bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of changes in chest wall mechanics in esophageal cancer survivors using a 3D-motion capture system.
Authors: Tukanova Karina , Banger Matthew , Hanna George , McGregor Alison , Markar Sheraz 
Published: January 2022

TPS360 Background: Surgical resection remains the mainstay of treatment for loco-regional esophageal cancer. Traditional open esophagectomy is associated with considerable morbidity, with postoperative pulmonary complications (PPC) being the most frequently observed morbidity. There are several peri- and postoperative factors that are known to affect the respiratory mechanics, including an open surgical approach, administration of sedatives, rib spreading with subsequent fracture or nerve injury, presence of PPC and neuropathic pain leading to post-thoracotomy syndrome. Enhanced recovery programmes with early mobilization protocols and chest physiotherapy have been shown to reduce pulmonary complication rates. However, no data is currently available regarding the long-term respiratory function, quality of life and chest wall function in esophageal cancer survivors. Quantification of chest wall movements provides an objective measurement of function for the long term assessment of chest wall mechanics and could be used to develop tailored physiotherapy for patients undergoing esophagectomy. The aim of this study is to develop a method to objectively quantify changes in breathing mechanics in esophageal cancer survivors using a biomechanical approach. Methods: In the initial phase, an 89-marker protocol will be validated against a 3D-printed chest wall model that can produced simulate of normal and abnormal motions. Retroreflective markers will be placed non-invasively on the anterior, posterior, and lateral parts of the thorax and abdomen. A working protocol of breathing mechanics will be assessed in healthy control volunteers with the subject seated in upright position. Subjects will perform the respiratory function tests, the spirometer and the respiratory pressure meter. Further to this clinical assessment, the impact of thoracic movements and treadmill exercise will be assessed on the parameters obtained from changes in breathing movements. Following this, an optimization phase will refine markers placement and identify parameters that are most likely to be clinically relevant in the assessment of breathing mechanics. A finalized protocol will be trialled in esophageal cancer survivors, to identify changes in thoracoabdominal motion after surgery and to assess whether these changes are associated with impairment in health-related quality of life. This information will aid the development of evidenced based physiotherapy regimens tailored to the needs of this patient population. Clinical trial information: NCT03835273.
A prospective, multicenter, dose-escalation, and dose-expansion study evaluating apatinib plus chemotherapy in second-line therapy of patients with postoperatively gastric cancer (ACHIEVE).
Authors: Han Junyi , Pang Tao , Zhang Zhan , Lu Zhengmao , Dong Ping , Wu Jianguo , Yin Kai , Chang Xusheng , Luo Tianhang 
Published: January 2022

TPS362 Background: Apatinib, a highly selective small-molecule tyrosinase inhibitor of VEGFR2, is the third-line standard therapy for patients (pts) with advanced gastric cancer. Many previous studies have preliminarily demonstrated the efficacy and safety of apatinib combined with chemotherapy in the second-line treatment of gastric cancer. Comparing with pts who have not undergone surgery, previous pharmacological study has found that pts who have undergone gastric cancer surgery have lower bioavailability and can tolerate higher doses of apatinib (Clin Pharmacokinet. 2017 Jan; 56(1):65-76). However, there is no prospective evidence of apatinib plus chemotherapy for second line treatment in pts with postoperatively gastric cancer. Methods: To explore the efficacy, safety and the maximum tolerated dose (MTD) of apatinib from apatinib+chemotherapy for second line treatment in pts with postoperatively gastric cancer. We designed ACHIEVE as a multicenter, dose-escalation, and dose-expansion trial in pts with gastric or gastroesophageal junction cancer who had prior undergone gastrectomy. In part 1 (dose escalation), pts who had received previously first-line treatment will be assigned to 1 of 3 three dose groups: (1) apatinib (250mg qd) + chemotherapy drug; (2) apatinib (500mg qd) + chemotherapy drug; (3) apatinib (750mg qd) + chemotherapy drug. The therapeutic drugs for second-line chemotherapy are determined by the investigator, it’s recommended to use docetaxel or albumin-bound paclitaxel, and chemotherapeutics are used for up to 6 cycles. In part 2 (dose expansion), pts will be treated with apatinib (MTD determined by dose escalation, qd) + chemotherapy drug. Whether PD-1 or PD-L1 inhibitors have been used in the first-line treatment will be analyzed as a subgroup analysis factor. Primary endpoints are progression-free survival (PFS) and MTD. Secondary endpoints include confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), and safety. AEs will be monitored throughout the study and graded per NCI CTCAE v5.0. Tumor response will be assessed by RECIST v1.1 every 6 weeks in the first 18 weeks, and every 9 weeks thereafter. Clinical trial information: ChiCTR2100048288.
