Phase II trial of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma (HCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 240-240 ◽  
Author(s):  
Aiwu Ruth He ◽  
Anteneh Tesfaye ◽  
Daniel Smith ◽  
John Marshall ◽  
Michael J. Pishvaian ◽  
...  
Keyword(s):  
Dna Repair ◽  
Disease Progression ◽  
Cancer Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Common Grade ◽  
Grade 3

240 Background: The combination of the imidazotetrazine derivative temozolomide (TMZ) and poly(ADP-ribose) polymerase inhibitor veliparib (ABT-888) has shown in vivo activity against a variety of tumor types through the alkylating effects of TMZ and DNA repair inhibition by ABT-888. To date, no studies have examined the combination of TMZ and ABT-888 in treating advanced HCC refractory to sorafenib. Methods: This is a single arm Phase II trial. Eligible HCC patients have Child Pugh A/B cirrhosis and have failed prior treatment with sorafenib either through intolerance or disease progression. All patients have received ABT-888 40 mg daily on days 1-7 and Temozolomide 150 mg/m2 daily on days 1-5 in 28 day cycles for a maximum of 6 cycles. Tumor response is analyzed every 2 cycles using RECIST criteria. The primary endpoint is time to disease progression. The trial is being conducted using a modified Simon’s two-stage design optimal design as implemented by Hanfelt, et al. Results: The trial is currently in Simon Stage 1 with 16 patients recruited: 9 patients have stopped the study due to disease progression, 3 patients are still on protocol, and 4 patients stopped the study for reasons other than disease progression. 7 patients had disease progression at two months, 1 patient had cancer progression at 4 months, and 1 patient had disease progression at 16 months. Median time to progression in these 9 patients was 56 days (range 42-486 days). The four patients that stopped the study prematurely were for the following reasons: hiccups/dehydration, Mallory-Weiss tear secondary to refractory nausea, intraperitoneal bleeding from exophytic HCC lesion, and development of hepatorenal syndrome in a paracentesis-dependent patient. The most common grade 3 toxicities in this cohort so far have been nausea/vomiting (in 2 subjects), and anemia/thrombocytopenia (in 2 subjects). Defects in DNA repair pathways are being tested from the liver biopsy in the patient who had response to TMZ and ABT-888 for 16 months. Conclusions: The combination of TMZ and ABT-888 is fairly tolerated in patients with advanced HCC. So far, the treatment did not show activities in majority of patients with advanced HCC. Clinical trial information: NCT01205828.

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.

A phase II trial of temsirolimus (TEM) and bevacizumab (BEV) in patients with advanced hepatocellular carcinoma (HCC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4099-4099 ◽  
Author(s):  
Jennifer J. Knox ◽  
Rui Qin ◽  
Jonathan R. Strosberg ◽  
Andreas Kaubisch ◽  
Anthony B. El-Khoueiry ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Vegf Inhibitor ◽  
Common Grade ◽  
Prior Systemic Therapy ◽  
Grade 3 ◽  
Stage 1

