bluuebunny/crossref_metadata_2025_split huggingface dataset:
LENVAGIST - A multicenter, comparative, placebo-controlled, double-blinded, phase II study of the efficacy of lenvatinib in patients with locally advanced or metastatic GIST after failure of imatinib and sunitinib.
Authors: Le Cesne Axel , Cropet Claire , Gautier Julien , Gagne Stéphanie , Francourt Katia , Remir Emilie , Hernandez Caroline , Dufresne Armelle , Ray-Coquard Isabelle Laure , Carbonnaux Mélodie , Mery Benoite , Vanacker Helene , Bertucci Francois , Launay Simon , Louvel-Perrot Delphine , Monneur Audrey , Brahmi Mehdi , Blay Jean-Yves 
Published: May 2020

TPS11568 Background: GastroIntestinal Stromal Tumors (GIST) are paradigmatic models of cancers with a driver mutation of an oncogene, in which imatinib is recommended as adjuvant therapy or treatment of locally advanced and metastatic forms. After failure of imatinib (either progression or toxicity), sunitinib and regorafenib are indicated as 2nd and 3rd lines, respectively. Beyond approved drugs, tyrosine kinase inhibitors (TKI) can bring clinical benefit because some clones remain sensitive to TKI. Lenvatinib is a broad spectrum TKI targeting KIT, RET, PDGFRA, VEGFR 1-3 and FGFR 1-4, that is approved in the treatment of differentiated thyroid carcinoma and metastatic renal cell carcinoma and hepatocellular carcinoma. Methods: This prospective, randomized, placebo-controlled, double-blinded, multicenter trial evaluates the efficacy and safety of Lenvatinib in adult GIST patients (pts) who failed at least to previous imatinib and sunitinib. Seventy-four pts will be randomly allocated in a 1:1 ratio to receive either oral lenvatinib, at a daily dose of 24mg, or its matching placebo, continuously, until progression of disease (PD) or unacceptable toxicity. Randomization will be stratified according to the number of different previous anticancer drugs (2 or > 2). The primary objective is to compare the Progression-free survival (PFS) between arms. The expected median PFS are 1.5 month in the control arm and 3.0 months in the experimental arm (HR = 0.5). Seventy one events will provide 90% power to show significant improvement in PFS, using a 2-sided log-rank test at a 10% level. Secondary endpoints include the overall survival, the objective response rate, the best overall response, the quality of life and the safety profile. Patients allocated in the placebo arm who experience PD (RECIST 1.1) may switch to active lenvatinib. Radiological endpoints will be evaluated using the RECIST 1.1. Translational objectives will be to identify blood and tumor parameters as predictive markers of lenvatinib efficacy. Recruitment has been activated in January 2020. Ten participating sites of the French Sarcoma Group will participate in the trial. Clinical trial information: NCT04193553 .
The TNT protocol: A phase II study using talimogene laherparepvec (TVEC), nivolumab (N) and trabectedin (T) as first, second/third line therapy for advanced sarcoma, including desmoid tumor and chordoma.
Authors: Chawla Sant P. , Chua Victoria S. , Kim Katherine , Dy Paul Stendahl , Paz Micaela Kristina , Angel Nicole , Wang Kelly , Moradkhani Ania , Quon Doris , Wong Steven , Jafari Omid , Gordon Erlinda Maria 
Published: May 2020

TPS11572 Background: Talimogene laherparepvec (TVEC), an oncolytic HSV expressing huGMCSF, may be synergistic with trabectedin (T) and nivolumab (N) in treating advanced sarcoma. Objectives: (1) To evaluate the best overall response by RECIST v1.1, progression-free survival rate (PFS), and overall survival rate, (2) To determine the incidence of conversion of an unresectable tumor to a resectable one, and (3) To evaluate the incidence of adverse events related to the drug combination. Methods: This is an open label phase 2 study. A total of 40 patients will receive T (1.2 mg/m2 CIV over 24 hours q3 weeks), N (240 mg IV over 30 min q 2 weeks) and TVEC (intratumorally q 2 weeks according to tumor size). Eligible patients are those with histopathologically confirmed diagnosis of locally advanced, unresectable or metastatic sarcoma including desmoid tumor and chordoma, previously untreated or treated, with measurable disease by RECIST v1.1, and at least, one accessible tumor for intratumoral injection of TVEC. Currently, 31 of the 40 patients have been enrolled. Statistical Considerations: Continuous variables will be summarized by the sample size (n), mean, standard deviation, first and third quartiles, minimum and maximum. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Safety (incidence and severity of adverse events and significant laboratory abnormalities) will be performed on all patients (ITT population). Patient incidence of all treatment emergent AEs will be tabulated by system organ class and preferred term. Clinical trial information: 03886311 .
A phase Ib/III randomized, double-blind, placebo-controlled study of tazemetostat plus doxorubicin as frontline therapy for patients with advanced epithelioid sarcoma.
Authors: Sen Shiraj , McKean Meredith Ann , Sierra Laura , Ainscough Jessica , Yang Jay , Hamlett Anthony , Zimmerman Tom , Merchant Melinda , Chawla Sant P. 
Published: May 2020

