCC were prospectively enrolled and subjected to gemcitabine/carboplatin regimen which consisted of gemcitabine 1000 mg/m2 on days 1 and 8, and carboplatin AUC 6 on day 1. The treatment was repeated every 3 weeks until disease progression or limiting toxicity. Results. Forty patients were assessable for efficacy and toxicity. In all, 276 treatment cycles were administered. No toxic deaths occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%). Grade 3 carboplatin-induced neurotoxicity was observed in 3 (9%) patients. ORR was 23% (95% CI, 0.10–0.29) with 9 partial responses and disease stabilization was observed in 46% (95% CI, 0.22–0.42) of patients, giving a disease control rate of 69%. Median progression-free and overall survival times were, respectively, 5 months (95% CI: 3–8 months) and 8 months (95% CI: 6–18 months). Conclusion. The gemcitabine/carboplatin regimen seems to be effective, well tolerated, and active in advanced HCC.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

DEDUCTIVE: A study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma—Phase Ib results.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 294-294
Author(s):  
Renuka V. Iyer ◽  
Daneng Li ◽  
Farshid Dayyani ◽  
Alexandria T. Phan ◽  
Michael N. Needle ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Phase Ii ◽  
Single Agent ◽  
Objective Response ◽  
Primary Objective ◽  
Advanced Hepatocellular Carcinoma ◽  
Cross Sectional ◽  
Advanced Hcc ◽  
Grade 3 ◽  
Improve Patient

294 Background: A recent ph3 study combining bevacizumab (VEGF-A Mab) with atezolizumab (PD-L1 inhibitor) has shown significant improvements in OS and PFS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over sorafenib. Tivozanib (T, a potent and selective VEGFR 1, 2 & 3 TKI) and durvalumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies. T blocks all three VEGF receptors, and when combined with a PD-L1 inhibitor may improve patient outcomes. The ph1 portion of this study combines T with D to establish the recommended phase II dose (RP2D) and provide preliminary safety and efficacy data. Methods: Major eligibility criteria are adults with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance > 40 ml/min. Major exclusion criteria are co-infection with HBV and HCV and significant organ dysfunction. The starting dose is the combination of T 1 mg orally for 21 days followed by 7 days off treatment and D 1500 mg intravenously every 28 days. A DLT is generally defined as the occurrence of any Grade ≥3 immune or non-immune adverse event (AE) in Cycle 1 that is at least possibly related to the investigational regimen other than any grade of vitiligo or alopecia or Grade 3 controllable hypertension in cycle 1. The primary objective is to establish the RP2D and the safety and tolerability for this combination in patients with advanced HCC. Patients will be treated until progression of disease, unacceptable side effects, or death. Outcome measures will be AEs per CTCAE v.5 and cross-sectional imaging performed every 8 weeks. Results: Seven patients were enrolled in phase I. Six were male; the median age was 75 (range 40 to 82). One patient had mild elevation of LFTs and did not complete the 21-day course of T and was replaced. No patient experienced a >=grade 3 AE in cycle 1. The most common AEs, each seen in two of seven patients, were anorexia, cough, diarrhea, dysphonia, fatigue, hypertension, and palmar-plantar erythrodysesthesia. Two of seven have achieved a partial response. Conclusions: The combination of T with D in patients with untreated advanced HCC is well tolerated. The RP2D for the combination is T 1 mg orally for 21 days on treatment followed by 7 days off treatment and D 1500 mg intravenously every 28 days. In the phase II portion of the study an additional 30 patients will be treated at the RP2D. Secondary objectives are to assess the objective response rate, progression free survival, and overall survival in this population. Clinical trial information: NCT03970616.

scholarly journals Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 707 ◽  
Author(s):  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Vito Longo ◽  
Angela Calabrese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Prognostic Markers ◽  
Kinase Inhibitor ◽  
Quality Standard ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

scholarly journals Bevacizumab with Erlotinib as First-line Therapy in Asian Patients with Advanced Hepatocellular Carcinoma: A Multicenter Phase II Study

Oncology ◽  
2013 ◽  
Vol 85 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Chih-Hung Hsu ◽  
Yoon Koo Kang ◽  
Tsai-Shen Yang ◽  
Chia-Tung Shun ◽  
Yu-Yun Shao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
First Line Therapy ◽  
Asian Patients ◽  
Multicenter Phase ◽  
Line Therapy

Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
F. P. Costa ◽  
A. C. de Oliveira ◽  
R. Meirelles ◽  
M. M. Machado ◽  
R. Surjan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Electromagnetic Fields ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Advanced Hcc ◽  
Independent Review

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.

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