INTEGRATE IIb: A randomized phase III open label study of regorafenib + nivolumab versus standard chemotherapy in refractory advanced gastroesophageal cancer (AGOC).
Authors: Pavlakis Nick , Shitara Kohei , Sjoquist Katrin Marie , Martin Andrew James , Jaworski Anthony , Yip Sonia , Oh Do-Youn , Moehler Markus H. , Bekaii-Saab Tanios S. , Simes John , Goldstein David 
Published: January 2022

TPS366 Background: Advanced Gastro-oesophageal Carcinoma (AGOC) has a poor prognosis, and there is no established standard treatment following failure of first- and second-line chemotherapy. Regorafenib (BAY 73-4506) is an investigational oral multi-targeted tyrosine kinase inhibitor (TKI) which targets angiogenic (VEGF, TIE-2), stromal (PDGF-β), and oncogenic (RAF, RET and KIT) receptor tyrosine kinases, and has shown activity in this setting. Single agent regorafenib prolonged progression free survival (PFS) versus placebo across all regions/subgroups in the INTEGRATE randomised phase 2 trial. Current options in refractory AOGC involves sequencing through chemotherapy with the latest active agent approved being trifluridine/tipiracil, TAS-102. Promising activity in refractory AOGC has been seen with the combination of regorafenib & nivolumab. INTEGRATE IIb–will compare the effectiveness of the combination of regorafenib & nivolumab in pre-treated patients with AGOC to current standard chemotherapy. Methods: Randomised phase III, open label study with 2:1 randomisation (RegoNivo : standard chemotherapy) and stratification by: Geographic region (Asia vs. Rest of World); Prior VEGF inhibitors (Yes vs No); Prior immunotherapy (Yes vs No). RegoNivo arm will receive 90mg (3x30mg) of regorafenib days 1-21 of each 28-day treatment cycle with intravenous nivolumab 240 mg day 1 of each 14 day cycle until disease progression or prohibitive adverse events as per protocol. The control arm will receive the investigator’s choice of the following chemotherapy; a taxane (paclitaxel or docetaxel), irinotecan or oral trifluridine/tipiracil (TAS102). Primary endpoint: OS. Secondary endpoints: PFS, response rate, quality of life, toxicity, exploratory correlative biomarkers. Clinical trial information: NCT04879368.
SGNTUC-019: Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations—Biliary tract cancer cohort.