TPS11573 Background: Epithelioid sarcoma (ES) is characterized by loss of inhibitor of integrase 1 (INI1), allowing enhancer of zeste homologue 2 (EZH2) to repress cell differentiation and promote tumorigenesis. Tazemetostat (TAZ) is an EZH2 inhibitor approved by the FDA as monotherapy for the treatment of patients (pts) aged ≥16 years with metastatic or locally advanced ES ineligible for complete resection. The most common ( > 20%) adverse events include pain, fatigue, nausea, decreased appetite, vomiting, and constipation. TAZ demonstrated anti-cancer activity in ES pts who previously received doxorubicin (dox), a commonly used front line FDA approved therapy for soft tissue sarcomas (STS), including ES. Preclinical studies have demonstrated synergy between TAZ and dox. This phase 1b/3 study (NCT04204941) is assessing the safety and efficacy of TAZ + dox in pts with advanced ES. Methods: This study is enrolling treatment-naïve adult pts with histologically confirmed STS (phase 1b) or INI1-deficient ES pts (phase 3) with ECOG performance status of 0-2 and life expectancy of ≥3 months. The open-label phase 1b portion is currently enrolling up to 24 patients with STS. The primary objectives are to evaluate the safety and tolerability of TAZ + dox, and to identify the recommended phase 3 dose (RP3D). Using a standard 3 + 3 design, TAZ will be evaluated at 3 dose levels (400 mg, 600 mg, and 800 mg orally BID) with standard fixed dose of dox (75 mg/m2 on day 1 of 21-day cycles for up to 6 cycles). After completion of dox, pts will continue to receive TAZ monotherapy until disease progression or intolerable toxicity. Up to 12 additional pts will be enrolled at the maximum tolerated dose for collection of additional safety and pharmacokinetic (PK) data. The double-blind phase 3 study will randomize (1:1) up to 140 pts to receive either TAZ (RP3D) + dox (75 mg/m2) or placebo + dox. The adaptive study design will allow sample size re-estimation (at interim analysis) to up to 200 pts. Pts may continue TAZ or placebo monotherapy after completing 6 cycles of TAZ + dox. Tumor assessments will be performed at screening and every 6 weeks from the start of dosing. The primary objective of phase 3 will be to evaluate the progression-free survival (PFS) by independent review committee. Secondary objectives will include assessment of PFS by investigators, overall survival, safety, disease control rate, overall response rate, duration of response, time to subsequent anticancer therapy, PFS on next treatment, quality of life, and PK. Clinical trial information: NCT04204941 .
An oro-buccal nanoparticle delivered cannabis medicine for pain management in cancer: A clinical trial in progress.
Authors: Clarke Stephen John , Vitetta Luis , McLachlan Andrew J , Henson Jeremy David , Rutolo David , Hall Sean 
Published: May 2020