4099 Background: There is strong rationale to combine an m-TOR inhibitor (TEM) with a VEGF inhibitor (BEV) as a potentially active and well tolerated treatment for HCC. Both agents have shown modest single agent activity in HCC and so evaluated here in a phase II trial. Methods: A modified 2-stage Simon design planned 25 or 50 patients (pts) to test the null hypothesis that true tumor response rate is at most 10% andtrue 6-mo progression-free survival rate (PFS) (by RECIST) is at most 65%, or no better than single agent BEV (6 mo PR >2 pts or PFS 6 mo >18 out of 25.) Toxicity, TTP, PFS and survival were 2nd endpoints. Eligible pts had confirmed HCC with disease unresectable or amenable to other localised therapies, Child Pugh A liver status and no prior systemic therapy involving the VEGF or m-TOR class of agents. TEM was administered at starting dose 25 mg IV d1,8,15,22 with BEV at 10mg/kg IV d 1, 15, all q 28 days (1 cycle). Imaging was q 8 wks. Results: From 09/09 to 09/11, 27 eligible pts were enrolled with 25 evaluable for toxicity and efficacy. Med age 59 yrs, 85% male, PS 0/1: 35/65, 58% metastatic, >85% BCLC stage C. With med 6 cycles (range 1-14) delivered, most pts (88%) experienced a grade 3+ adverse event (a/e.) Common grade 3 a/es related to treatment included thrombocytopenia (40%), neutropenia (20%), leucopenia (12%), fatigue (8%), anemia, mucositis, dyspnea, diarrhea, bleeds, fistula, infections (4% each). There was one possible treatment related death. Per protocol dose reductions/discontinuation for TEM-related a/es were most common. There were 2 confirmed PRs and 16 pts progression-free by 6 mos. A third pt developed a late PR at cycle 13. Median TTP on study was 6 mos, median PFS was 7.4 mos and median survival was 8.3 mos, with 13 pts still alive. Accrual closed at end of stage 1 as neither the number of responses nor the PFS at 6 mos passed the futility stopping rule set for this combination. Conclusions: This multicenter study is the first HCC trial evaluating the BEV/TEM doublet. Despite manageable toxicity, the ORR and 6 mo PFS did not surpass assumptions based on single agent BEV in HCC. Further study of BEV/TEM combination in this advanced HCC population is not recommended.

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.

Phase II trial of pazopanib in progressive, metastatic, iodine-insensitive differentiated thyroid cancers

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3521-3521 ◽  
Author(s):  
K. C. Bible ◽  
R. C. Smallridge ◽  
W. J. Maples ◽  
J. R. Molina ◽  
M. E. Menefee ◽  
...  
Keyword(s):  
Disease Progression ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Measurement Data ◽  
Colon Perforation ◽  
Clinical Activity ◽  
Thyroid Cancers ◽  
Grade 3 ◽  
Differentiated Thyroid Cancers

3521 Background: Systemic therapies have had little impact on the outcomes of patients with advanced differentiated thyroid cancers. Methods: A three-outcome one-stage Phase II trial was conducted to assess the anti-tumor activity and toxicities of the orally bioavailable VEGF/tyrosine kinase inhibitor pazopanib (800 mg daily) in patients with advanced and progressive radioiodine-insensitive differentiated thyroid cancers. Up to 2 prior therapies were allowed, with measurable disease required. Design: at the 0.10 significance level, there would be a 90% chance of detecting a RECIST response rate of >20% given a true response rate of >5%; with the regimen considered promising if >4 confirmed responses observed. Results: From February to November 2008, 32 patients (53% male) aged 23–79 years (median: 63 years) were enrolled. Common sites of metastases were: lung (100%), nodes (52%), and bone (39%). Measurement data are available for 26 patients, with the median number of cycles administered thus far 4 (range: 1–8, total: 101). Overall, therapy has been well tolerated. Six patients (23%) required dose reduction due to: grade 2+ ALT (3 pts), grade 3 mucositis (1 pt); grade 3 diarrhea and dehydration (1 pt), and grade 3 abdominal pain (1 pt.). Other serious toxicities included grade 3 colon perforation and grade 3 chest pain (1 pt). No thyroglobulin antibody (TGA) negative patient has become TGA positive, and 11 of 16 patients (69%) with initially elevated thyroglobulin levels experienced a decline in thyroglobulin of >50%. Five RECIST partial responses have been confirmed to date (19%). Two patients are alive with disease progression and another has died from disease progression. Conclusions: Pazopanib appears to have both a favorable toxicity profile and promising clinical activity in patients with advanced and progressive differentiated thyroid cancers. Supported in part by NCI CA15083 and CM62205. No significant financial relationships to disclose.

