bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal investigation of Distress Thermometer scores in patients with cancer.
Authors: Ullah Fauzia , Brugioni Emily , Gannon Matthew M , Smith Hayden L , Lukenbill Joshua Cole
Published: May 2020

e24200

Background: The Distress Thermometer (DT) is a tool used to evaluate distress among cancer patients. The DT can provide information for intervention recommendations such as social work, psychological, and other ancillary services. The National Comprehensive Cancer Network (NCCN) recommends recurrent use of the tool. The DT is widely used as a standard of care for an initial screening of cancer patients, but data on subsequent use is lacking. The aim of this research was to evaluate repeat DT scores in a heterogeneous cancer patient population. Methods: Clinical investigators conducted a longitudinal study of DT ratings for cancer patients receiving outpatient care at a community-based oncology subspecialty practice in a mid-sized city from 2018 to 2019. Study objectives included reviewing referrals and evaluating the relationship between the initial screening and the screening at the 6-month checkup. The Distress Thermometer was used (i.e., 0-10; zero is “no distress” and ten “extreme distress”) with scores of four or greater regarded as a signal of greater risk for patient distress. Results: The study sample included 79 patients with an average score of 4.3 and 4.0 at baseline and the 6-month screening, respectively. Patient referrals included physical and emotional therapy (n=1) or social/psychosocial worker assessment (n=26). Patients with a documented referral had a crude 1.7 (95% CI: 0.6, 3.3) greater point decrease in scores compared to patients not offered a service referral. When adjusting for baseline scores and the time between scores, referral accounted for 1% (95% CI: 0%, 14%) of variability in score changes, while baseline scores accounted for 40% (95% CI: 22%, 52%) and time accounted for 3% (95% CI: 0%, 14%). Conclusions: Study results reveal a possible decrease in higher scores from the initial screening to the 6-month check-up. Patients with a referral did not have their service utilization confirmed and this study failed to show an additional decrease in scores based on referrals when controlling for baseline score and time. Most previous research has focused on one specific cancer type. This study revealed the possible importance in understanding DT scores in a heterogenous cancer patient population. Furthermore, large scale research is needed to confirm preliminary data and further expound on distress at initial and subsequent screenings after interventions. A better understanding of this content area may function to improve future care and patient well-being.
A phase III trial of capivasertib and paclitaxel in first-line treatment of patients with metastatic triple-negative breast cancer (CAPItello290).
Authors: Schmid Peter , Cortes Javier , Robson Mark E. , Iwata Hiroji , Hegg Roberto , Nechaeva Marina , Xu Binghe , Verma Sunil , Haddad Vincent , Rodrigo Imedio Esteban , Schiavon Gaia , Foxley Andrew , Park Yeon Hee
Published: May 2020