Authors: Bekaii-Saab Tanios S. , Ramos Jorge , Tan Qianwen , Nakamura Yoshiaki 
Published: January 2022

TPS489 Background: Tucatinib (TUC), a highly selective HER2-directed TKI approved in multiple regions for HER2+ metastatic breast cancer, is being investigated as a novel therapy for patients (pts) with metastatic colorectal cancer, gastric cancer, and other GI tumors. Preclinical and clinical data have shown HER2-targeted agents may improve clinical outcomes. In xenograft models of HER2+ and HER2-mutated tumors, dual targeting of HER2 with TUC + trastuzumab (Tras) showed superior activity to either agent alone (Kulukian 2020). Interim results from the MOUNTAINEER study have shown promising activity for TUC + Tras in HER2+ colorectal cancer. In 23 response-evaluable pts, an objective response rate (ORR) of 52% was observed with a median progression-free survival (PFS) of 8.1 months (mo) (Strickler 2019). The prognosis for pts with biliary tract cancers (BTCs) remain poor, and treatment options are limited. Given that approximately 12%-15% of BTC pts are HER2+, and 1%-8% have HER2 mutations, TUC + Tras warrants further evaluation in this patient population. The SGNTUC-019 basket study (NCT04579380) is evaluating TUC + Tras in pts with previously treated, locally advanced, unresectable or metastatic solid tumors including BTC that display HER2 overexpression/amplification or activating mutations. We describe the design of the BTC cohort. Methods: SGNTUC-019 is a multi-cohort, open-label, international Phase 2 study. Pts must be ≥18 years old; have an ECOG PS of ≤1; have adequate hepatic, hematological, renal, and cardiac functions; and have no previous exposure to HER2-directed therapy. BTC pts must have progressed on or after ≥1 previous line of treatment. The HER2+ BTC cohort will enroll 12 response-evaluable pts. If >2 responses are observed, the cohort will be expanded to 30 pts. HER2-mutated BTC patients may also be enrolled in a 30 pts cohort for other HER2-mutated solid tumors. The primary objective is antitumor activity with confirmed ORR as the primary endpoint. Secondary efficacy endpoints include disease control rate, duration of response, PFS, and OS. For eligibility, HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH, or by HER2 amplification/mutation in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. Pts will receive TUC 300 mg orally twice a day and Tras 8 mg/kg intravenously on Cycle 1 Day 1 then 6 mg/kg every 21 days from Cycle 2 Day 1. Disease assessments per RECIST 1.1 are every 6 weeks for the first 24 weeks, then every 12 weeks. Quality of life will be evaluated every 2 cycles using EQ-5D-5L. Sites are currently enrolling within the US, EU and Asia-Pacific. Clinical trial information: NCT04579380.
Bridge-to-transplant stereotactic body radiation therapy in patients with hepatocellular carcinoma and advanced cirrhosis.
Authors: Hissourou Mohammad , Farsad Khashayar , Enestvedt C. Kristian , Fung Alice , Schlansky Barry , Naugler Willscott E , Nabavizadeh Nima 
Published: January 2022

TPS496 Background: Liver cancer is the third most common cause of cancer related death worldwide, and hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancers, with pre-existing cirrhosis being a very strong risk factor for HCC development. Liver transplantation (LTx) is the best treatment for patients with HCC and advanced cirrhosis as both conditions can be very effectively treated at once. As LTx wait-lists can be many months, liver-directed therapies (LDT), including stereotactic body radiation therapy (SBRT) to one or few lesions are essential as oncologic temporizing measures to bridge patients to LTx and prevent progression outside of LTx criteria. However, due to the fear of further hepatic decompensation, many patients with advanced cirrhosis are excluded from receiving LDT. Rather, recent studies suggest that SBRT be of safe and practical use in this fragile patient population with advanced cirrhosis and HCC, and thereby reduce the rate of transplantation drop-out. This pilot prospective study will assess the feasibility, safety and efficacy of bridge-to-transplantation SBRT for patients with advanced cirrhosis and HCC. Methods: Patients with non-metastatic and unresectable HCC and Child-Pugh (CP)-B8 or worse cirrhosis who are within Milan criteria (one tumor ≤ 5 cm in diameter or no more than 3 tumors each ≤ 3 cm in diameter) and have been listed or recommended to be listed for liver transplantation will be eligible for participation. Eligible participants will undergo SBRT consisting of 40 Gy to be given in 5 fractions every other day to the only or largest lesion, provided that criteria for normal organ constraints are met. In cases where normal organ constraints are not met, the dose will be iteratively de-escalated to two dose levels (35 Gy in 5 fractions, then 30 Gy in 5 fractions). If normal organ constraints are unable to be met at 30 Gy in 5 fractions, the participant will be considered ineligible for SBRT and considered a screen failure. The primary endpoint is the proportion of participants who are transplanted or with localized disease control that meets Milan criteria within a year of SBRT. Secondary endpoints will include localized control rate (mRECIST), incidence of intra- or extra-hepatic progressive disease (mRECIST), overall survival, incidence of liver toxicity per CTCAE v5.0, incidence of non-classical radiation-induced liver disease (defined as CTCAE grade 4 AST/ALT elevation or an increase in CP score of ≥ 2 within 3 months of SBRT) and quality of life scores per QLQ-C30 and FACT-Hep questionnaires. The study is open, aiming to enroll 15 patients with 8 patients enrolled at time of submission. Clinical trial information: NCT03812289.
