RECIST v1.1 and irRECIST outcomes in advanced HCC treated with pembrolizumab (pembro).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 528-528
Author(s):  
Julien Edeline ◽  
Mark Karwal ◽  
Andrew X. Zhu ◽  
Richard S. Finn ◽  
Stéphane Cattan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Tumor Growth ◽  
Toxicity Study ◽  
Small Samples ◽  
Advanced Hcc ◽  
Continue Therapy ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information ◽  
Similar Incidence

528 Background: IO can cause pseudoprogression (PP): apparent tumor growth followed by stability or favorable response. We assess PP in aHCC treated with pembro (KEYNOTE-224 [ph 2], NCT02702414; KEYNOTE-240 [ph 3], NCT02702401). Methods: aHCC pts with PD on/intolerance to sorafenib received pembro 200 mg IV Q3W until unacceptable toxicity, study withdrawal, 2 y of therapy, or RECIST v1.1 PD; if pt clinically stable at PD, physician could continue therapy and repeat scans to confirm PD per irRECIST. PP=RECIST v1.1 PD then irRECIST response other than PD. Data cutoff: Jan 02, 2019 (KEYNOTE-240); Feb 13, 2018 (KEYNOTE-224). Results: 245/382 pembro-treated pts had RECIST v1.1 PD: 138 irRECIST repeat scan; 105 PD; 33 (8.6%; 33/382) outcomes other than PD. Of 33 PP, 29 had SD, 3 PR, 1 CR (irRECIST; 29 had this at first irRECIST scan; 4 [2 SD, 2 PR] at subsequent scan). For initial RECIST v1.1 PD, 16/33 PP had PD at first postbaseline scan (pembro cycles 2-4); 17/33 PP had PD at pembro cycles 4-18. Median (range) time to RECIST v1.1 PD in the 33 PP was 80 (37-378) days. OS shown in Table. KEYNOTE-240 had 135 PBO-treated pts: 8 (5.9%) PP; small samples bar meaningful interpretation. Conclusions: PP in aHCC, per irRECIST, has a similar incidence to other cancers (eg, melanoma) and does not seem to correlate with OS. Data may help physicians assess when to continue pembro after PD. Clinical trial information: NCT02702414, NCT02702401. [Table: see text]

Impact of renal impairment on clinical outcomes in patients (pts) with locally advanced or metastatic (LA/M) urinary tract carcinoma (UTC) treated with atezolizumab (atezo): Analysis of the international SAUL study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5036-5036
Author(s):  
Margitta Retz ◽  
Florian Seseke ◽  
Giuseppe Luigi Banna ◽  
Ugo De Giorgi ◽  
Thomas Powles ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Impairment ◽  
Overall Response Rate ◽  
Response Rate ◽  
Locally Advanced ◽  
Exclusion Criteria ◽  
Secondary Endpoints ◽  
Post Hoc ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

5036 Background: Atezo, which targets PD-L1, is an approved therapy for LA/M urothelial carcinoma based on the IMvigor210 and IMvigor211 trials. The single-arm SAUL study (NCT02928406) showed consistent activity and safety in a broader population, including understudied scenarios, eg pts with renal impairment or other IMvigor211 exclusion criteria. Methods: Pts with LA/M UTC received atezo 1200 mg q3w until disease progression or unacceptable toxicity. The primary endpoint was safety; secondary endpoints included overall response rate (ORR) and overall survival (OS). Post hoc analyses explored outcomes in pts classified as: chemotherapy (CT) ineligible (calculated creatine clearance [CrCl] 15– < 30 mL/min); cisplatin ineligible and carboplatin eligible (CrCl 30– < 60 mL/min); or cisplatin eligible (CrCl ≥60 mL/min). Results: Of 1004 enrolled pts, 46 (5%) were classified as CT ineligible and 420 (42%) as cisplatin ineligible. Results are summarized below. Conclusions: These post hoc analyses suggest pts typically considered cisplatin or CT ineligible are candidates for atezo. Pts with renal impairment achieved similar ORR and DCR to pts with CrCl ≥60 mL/min, without increased toxicity. Imbalances in pt characteristics may explain numerical differences in OS. Clinical trial information: NCT02928406 . [Table: see text]

On the Mathematical Basis of Zelen’s Prerandomized Designs

1985 ◽  
Vol 24 (03) ◽  
pp. 120-130 ◽  
Author(s):  
E. Brunner ◽  
N. Neumann
Keyword(s):  
Clinical Trial ◽  
Normal Distribution ◽  
Random Variables ◽  
Small Samples ◽  
Selection Effects ◽  
Sample Sizes ◽  
Mathematical Basis ◽  
Additional Assumptions