TPS1109

Background: Therapeutic options for patients with metastatic triple-negative breast cancer (TNBC) are limited to sequential chemotherapy, although recent advances with novel agents have been made for specific subgroups (PD-L1 inhibitor atezolizumab in combination with nab-paclitaxel in patients with PD-L1-positive tumors and PARP inhibitors in patients with germline BRCA mutations). The PI3K/AKT/PTEN signaling pathway is often activated in TNBC, mainly through activating mutations in PIK3CA or AKT1 and/or inactivating alterations in PTEN. The phase II PAKT study (NCT02423603) demonstrated that addition of the oral AKT inhibitor capivasertib to first-line paclitaxel resulted in significantly longer progression-free survival (PFS) and overall survival (OS) in patients with advanced TNBC, especially in patients with PIK3CA/AKT1/PTEN-altered tumors (Schmid et al, 2019). This phase III trial (NCT03997123) will further evaluate the efficacy and safety of capivasertib in combination with paclitaxel in first-line treatment of patients with metastatic TNBC in an unselected population and will also explore potential predictive markers of sensitivity to the combination of paclitaxel and capivasertib. Methods: Eligible patients for this double-blind, randomized, placebo-controlled trial must have metastatic TNBC or locally advanced disease not amenable to resection with curative intent. Patients must be candidates for single-agent taxane therapy and have received no prior systemic therapy for locally advanced inoperable or metastatic disease. Prior chemotherapy in the (neo)adjuvant setting must be completed ≥12 months prior to enrollment. Patients will be randomized 1:1 to paclitaxel 80 mg/m2 (days 1, 8 and 15) with either capivasertib 400 mg twice daily or placebo (days 2–5, 9–12 and 16–19) every 28 days, until objective radiologic disease progression as defined by RECIST 1.1, unacceptable toxicity or death. Stratification factors will be prior adjuvant chemotherapy, visceral versus non-visceral disease, and geographic region. Post-randomization central testing of tumor tissue (collected prior to enrollment) will be carried out to identify predictive markers of sensitivity to treatment. The primary endpoints of this study are PFS and OS. Secondary endpoints include safety and tolerability, time to second progression or death, objective response rate, duration of response, and clinical benefit rate. Enrollment for this study started in May 2019. Clinical trial information: NCT03997123 .
Effects of an e-home based symptom management and mindfulness training program on quality of life in breast cancer survivors.
Authors: Cheng Karis Kin-Fong , Siah Rosalind , Zhang Melvyn , Keng Shian-Ling , Wong Wan-Hua , Ho Roger , Lim Hsuen Elaine
Published: May 2020

TPS12130

Background: The first five years post-treatment for breast cancer are a critical phase, when the survivors may face a multitude of problems, including persistent and/or late-emerging symptoms following the cancer and its treatment, psycho-social distress associated with the risk of cancer recurrence, chronic uncertainty and social disruption. Thus, this trial will answer the research questions of 'Will the combined symptom management and mindfulness-based training programme be a promising approach to assist women with breast cancer in transition from treatment to survivorship?', and 'Since breast cancer survivors have infrequent clinical follow-up, will e-Home based system provide a feasible option for post-treatment care?' Methods: We aim to develop an e-Home based symptom management and mindfulness training programme for breast cancer survivors and to determine its effects on the endpoints including quality of life, symptom distress, psychosocial adjustment, psychological morbidity, and unplanned outpatient attendance or hospitalisation in breast cancer survivors. (ClinicalTrials.gov Identifier: NCT02931864) We employ a randomised clinical trial with four study arms (with 47 subjects, who have completed cancer treatment for stage 0 to 3 breast cancer between 6 months to 5 years previously, in each arm) together with a process evaluation; group 1 (usual care), group 2 (experimental group: five weekly sessions of online symptom management + mindfulness training programme and usual care), group 3 (comparison group 1: online symptom management programme and usual care), and group 4 (comparison group 2: online mindfulness training programme and usual care). Subjects will complete questionnaires measures of 6-item Social Support Questionnaire, Breast Cancer Survivor Self- Efficacy Scale, the Quality of Life-Cancer Survivor Scale, Memorial Symptom Assessment Scale, Psychosocial Adjustment to Illness Scale, short version of the Fear of Recurrence Scale, Hospital and anxiety Depression Scale, and Five Facet Mindfulness Questionnaire at baseline, at 8 weeks from time 1 (time 2), at 12 weeks from time 1 (time 3) and at 24 weeks from time 1 (time 4). Intention-to-treat approach will be used. Repeated measures analysis of variance will be used to examine the differences on outcome measures among the experimental, comparison, and control groups across study time points. Currently, 162 of 188 planned subjects have been enrolled and the trial continues as planned. Clinical trial information: NCT02931864 .
ApricityRx companion digital therapeutic for evidence-based mitigation and phenotype-linked molecular characterization of irAEs in patients receiving immune checkpoint therapy (ICT).
Authors: Campbell Matthew T , Zhang Tian , Chin Lynda , Warner Allison Betof , Mathew Matthen
Published: May 2020