Clinical, pharmacodynamic (PD), and pharmacokinetic (PK) evaluation of cediranib in advanced hepatocellular carcinoma (HCC): A phase II study (CTEP 7147).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4112-4112 ◽  
Author(s):  
Andrew X. Zhu ◽  
Marek Ancukiewicz ◽  
Jeffrey G. Supko ◽  
Lawrence Scott Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Steady State ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Eligibility Criteria ◽  
Advanced Hcc ◽  
Baseline Levels ◽  
Grade 3

4112 Background: Sorafenib remains the only approved systemic therapy in HCC. We performed a phase II study of cediranib (AZD2171)—a more potent and selective pan-VEGF receptor inhibitor—in advanced HCC patients (pts). Methods: Eligibility criteria included unresectable or metastatic measurable HCC, ECOG PS ≤2, CLIP score ≤3, and adequate organ function. Patients received cediranib at 30 mg po qd continuously (4-wk cycle). The primary endpoint was progression free survival (PFS). We also assessed overall survival (OS) and response rates, steady-state PK of cediranib, and blood circulating biomarkers. Results: Since 6/16/09, we have enrolled the targeted 17 pts required for the first stage of the planned study: ECOG 0/1/2=5/11/1, CLIP 1/2/3=6/4/7, Child A/B=14/3, BCLC C=17. Nine pts had prior sorafenib. The best response was stable disease in five pts (29%). The median PFS was 5.3 months (95% CI: 3.5-9.7). The median OS was 11.7 months (95% CI: 7.5-13.6). Grade 3 toxicities included hypertension (29%), hyponatremia (12%), elevated SGOT (12%) and one pt each (6%) in SGPT, fatigue, hyperbilirubinemia, cardiac ischemia, and proteinuria. Grade 4 pulmonary embolism and brainstem hemorrhage occurred in 1 pt each. Steady-state PK parameters (mean±SD) were, Cmin, 22±21 ng/mL; Cmax, 55±33 ng/mL; AUCτ, 887±503 ng*h/mL. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2 and Ang-2 decreased significantly after cediranib treatment (p<0.05). PFS was inversely correlated with baseline levels of bFGF, sVEGFR2 and VEGF, and OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-alpha and CD34+CD133+ hematopoietic progenitor cells (p<0.05). Conclusions: Cediranib at 30 mg daily is associated with high frequency of grade 3 hypertension and shows preliminary evidence of antitumor activity in advanced HCC pts. Exploratory studies confirmed potential PD and response biomarkers of anti-VEGF therapy. Cediranib exhibits similar PK in HCC pts as in those with other tumor types and normal/near normal hepatic function. This study was stopped by AstraZeneca after discontinuation of cediranib development for unrelated factors.

EVOLVE-1: Phase 3 study of everolimus for advanced HCC that progressed during or after sorafenib.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 172-172 ◽  
Author(s):  
Andrew X. Zhu ◽  
Masatoshi Kudo ◽  
Eric Assenat ◽  
Stéphane Cattan ◽  
Yoon-Koo Kang ◽  
...  
Keyword(s):  
Disease Progression ◽  
Treatment Options ◽  
Study Drug ◽  
Final Analysis ◽  
Best Supportive Care ◽  
Hbv Reactivation ◽  
Advanced Hcc ◽  
Common Grade ◽  
Load Increase ◽  
Grade 3

172 Background: No effective treatment options exist for advanced HCC following sorafenib failure. Preliminary data suggest everolimus may provide benefit after sorafenib. EVOLVE-1 (NCT01035229) assessed the efficacy and safety of everolimus for advanced HCC after sorafenib failure. Methods: Pts aged ≥18 y with BCLC stage B or C HCC and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were sorafenib intolerant were randomized 2:1 to everolimus 7.5 mg/d or placebo. All pts received best supportive care. Randomization was stratified by region (Asia v rest of world) and macrovascular invasion (yes v no). Study drug was given continuously until disease progression or intolerable toxicity. CT/MRI was performed every 6 wk. Primary endpoint was OS. Secondary endpoints were TTP, disease control rate (DCR; percentage of pts with best overall response of CR, PR, or SD per RECIST 1.0), and safety. Final analysis was performed when 454 deaths occurred. Results: 546 pts from 18 countries enrolled from Apr 2010 to Mar 2012 (everolimus = 362, placebo = 184). Baseline characteristics were balanced between arms; median age was 66.0 y, 84.8% of pts were male, 86.3% had BCLC stage C disease, 16.7% were from Asia, 32.8% had macrovascular invasion, and 74.0% had extrahepatic disease. Prior sorafenib was discontinued for disease progression in 80.8% of pts and intolerance in 19.0%. Median OS was 7.56 mo with everolimus and 7.33 mo with placebo (HR 1.05; 95% CI 0.86-1.27; P = .675). Median TTP was 2.96 mo and 2.60 mo, respectively (HR 0.93; 95% CI 0.75-1.15). DCR was 56.1% and 45.1%, respectively (P = .010). The most common grade 3/4 AEs with everolimus (v placebo) were anemia (7.8% v 3.3%), asthenia (7.8% v 5.5%), decreased appetite (6.1% v 0.5%), and hepatitis B viral load increase or reappearance (6.1% v 4.4%). No pts experienced HCV flare. HBV reactivation was experienced by 39 pts (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy. Conclusions: Everolimus did not improve OS in pts with advanced HCC whose disease progressed on or after sorafenib or who were sorafenib intolerant. The safety profile was consistent with that previously observed with everolimus. Clinical trial information: NCT01035229.