SummaryThe mathematical basis of Zelen’s suggestion [4] of pre randomizing patients in a clinical trial and then asking them for their consent is investigated. The first problem is to estimate the therapy and selection effects. In the simple prerandomized design (PRD) this is possible without any problems. Similar observations have been made by Anbar [1] and McHugh [3]. However, for the double PRD additional assumptions are needed in order to render therapy and selection effects estimable. The second problem is to determine the distribution of the statistics. It has to be taken into consideration that the sample sizes are random variables in the PRDs. This is why the distribution of the statistics can only be determined asymptotically, even under the assumption of normal distribution. The behaviour of the statistics for small samples is investigated by means of simulations, where the statistics considered in the present paper are compared with the statistics suggested by Ihm [2]. It turns out that the statistics suggested in [2] may lead to anticonservative decisions, whereas the “canonical statistics” suggested by Zelen [4] and considered in the present paper keep the level quite well or may lead to slightly conservative decisions, if there are considerable selection effects.

scholarly journals WSRF-Based Modeling of Clinical Trial Information for Collaborative Cancer Research

2008 ◽  
Author(s):  
Tianyi Zang ◽  
Radu Calinescu ◽  
Steve Harris ◽  
Andrew Tsui ◽  
Marta Kwiatkowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Research ◽  
Clinical Trial Information

Impact of adding plinabulin to pegfilgrastim for the prevention of TAC chemotherapy (Chemo) induced neutropenia (CIN), on patient quality of life (QoL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e24031-e24031
Author(s):  
Ramon Mohanlal ◽  
Yvette Lelorier ◽  
Dominic Mitchell ◽  
Lan Huang ◽  
Douglas W. Blayney
Keyword(s):  
Clinical Trial ◽  
Energy Levels ◽  
Breast Cancer Patients ◽  
Emotional Wellbeing ◽  
Phase 3 ◽  
Tac Chemotherapy ◽  
Physical Wellbeing ◽  
The Impact ◽  
Clinical Trial Information

e24031 Background: Plinabulin is a novel non-G-CSF small molecule being developed for the prevention of chemotherapy in conjunction with pegfilgrastim and is administered via 30 min IV infusion, 30 min after chemo on Day (D) 1. The QoL was analyzed using the Functional Assessment of Cancer Therapy - General questionnaire (FACT-G) as part of a phase 3 (Ph3) clinical trial comparing pegfilgrastim alone versus pegfilgrastim and plinabulin for the prevention of neutropenia in newly diagnosed breast cancer patients being treated with Docetaxel (75 mg/m2), Doxorubicin (50 mg/m2), and Cyclophosphamide (500 mg/m2) (TAC) on D1 for four 21 D cycles and study treatment. Methods: The FACT-G was administered to patients in China and Ukraine using an ePRO app downloaded onto patients' phones as part of the Phase 3 PROTECTIVE-2 trial (NCT0329457) with TAC. Patients completed the FACT-G during each chemo cycle at D-1, D1, D8 and D15. Patients received reminders 1 hour before the required completion time and all entries were time stamped. The FACT-G measured the impact of cancer on four categories: Physical wellbeing, Social wellbeing, Emotional wellbeing and Functional wellbeing. Results: Compared to pegfilgrastim alone, patients on plinabulin + pegfilgrastim performed significantly better for Physical wellbeing on D8 and D15 of Cycle 2 (p < 0.0589 and p < 0.0039 respectively) and Cycle 3 (p < 0.0360 and p < 0.0343 respectively). Further analysis of the sub questions showed that both energy levels “I have a lack of energy” and pain”(I have pain” were significantly better for the plinabulin + pegfilgrastim combination versus pegfilgrastim alone (p < 0.0377 and p < 0.0420 respectively). Overall FACT-G completion compliance for the trial was 91%. Conclusions: The Physical wellbeing (in particular, pain and for energy levels) of patients receiving plinabulin in combination with pegfilgrastim for the prevention of TAC CIN, was significantly less impacted by chemo dosing compared to the pegfilgrastim alone arm. In addition, the results suggest that patients receiving the combination therapy recovered their pre-chemo Physical wellbeing levels more rapidly. Clinical trial information: NCT03531099.