TPS12127 Background: Cannabinoid molecules derived from Cannabis sativa L. have been posited to ameliorate conditions, including pain, chemotherapy induced nausea and multiple sclerosis associated spasticity. The clinical use of cannabinoids refers to a wide variety of formulations and extracts that may contain different active ingredients and adulterants as well as inter batch variability. Novel matrix formulations (e.g., water-soluble nanoparticles) for cannabis delivery may add further efficacy and tolerability to standard routes of administration (e.g., oral / gastrointestinal, inhaled, sublingual). This is further emphasized by the dysbiotic effects on the intestinal microbiome reported for oral formulations of medicinal cannabis, and which resulted in reduced efficacy. Similar results have been reported for other psychotropic compounds, such as alcohol and nicotine. Therapeutic use of cannabinoid formulations may be mode of delivery dependent in order to achieve safe, tolerable and effective doses. Methods: A water soluble oro-buccal nanoparticle spray with a racemic 1:1 mixture of Delta9Tetrahydrocannabinol (D9THC) and Cannabidiol (CBD), which bypasses the gastrointestinal system and first pass metabolism by accessing the systemic circulation via the facial lymphatics system, was investigated in patients with advanced cancer and unrelieved pain in a single ascending dose and multiple ascending dose in a first-in-human study. Results: The THC / CBD combination delivered as a submicron particle demonstrated safety, tolerability and a pharmacokinetic profile suitable for maintenance analgesic therapy. Preliminary analysis found an overall (n = 25) improvement in pain scores, especially in the subgroup of patients with bone metastases (n = 8), who obtained a greater than 30% average reduction in pain severity. 1 Clinical trial information: ACTRN12617001480370 .
A phase Ib study of the safety and pharmacology of nilotinib to prevent paclitaxel-induced peripheral neuropathy in patients with breast cancer.
Authors: Adams Elizabeth J. , Lustberg Maryam B. , Jin Yan , Li Yang , Sparreboom Alex , Hu Shuiying 
Published: May 2020

TPS12128 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating adverse effect of paclitaxel, but convincing evidence for a preventative technique founded on mechanistic rationale is lacking. We previously report that paclitaxel accumulation is mediated by the murine organic anion transporting polypeptide, OATP1B2 in mice (OATP1B1 and OATP1B3 in humans) (Leblanc, J Clin Invest, 2018). We found that paclitaxel induces acute and chronic neurotoxicity in mice in an OATP1B2-dependent manner, which is reversed by pre-treatment with FDA-approved tyrosine kinase inhibitor, nilotinib. Methods: This phase Ib dose finding study of nilotinib in combination with weekly paclitaxel is investigating the hypothesis that intermittent dosing of nilotinib 24 hours before paclitaxel infusion (excluding C1D1) and again 30 minutes before paclitaxel infusion will inhibit OATP1B1 and prevent CIPN. This hypothesis will be assessed using an adaptive Bayesian method for dose finding based on efficacy-toxicity trade-offs in patients with breast cancer stages I-III who qualify for paclitaxel therapy. Patients with previous ≥ grade 2 neuropathy on breast cancer therapies will be excluded. The primary objectives are to find the recommended phase II dose of nilotinib in combination with paclitaxel for early stage breast cancer, defined as the lowest intermittent dose of nilotinib that temporarily inhibits OATP1B1 function without affecting paclitaxel plasma pharmacokinetics (PK), and to determine the toxicity profile of nilotinib in combination with paclitaxel. OATP1B1 inhibition by nilotinib will be assessed via validated surrogate endogenous substrates, glycochenodeoxycholate sulfate (GCDGA-S) and chenodeoxycholate-24-glucuronide (CDCA-24G). Effective OATP1B1 inhibition will be ≥5-fold increase in AUC of GCDCA-S from pre- to post- treatment or detectable CDCA-24G levels post-treatment. The 4 nilotinib dose levels are 50 mg (dose level -1), 100 mg (dose level 1), 200 mg (dose level 2), 300 mg (dose level 3). IV paclitaxel dose of 80 mg/m2 on D1,8,15 for 12 total weekly doses will be used. Oral nilotinib will be administered 24 hours before paclitaxel infusion on C1D7,D14 and again 30 minutes before infusion on C1D8,D15. Secondary objectives are to determine paclitaxel’s effect on PK of nilotinib and vice versa. Quality of life via CIPN-20 survey, disease free survival, event free survival, overall survival are exploratory objectives. NCT04205903 enrollment opened February 2020 and is accepting patients. Clinical trial information: NCT04205903 .
Use of simulation for training family caregivers of patients receiving radiation therapy.
Authors: Mazanec Susan R , Blackstone Eric , Dorth Jennifer Anne , Sandstrom Kate , Alfes Celeste , Schiltz Nicholas K , Singer Mendel E , Rezaee Rod , Daly Barbara J. 
Published: May 2020