TPS2089

Background: Presentation of immune-related adverse events (irAEs) is heterogeneous and unpredictable in patients receiving immune checkpoint therapy (ICT). ICT has been approved for cancer patients as single agent, combination of dual ICT, ICT plus chemotherapy, and ICT plus targeted therapy. Given the ever increasing complexity in recognizing and managing irAEs, coupled with the lack of skilled resources and clinical experience in real world practice, there is increasing demand for digital solutions that can detect early toxicity and support evidence-based interventions in real world practice. To this end, we have developed ApricityRx, a companion digital therapeutic for end-to-end irAE management. In addition to (i) teaching patients about immune-related toxicities and (ii) empowering them to monitor key symptoms and vital signs, ApricityRx continuously analyzes the combined patient-reported data and longitudinal EMR data to (iii) detect symptom-triggers and lab test-triggers of irAEs, and (iv) activate the clinical team to triage, evaluate and treat in a timely fashion, while (v) providing access to synthesized longitudinal patient information and expert guidance on evidence-based management and care. In a feasibility trial conducted in a community setting, we demonstrated two-thirds of the study participants completed on average 5 eCheck-ins per calendar week (overall average 4 times per week), with 5% of the check-ins resulting in notifications alerting the clinical team to evaluate for the early signs of an irAE. Methods: To accelerate translational research in irAEs and to develop predictive biomarkers for risk stratification, we are launching a single-arm, open-label study that utilizes ApricityRx in patients receiving ICT alone or in combination. The objectives of the study will include (i) defining the operative characteristics of ApricityRx as an irAE mitigation strategy; (ii) identifying patients and time points for phenotype-triggered biospecimen collection and molecular characterization. The study aims to enroll initially up to 100 participants per site, with a total target of 1,000.
Phase I/II study of T-DM1 alone versus T-DM1 and metronomic temozolomide in secondary prevention of HER2-positive breast cancer brain metastases following stereotactic radiosurgery.
Authors: Zimmer Alexandra Dos Santos , Steinberg Seth M. , Smart DeeDee Kay , Gilbert Mark R. , Armstrong Terri , Burton Eric , Houston Nicole D. , Biassou Nadia , Gril Brunilde , Brastianos Priscilla Kaliopi , Carter Scott L , Lyden David , Lipkowitz Stanley , Steeg Patricia Schriver
Published: May 2020

TPS2572

Background: We demonstrated that low doses of temozolomide (TMZ) administered in a prophylactic, metronomic fashion significantly prevented development of brain metastases in murine models of breast cancer. Based on these findings, we developed a secondary-prevention clinical trial. Methods: Phase I is a standard 3+3 design: T-DM1 3.6mg/kg IV every 21 days plus TMZ 30, 40 or 50 mg/m2 daily, to identify the maximum tolerated dose (MTD) of the combination, and is completing accrual, with 9 patients accrued, currently on the third and last dose level. Phase II will randomize patients to T-DM1 3.6mg/kg versus T-DM1 3.6mg/kg plus TMZ at recommended phase 2 dose (RP2D), to evaluate if addition of TMZ improves the recurrence-free incidence from distant new brain metastases at one year from 50% to 65%. Patients will undergo radiology guided lumbar puncture at baseline and after 6 weeks of treatment (C3D1) for correlative studies, brain MRI, systemic restaging CTs, and questionnaires for evaluation of symptoms and quality of life. Eligibility: HER2+ breast cancer with brain metastases (up to 10 lesions), treated with SRS and/or resection ≤12 weeks before enrollment, no leptomeningeal metastases, no previous WBRT, ECOG ≤2 and adequate organ and marrow function. Biomarkers, including cell free DNA from CSF, serum and tumor block, exosomal DNA, serum markers for neuroinflammation, and patient reported outcomes, will be analyzed in an exploratory fashion. Target accrual: up to 18 patients in phase I and 98 in phase II. Clinical trial information: NCT03190967 .
A phase Ib, open-label, dose-escalation trial of naptumomab estafenatox (Nap) in combination with durvalumab (MEDI4736) in subjects with selected advanced or metastatic solid tumors.
Authors: Geva Ravit , Maurice-Dror Corinne , Moskovitz Mor Tal , Ben-Ami Eitan , Raphael Ari , Lorber Ilana , Rozencweig Marcel , Golan Talia
Published: May 2020