Analysis and Reporting Windows for Clinical Trial Information

1991 ◽  
Vol 25 (2) ◽  
pp. 289-294 ◽  
Author(s):  
Jack Faricelli ◽  
Gregory L. Lazarev
Keyword(s):  
Clinical Trial ◽  
Clinical Trial Information

Plain language summary of the CROWN study comparing lorlatinib with crizotinib for people with untreated non-small cell lung cancer

2021 ◽  
Author(s):  
Benjamin J Solomon ◽  
Todd M Bauer ◽  
Filippo de Marinis ◽  
Enriqueta Felip ◽  
Yasushi Goto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Side Effects ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Research Study ◽  
Small Cell ◽  
Plain Language ◽  
Small Cell Lung

This is a summary of a research study (known as a clinical trial) called CROWN. The study tested two medicines called lorlatinib and crizotinib in participants with untreated non-small cell lung cancer that had spread to other parts of their body. All those who took part had changes in a gene called ALK, which is involved in cell growth. In total, 296 participants from 23 countries took part. Half the participants took lorlatinib and half took crizotinib. After participants started taking lorlatinib or crizotinib, they were checked regularly to see if their tumors had grown or spread to other parts of their body (known as tumor progression) and to monitor any side effects. After 1 year of treatment, the participants who took lorlatinib were twice as likely to be alive with no tumor growth as the participants who took crizotinib. More participants who took lorlatinib had cancer that shrank (76%) compared with the participants who took crizotinib (58%). This was also true of the participants whose cancer had spread to their brain. The most common side effects in participants who took lorlatinib were increases in the amount of cholesterol and triglycerides (a type of fat) in their blood, swelling, weight gain, nerve damage, unclear thoughts, and diarrhea. Among the participants who took crizotinib, the most common side effects were diarrhea, feeling like you want to throw up, sight problems, swelling, vomiting, changes in liver function, and feeling tired. Overall, the CROWN study showed that fewer participants with advanced ALK+ non-small cell lung cancer died or had tumor growth with lorlatinib compared with crizotinib treatment. ClinicalTrials.gov NCT number: NCT03052608 .

A phase 2 trial of apatinib combined with intensity modulated radiation therapy for patients with unresectable hepatocelluar carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16136-e16136
Author(s):  
Shaobo Ke ◽  
Hu Qiu ◽  
Jin Peng ◽  
Gaoke Cai ◽  
Yutian Zhangcai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Performance Status ◽  
Objective Response ◽  
Intensity Modulated Radiation Therapy ◽  
Phase 2 ◽  
Hepatocelluar Carcinoma ◽  
Advanced Hcc ◽  
Intensity Modulated

e16136 Background: To estimate the clinical outcomes and safety for patients with unresectable advanced hepatocelluar carcinoma (HCC) treated with apatinib in combination with intensity modulated radiation therapy (IMRT). Methods: This study was an open-label, single-arm, phase 2 clinical trial of apatinib combined with IMRT for treatment of patients with unresectable advanced HCC. Patients aged between 18 and 75 years with adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between March 2017 and September 2020. Patients received IMRT (biologically effective dose(BED): 46-60Gy), and continuous apatinib (250-500 mg/d) orally until disease progression or unacceptable toxic effects. The primary end point was progression-free survival(PFS), the secondary end points included overall survival(OS), disease control rate (DCR), objective response rate(ORR) and safety. The data were analyzed for this report with cutoff on February 1, 2021. Results: A total of 46 patients were screened and 33 were enrolled in this study. The cohort had a median age of 56.7 years (range 21-77), 28(84.85%) were men. 25(75.76%) patients had hepatitis B, 32(96.7%) were BCLC stage B-C, 31(93.9%) were Child-Pugh A-B，and 8(24.2%) had portal vein involvement. Receiving first-line and second- or later-line treatment were 21(63.6%) and 12(36.4%), respectively. At a median follow-up of 11.6 months, the median PFS was 7.68 months(95% confidence interval:5.39-9.76) .The 6-month and 12-month overall survival rates were 100% and 96.2%, respectively. According to Response Evaluation Criteria in Solid Tumors Version 1.1, the ORR and DCR were 15% and 82%, respectively. There were 15 (15.2%) grade 3-4 treatment-related adverse events including neutropenia, thrombocytopenia, hypertension, proteinuria and hand and foot syndrome. There were no treatment-related deaths. Conclusions: Apatinib in combination with IMRT was safe and effective in improving PFS and DCR, and suggested an encouraging anti-tumor activity in patients with unresectable advanced HCC. Clinical trial information: ChiCTR-OPC-17011890.

Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16117-e16117
Author(s):  
Jian-Xu Li ◽  
Ting-Shi Su ◽  
Xiao-Feng Lin ◽  
Yi-Tian Chen ◽  
Shi-Xiong Liang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trial ◽  
Radiation Therapy ◽  
Clinical Study ◽  
Cancer Staging ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Open Label ◽  
Grade 3 ◽  
Clinical Trial Information

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

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