Comparing the outcome of doublet therapy (gemcitabine and cisplatin) with triplet therapy (gemcitabine, cisplatin and nab paclitaxel) in locally advanced or metastatic gall bladder carcinoma patients: An open-label randomized control trial.
Authors: Khatri Chandrani , Das Pratap K. , Patowary Jayanta 
Published: January 2022

TPS497 Background: There are various studies evaluating the role of dual agent chemotherapy like gemcitabine and cisplatin in locally advanced or metastatic gall bladder cancer (1). This has been the standard of treatment up till now. Also there has been a single arm phase II trial of gemcitabine, cisplatin and nab-paclitaxel (triplet therapy) by Shroff et al (2) reporting an impressive data with RR (response rate) of 45 %, median PFS (progression free survival) of 11.8 months (5% CI; 6.0-15.6) and median OS (overall survival) was 19.2 months. This data was promising when compared to historical data of dual agents like gemcitabine and cisplatin. So it would be informative to conduct an RCT comparing doublet chemotherapy in locally advanced or metastatic GBC with triplet regimen chemotherapy. Methods: It is an open label randomized control study conducted in Indraprastha Apollo hospital New Delhi, India in newly diagnosed locally advanced or metastatic gall bladder cancer patients proven histologically and on imaging. The sample size calculated using the appropriate formula is, 27 in each arm that is total of 54 patients, but 60 patients will be enrolled in the study keeping in view 10% drop out rate. For simple randomization, we will use online computer generated random number table and then patients will be assigned in two groups, arms A and B. Arm A receiving two drugs gemcitabine 1,000mg/m2 i.v and cisplatin 25mg/m2 i.v on Day 1 and Day 8 of 21-day cycle and arm B receiving three drugs gemcitabine, 1,000 mg/m2, cisplatin, 25 mg/m2, and nab-paclitaxel, 125 mg/m2, on days 1 and 8 of 21-day cycle. Primary end point was response rates based on radiological response as per RECIST or PRECIST. Secondary end points were to determine median progression free survival and median overall survival and to evaluate the toxicities according to NCI-CTC v 4.0.Then response [on basis of RECIST or PRECIST criteria] will be seen after 3 and 6 cycles of chemotherapy are completed and at follow up of every 6 months for 2 years period for assessment of primary and secondary end points of the study. Statistical analysis for correlation between clinical and laboratory features and treatment outcomes will be done using the SPSS software. Till now we have enrolled 1 patient in each arm. CTRI/2021/09/036362. References: Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-81. Shroff RT, Javle MM, Xiao L, et al. Gemcitabine,Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial JAMA Oncol 2019. Clinical trial information: CTRI/2021/09/036362.
A phase 1b/2, open-label study of tivozanib in combination with durvalumab in subjects with advanced hepatocellular carcinoma (Deductive).
Authors: Dayyani Farshid , Lee Arielle Shebay , Li Daneng , Rowe Julie Haewon , Beg Muhammad Shaalan , Kasturi Vijay , Iyer Renuka V. 