TPS3160

Background: Immunotherapy with the anti-PD-(L)1 checkpoint inhibitors (CPIs) has been largely ineffective in so-called non-immunogenic “cold tumors”. Facilitating T cell infiltration is necessary to invoke an immune response which may be augmented or complemented by the activity of CPIs like durvalumab. Selective T cell Redirection Proteins (STRs) are fusion proteins that consist of genetically engineered Superantigen (Sag) linked to Fragment antigen binding (Fab) moieties directed to tumor-associated antigens. Nap is a first in class STR compound, recognizing the tumor-associated oncofetal antigen 5T4, whereas the SAg moiety selectively engages the T cell receptor β variable (TRBV) 7-9. Nap has been shown to induce specific T cells expansion, activation and infiltration into the tumor in pre-clinical and clinical studies. Pre-clinical data demonstrated that the combination of STR with CPI may lead to long term durable responses not possible in most patients receiving single agent CPI therapy and suggests that combining CPIs with STR may be a promising therapeutic strategy for patients with solid tumors. Methods: Patients will be treated with the combination of Nap and durvalumab using a flat dose of durvalumab (1120 mg) and the 3+3 design for Nap dose escalation (2, 5, 10, 15 and 20 mcg/kg). The MTD of Nap for the combination treatment will be established based on DLTs occurring during the first treatment cycle. The dose escalation part will be followed by MTD expansion cohort in which 10–15 patients will be treated with MTD of Nap and 1120 mg durvalumab (Clinical trial registry number NCT03983954). Major eligibility criteria include patients with pretreated advanced or metastatic, 5T4 expressing solid tumors, including patients previously progressed on CPI therapy. As of January 2020, enrollment to dose levels 2, 5 and 10 mcg/kg has been completed without DLT, enrollment to dose level 15 mcg/kg will start on February 2020. Clinical trial information: NCT03983954 .
AST-008: A novel approach to TLR9 agonism with PD-1 blockade for anti-PD-1 refractory Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (CSCC).
Authors: Milhem Mohammed M. , Perez Cesar Augusto , Hanna Glenn J. , Wise-Draper Trisha Michel , Bhatia Shailender , Bexon Alice Susannah , Daniel Weston L , O'Day Steven
Published: May 2020