TPS12129 Background: Positive treatment outcomes and avoidance of complications are dependent to a large extent on the care provided by family members. However, family caregivers report feeling unprepared to assume the multiple, complex tasks of caregiving, including tracheostomy care, tube feedings, wound and colostomy care, pain management, and emotional support. Despite being a critical extension of the oncology healthcare team, training of caregivers to manage symptoms, deal with communication issues with the care recipients, and take care of their own physical and emotional health as caregivers, is not integrated into clinical practice. The purpose of this clinical trial is to measure the effect of a psychoeducational caregiver intervention that incorporates simulation techniques focused on skill development to improve caregiver and patient outcomes. Simulation, commonly used in training healthcare professionals, is a form of experiential learning that creates events or situations to mimic clinical situations. Use of simulation for skills training in family caregivers of patients with cancer is rarely studied. Methods: This two-group, randomized clinical trial, which opened to accrual in December 2019, will recruit 180 caregivers from University Hospitals Seidman Cancer Center. Patients must be receiving radiation therapy for a diagnosis of stage I - III cancers of the rectum, anus, and esophagus; stage III NSCLC; or stage I – IV A/B head/neck cancer. Adult caregivers must be identified by the patient as their primary caregiver, who is providing daily assistance and/or emotional support. The intervention involves three in-person, one-on-one sessions during radiation treatments. The control group is usual care. Data will be collected at baseline, at the end of radiation treatment, and 4 and 20 weeks post-radiation treatment. The primary outcome is caregiver anxiety at 20 weeks postradiation treatment. Other caregiver outcomes include depression, health-related quality of life [HRQOL], and fatigue. Patient outcomes (HRQOL and interrupted treatment course) and healthcare utilization outcomes (unplanned hospital admission, emergency room visits, and use of intravenous fluids) will be measured. The analysis will consist of linear mixed model repeated measures, mediation and moderation tests, and Poisson regression methods. Clinical trial information: NCT04055948 .
Implementing a clinical risk prediction tool for patients undergoing active cancer treatment.
Authors: Handley Nathan , Binder Adam , Li Michael , Rogers Aliya , Csik Valerie Pracilio 
Published: May 2020

TPS2086 Background: Acute care utilization (ACU), encompassing both emergency department visits and hospitalizations, is common in patients with cancer, with nearly three quarters of patients with advanced disease hospitalized at least once in the year after their diagnosis. Efforts to prospectively identify these patients prior to ACU have led to the development of a variety of scoring systems for specific cancer patient populations, including the elderly and those initiating palliative infusional chemotherapy. Prospectively identifying patients may enable early interventions to reduce ACU. However, few studies have demonstrated effective implementation of such prediction tools in clinical practice. We developed an oncology risk score (ORS) for active oncology patients (defined as patients with an active cancer diagnosis in the last 12 months who had a Medical Oncology encounter in a 180-day period ) to prospectively determine risk of ACU. Patients are defined as high risk (18% of patients, accounting for 57% of historical ACU), intermediate risk (25% of patients, accounting for 25% of ACU), or low risk (56% of patients, accounting for 18% of ACU) by the ORS. We are currently deploying a pragmatic implementation initiative to evaluate the impact of targeted nurse navigator (NN) outreach to patients defined as high risk for ACU by the ORS. Methods: The ORS is embedded within the health system electronic medical record. The ORS will be queried on a weekly basis. NNs will contact identified patients, prioritizing patients not yet identified by the navigation team by other means. Following chart review, NNs will either meet patients in person (if a visit is already planned within 24 hours) or complete standard navigation outreach and documentation (consisting of phone call and barrier assessment, as well as appropriate nursing intervention) if no visit is planned. NNs will determine follow up cadence based on clinical judgement. Efficacy will be determined using a case-control method. Case patients will be OCM patients defined as high risk by the ORS (historical n = 289); control patients will be non-OCM high risk patients (historical n = 388). The total number of patients in the case and control groups, as well as the proportion of patients in the group utilizing acute care, will be monitored over time. Proportion of high risk patients known to navigation will be tracked. ACU in medium and low risk groups will also be monitored. Targeted outreach to high risk patients using the ORS began on 2/5/2019.
Alliance A071701: Genomically guided treatment trial in brain metastases.
Authors: Brastianos Priscilla Kaliopi , Twohy Erin , Anders Carey K. , Iafrate A. John , Kaufman Peter A. , Cohen Justine Vanessa , Heist Rebecca Suk , Gerstner Elizabeth Robins , Kaufmann Timothy J. , Geyer Susan , Hoffman Laura , Kumthekar Priya , Barker Frederick G. , Carter Scott L. , Brown Paul D. , Galanis Evanthia 
Published: May 2020