A phase II trial of 5-weekly S-1 plus cisplatin (CDDP) combination with trastuzumab (Tmab) for HER2-positive advanced gastric or esophagogastric junction (EGJ) cancer: WJOG7212G (T-SPACE) study.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Yuji Miura ◽  
Toshimi Takano ◽  
Yasutaka Sukawa ◽  
Katsuhiko Nosho ◽  
Shuichi Hironaka ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Weekly Schedule ◽  
Her2 Positive ◽  
Primary Tumor Site ◽  
Common Grade ◽  
Accrual Rate ◽  
First Results ◽  
Grade 3

126 Background: Five-weekly schedule of S-1 plus CDDP (5-weekly SP) is the standard first-line chemotherapy for the patients (pts) with advanced gastric cancer (AGC) in Japan. Tmab with fluoropyrimidine plus CDDP chemotherapy has shown a survival benefit for pts with HER2-positive AGC and EGJ cancer. However, little information on the efficacy and safety of 5-weekly SP combined with Tmab is available. Methods: We conducted a prospective, single arm, multicenter, phase II trial of 5-weekly SP (S-1 40-60 mg bid for 21 days plus CDDP 60 mg/m2on day 8, every 5 weeks) combined with Tmab (8 mg/kg as a loading dose then 6 mg/kg, every 3 weeks) for pts with HER2-positive (IHC 3+ or IHC 2+ and FISH positive) AGC or EGJ cancer. Primary endpoint was response rate (RR) evaluated by independent review committee, using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. With power of 80% and one-sided alpha of 10%, thirty-five pts were required to reject 40% of RR under expected 60% RR. During the study, protocol was amended based on the favorable accrual rate. Pts were enrolled over 35 to improve precision, until pts enrollment up to 55 (power 85% and alpha 5%) or the end of predetermined accrual period, whichever came first. Results: Between August 2012 to January 2014, 44 pts were enrolled. Pts’ characteristics were: males 34 (77%), median age 62.6 years, PS 0-1 42 (95%), primary tumor site of stomach 37 (84%), histology of diffuse type 18 (41%). IHC 3+ was recorded in 32 (73%) pts. The RR was 64% (95% CI 48-78, one-sided p<0.001). The median PFS was 6.0 months (95% CI 5.1-10.9). The median OS was not reached. The toxicities in the first four courses were assessed. The most common grade 3 to 4 adverse events were anorexia (23%), diarrhea (11%), neutropenia (23%), anemia (16%), and thrombocytopenia (11%). One (2%) treatment-related death was reported. Conclusions: 5-weekly SP combined with Tmab showed a good efficacy with acceptable toxicities for pts with advanced AGC or EGJ cancer. Clinical trial information: UMIN000008389.