Published: January 2022

TPS499 Background: 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 combination of atezolizumab and bevacizumab (which blocks VEGF-A ligand binding to VEGFR2) has improved the standard of care in advanced hepatocellular cancer with a median PFS of 6.8 months and 1-year overall survival of 67.2%. All the currently used agents in the second-line setting, have been evaluated in pts with HCC only after exposure to sorafenib. Treatment option for the patients with HCC that progress on atezolizumab and bevacizumab, are therefore limited. Methods: Deductive (NCT03970616) is a phase 2, multicenter, open-label study to assess the safety and efficacy of tivozanib in combination with durvalumab in patients with advanced HCC. Cohort A (n=20) includes patients with untreated advanced HCC. Cohort B (n=20) includes patients with advanced HCC who have progressed on/after treatment with prior bevacizumab and atezolizumab. Eligibility criteria include age >18 years, histologically or cytologically confirmed HCC, measurable or evaluable disease, Child-Pugh Class A, and ECOG PS of 0 or 1. Subjects will receive tivozanib 0.89 mg orally once daily for 21 consecutive days followed by 7 days off, and durvalumab 1500 mg intravenously every 4 weeks, and will be treated until progression or unacceptable toxicity. Study assessments include CT scan or MRI of the chest, abdomen, and pelvis every 8 weeks following Cycle 1 Day 1 until the end of treatment, and every 12 weeks during the first year and every 6 months thereafter until disease progression or start of another anti-cancer therapy. The primary objective is to establish the safety and tolerability of tivozanib in combination with durvalumab in subjects who are untreated (cohort A) or have been pre-treated with both bevacizumab and atezolizumab (cohort B). Secondary endpoints include estimation of objective response rate (ORR), median PFS and OS. Exploratory endpoints are to assess the durvalumab pharmacokinetics in the presence of tivozanib. Deductive is currently enrolling at 12 sites in the United States. Clinical trial information: NCT03970616.
HELIX-ICC: An-open label phase II trial of induction systemic mFOLFIRINOX followed by concurrent hepatic arterial infusion of floxuridine and systemic mFOLFIRI for unresectable intrahepatic cholangiocarcinoma.
Authors: Walker Brett S , Kardosh Adel , Eil Robert , Wong Melissa , Fung Alice , Brody Jonathan , Anand Sudarshan , Corless Christopher L. , Hansen Lissi , Rosenkranz Susan , Park Byung , Chen Emerson Yu-sheng , Jackson Anna , Vo Johnson , Fahlman Anne , Rocha Flavio G. , Lopez Charles D. , Goodyear Shaun , Mayo Skye C. 
Published: January 2022

TPS500 Background: The majority of patients with intrahepatic cholangiocarcinoma (ICC) present with advanced liver dominant disease rendering them unresectable. The current standard of care supports palliative treatment of unresectable ICC with gemcitabine plus cisplatin. Alternatively, continuous liver-directed therapy using a surgically implanted hepatic arterial infusion (HAI) pump allows for maximal treatment of liver tumors with limited systemic side-effects and can facilitate conversion to a resectable status. No prospective clinical trial has utilized FOLFIRINOX in combination with HAI floxuridine-dexamethasone for ICC. Methods: HELIX-ICC is a first-line, single-center, single-arm, phase II clinical trial enrolling patients with liver-dominant unresectable or multifocal ICC. Only patients with microsatellite stable cancer and no prior liver radiotherapy will be included. Patients are administered dose-modified FOLFIRINOX systemically for 4 cycles over 8 weeks. Those with evidence of disease control on restaging imaging and laparoscopy will proceed to HAI pump placement. Treatment continues with two 28-day cycles of combined HAI floxuridine (1.08 mg/kg) with dexamethasone for 14 days and systemic dose-modified FOLFIRI starting on day 15. The primary objectives are to evaluate the safety and efficacy (disease control rate [DCR] at 6 months) of this novel treatment approach that utilizes our institutional dose-reduced HAI floxuridine protocol in combination with modified systemic regimens to facilitate control of liver disease and maximize patient quality of life (QoL). HELIX-ICC includes many exploratory analyses through longitudinal collection of blood samples, liver biopsies (including an end of trial research biopsy), and QoL metrics (Table). The study is open to n = 30 with an initial safety run-in of 6 patients, of which 4 have enrolled at the time of submission. This study is designed to allow for drop out of 9 patients, with total accrual of 21 patients to protocol completion achieving 80.2% power at 0.05 significance to detect a 25% increase in DCR at 6 months. Clinical trial information: NCT04251715. [Table: see text]