TPS2573 Background: Brain metastases, most commonly derived from melanoma, lung and breast cancers, are the most common brain tumor, with approximately 200,000 cases diagnosed annually in the United States. Median survival is on the order of months. For patients with clinically symptomatic brain metastases, approximately half succumb due to intracranial progression. In preclinical work, we demonstrated that brain metastases and primary tumors are often genetically distinct with frequent alterations in the CDK and PI3K pathway (Brastianos, Carter et al. Cancer Discovery 2015). Methods: We are currently accruing to a prospective multi-arm phase II study of CDK, PI3K/mTOR, and NTRK/ROS1 inhibitors in patients with brain metastases harboring alterations associated with sensitivity to these inhibitors (abemaciclib, paxalisib and entrectinib), respectively. Patients with new, recurrent or progressive brain metastases are eligible for this trial. Previously obtained tissue from brain metastases and extracranial sites (primary or extracranial metastases) are screened for the presence of these alterations, and if present in both tumor sites, patients will receive the appropriate corresponding targeted treatment. Screening is carried out with the SNaPshot NGS assay, which is a fully validated clinical test designed and developed at the MGH Center for Integrated Diagnostics. The primary endpoint of response rate (RR) in the central nervous system as per RANO criteria will be evaluated separately for each inhibitor, stratified by histology within each arm. There will be 21 evaluable patients assigned to each of the CDK and PI3K inhibitor and tumor type cohorts (breast, lung and other) and 10 patients assigned to the NTRK/ROS1 inhibitor cohort (lung) for a total of 136 evaluable patients. Although current systemic therapy for brain metastases is often ineffective, we hypothesize that targeted therapies will demonstrate efficacy in patients harboring the appropriate mutations. This study represents a novel individualized therapeutic approach in brain metastases, a disease with a critical need for effective therapy. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org ; Genentech, Kazia Therapeutics Limited, Eli Lilly; Clinical trial information: NCT03994796 .
INDIGO: A global, randomized, double-blind, phase III study of vorasidenib (VOR; AG-881) vs placebo in patients (pts) with residual or recurrent grade II glioma with an isocitrate dehydrogenase 1/2 (IDH1/2) mutation.
Authors: Mellinghoff Ingo K. , Van Den Bent Martin J. , Clarke Jennifer Leigh , Maher Elizabeth Anne , Peters Katherine B. , Touat Mehdi , De Groot John Frederick , De La Fuente Macarena Ines , Arrillaga-Romany Isabel , Wick Wolfgang , Ellingson Benjamin M. , Schoenfeld Steven , Tai Feng , Le Kha , Lu Min , Steelman Lori , Hassan Islam , Pandya Shuchi Sumant , Wen Patrick Y. , Cloughesy Timothy Francis 
Published: May 2020

TPS2574 Background: Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options consist of surgery followed by observation (“watch and wait”) for pts with lower risk for disease progression or post-operative chemo-radiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (m IDH1/2) occur in approximately 70% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate (2-HG). VOR, an oral, potent, reversible, brain-penetrant inhibitor of mIDH1/2, was evaluated in 76 pts with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at doses of < 100 mg daily. Preliminary clinical activity was observed in non-enhancing glioma pts in both studies, most recently with an objective response rate (ORR) of 30.8% at 50 mg QD in the perioperative study and > 90% 2-HG suppression at this dose level relative to untreated control samples (Mellinghoff et al., J Clin Oncol 2019). Methods: Approximately 366 pts will be randomized 1:1 to VOR (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria include: age ≥12 years; grade 2 oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed m IDH1/2 status; ≥1 prior surgery for glioma within the previous 5 years but no other anticancer therapy; Karnofsky performance status ≥80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the VOR arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint is progression-free survival assessed by independent review. Secondary endpoints include safety and tolerability, tumor growth rate assessed by volume, time to next intervention, ORR, overall survival, quality of life assessed by the Functional Assessment of Cancer Therapy–Brain questionnaire, and plasma pharmacokinetics. Exploratory endpoints include seizure activity and neuro-cognitive function. Clinical data will be reviewed regularly throughout the study by an independent data monitoring committee. The study is currently enrolling pts in the US, with additional countries planned (NCT04164901). Clinical trial information: NCT04164901 .