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 CTNI-47. PHASE II STUDY OF ABEMACICLIB IN RECURRENT GBM PATIENTS WITH CDKN2A/B LOSS AND INTACT RB

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii53-ii53
Author(s):  
Eudocia Lee ◽  
Alona Muzikansky ◽  
Isabel Arrillaga-Romany ◽  
Ugonma Chukwueke ◽  
Timothy Cloughesy ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Recurrent Glioblastoma ◽  
Open Label ◽  
Cyclin Dependent Kinases ◽  
Best Response ◽  
Common Grade ◽  
First Relapse ◽  
Grade 3 ◽  
Recurrent Gbm

Abstract Deregulation of the cyclin-dependent kinases (CDK) 4 and 6 (cdk4/6)–cyclin D-INK4—retinoblastoma protein (Rb) signaling pathway is among the most common aberrations found in glioblastoma (GBM) with more than 80% of patients estimated to be affected. We conducted an open label, multi-center, phase II trial of abemaciclib in participants with recurrent glioblastoma (GBM) at their first relapse and with documented evidence of CDKN2A/B loss and intact RB from archival tissue. A total of 32 patients enrolled on the non-surgical arm of the study with 13 women (40.63%) and median KPS 90 [range 60–100]. The PFS6 rate was 9.37% [95% CI, 2.4%, 22.27%], median PFS 55 days [95% CI, 49, 56], and median OS 384 days [95% CI, 228, 488]. Out of 31 evaluable patients, best response was PR 1 (3.2%), SD 11 (35.5%), and PD 19 (61.3%). The most common grade 3 or higher toxicities at least possibly related to abemaciclib included leukopenia (21.9%), neutropenia (18.6%), lymphopenia (9.4%), and thrombocytopenia (6.3%). Abemaciclib has minimal activity in this preselected recurrent GBM population. Correlative studies from the surgical arm of this study are pending.

Sorafenib plus cisplatin and gemcitabine in the treatment of advanced hepatocellular carcinoma (HCC): A phase II study by the Gruppo Oncologico dell'Italia Meridionale (prot. GOIM 2705).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 225-225 ◽  
Author(s):  
F. Giuliani ◽  
A. Febbraro ◽  
R. Addeo ◽  
D. Rizzi ◽  
E. Maiello ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Treatment ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Hepatic Function ◽  
Tumor Control ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Advanced Hcc ◽  
Written Informed Consent

225 Background: Sorafenib is the standard treatment in advanced HCC. The combination of cisplatin and gemcitabine demonstrated to be active and well tolerated in tumors with a similar poor outcome such as pancreatic and biliary-tract cancers. Considering these data, the GOIM started a phase II trial aiming to evaluate the activity and safety of the combination of sorafenib, gemcitabine and cisplatin in advanced HCC. Methods: Patients affected by advanced HCC, not suitable for surgery or locoregional procedures, with measurable disease (Recist criteria), age ≥ 18 years, clip-score ≤3, ECOG performance status ≥ 60 (K.fsky), adequate bone marrow reserve and renal and hepatic function and who signed written informed consent, were enrolled and received cisplatin 40 mg/mq iv plus gemcitabine 800 mg/mq iv bi-weekly, while sorafenib was orally administrated at the dosage of 400 mg bid continuously. A maximum of 6 cycles of chemotherapy was planned; a maintenance with sorafenib was permitted for not progressing patients. The evaluation of activity was performed every three cycles. A Simon's two stage, two steps study design was applied: at the first step, at least 3 OR had to be observed among the first 28 patients to continue the enrollment. Up to now, 23 patients have been enrolled. Their main characteristics were: sex (male/female) 19/4, median age: 70 yrs, median PS 80,main sites of disease liver 22, lymph nodes 4, lung 2, others 3. Results: Up to now 18 patients are evaluable for activity while 5 are too early. One CR, 3 PR, 6 SD and 8 PRO for an ORR of 4/18 (22%) and a tumor control of 10/18 (55%). Twenty-one patients are evaluable for safety. The main observed side effects (%G1-2/G3-4) (NCI criteria) were: hand-foot skin reaction (HFSR) 9/14, mucositis 9/4, diarrhea 23/4, nausea/vomiting 23/0, leucopenia 23/0, anemia 9/0, thrombocytopenia 19/4, asthenia 14/14, cardiovascular 0/4, others 9/4. Conclusions: Our preliminary data seems to demonstrate that the combination of cisplatin, gemcitabine, and sorafenib is active and well tolerated in advanced HCC patients. The accrual is ongoing. No significant financial relationships to disclose.

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