TPS3164

Background: AST-008 is a potent spherical nucleic acid configuration of a toll-like receptor (TLR) 9 agonist oligonucleotide being developed for the treatment of MCC and CSCC in patients (pts) progressing on immune checkpoint inhibitor (CPI) monotherapy. Previously presented data suggests AST-008 elicits a Th1-type cytokine response and immune cell activation. This parallel-arm phase II design will permit assessment of efficacy in two advanced skin cancers with high unmet medical need. Methods: The study has an open label, multicenter phase Ib/II dose escalation/expansion design. The phase 1b dose escalation used a 3+3 design with increasing doses of intratumoral (IT) AST-008 plus standard flat dose pembrolizumab. The phase II dose expansion is using the recommended regimen (RP2D) of IT AST-008 plus flat dose pembrolizumab or cemiplimab to treat two cohorts of pts with advanced/metastatic MCC or CSCC, respectively. The key objective of the phase II expansion is to provide an estimate of preliminary efficacy of IT AST-008 with pembrolizumab or cemiplimab in pts whose disease progressed on a single-agent CPI therapy. Endpoints also include safety, pharmacokinetic and pharmacodynamic assessments. Pts must have at least two evaluable lesions by RECIST v1.1. One or more lesions may be injected with AST-008, but one lesion (the “witness” lesion) must remain un-injected throughout the study to differentially assess effects of AST-008 on the injected and witness lesions. The RP2D of AST-008 was derived from the dose escalation phase together with pembrolizumab. That RP2D is being used not only in the MCC cohort where AST-008 is combined with pembrolizumab, but also in the CSCC cohort where AST-008 is combined with cemiplimab. To ensure safety of the AST-008/cemiplimab combination, the first 6 pts in the CSCC cohort will be monitored for dose limiting toxicities through the first 5 weeks of dosing, and then the data review committee will assess safety before approving additional patient enrollment to that cohort. Each expansion cohort will enroll up to 29 pts with a Simon two-stage optimal design. In the first stage, 10 pts will be accrued. If there are 0 responses in these 10 pts, enrollment in that arm will be stopped. Otherwise, 19 additional pts will be accrued for a total of 29. The null hypothesis will be rejected if 4 or more responses are observed in 29 pts. This design yields a type I error rate of 0.05 and power of 80% when the true response rate is 20%. The planned phase II enrollment is 58 pts across about 15 US-based sites. Clinical trial information: NCT03684785 .
A phase I/II, open-label, dose-escalation, and cohort-expansion study evaluating the safety, pharmacokinetics, and therapeutic activity of OBI-999 in patients with advanced solid tumors.
Authors: Tsimberidou Apostolia Maria , Ajani Jaffer A. , Hsu Pei , Chen I-Ju , Pearce Tillman E.
Published: May 2020

TPS3657

Background: Aberrant glycosylation is a hallmark of cancer. Glycosphingolipids (GSLs), glycans conjugated to a lipid (ceramide) core, are essential for the recruitment of immune-related proteins to specific membrane microdomains. Globo H (GH) is a GSL found on normal cells but highly overexpressed on various epithelial tumors playing a role in tumor development and progression. GH is a promising target for immunotherapy. OBI-999 is an ADC composed of a human recombinant immunoglobulin G (IgG) monoclonal antibody that selectively and specifically binds to GH, attached by a linker to the antimitotic agent monomethyl auristatin E (MMAE). Its mechanism of action is based on tumor-selective delivery of MMAE to GH-expressing tumors with subsequent tumor cell death. Preclinical studies demonstrated that OBI-999 antibody binds specifically to the GH antigen, and antitumor efficacy was noted in breast, gastric, pancreatic, and lung cancer xenograft models. The pharmacokinetics (PK) of OBI-999 were determined in normal and tumor-bearing mice, rats, and monkeys. Exposure of OBI-999 increased proportionally with dose. No sex difference or accumulation was seen. The primary objectives are to determine dose limiting toxicities (DLTs), the maximum tolerated dose (MTD), and the phase 2 recommended dose (P2RD). The secondary objectives are to assess the rates of objective response and clinical benefit, the duration of progression-free survival, the immunogenicity of OBI-999, and the PK and pharmacodynamics (PD) of OBI-999 and MMAE. Methods: In Part 1, a "3+3" dose-escalation part of the study, up to 30 patients with advanced solid tumors refractory to ≥1 line of systemic therapy, who cannot tolerate standard therapy, or for whom no standard treatment is available, regardless of GH status will be treated. OBI-999 will be administered as a 60-minute IV infusion using a dose range of 0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg on day 1 of every 21-day cycle. In Part 2, the cohort-expansion portion of the study, patients will be treated at the MTD or at a lower RP2D as determined by cumulative toxicities and tolerability profile. The study will determine the preliminary clinical activity and safety of OBI-999 in up to 155 patients with advanced solid tumors, pancreatic, gastric, esophageal, and colorectal cancer according to a Simon two-stage phase 2 design. Patients must have GH overexpression defined as an H-score of ≥100 according to an FDA Investigational Device Exempt (IDE) validated IHC assay. Clinical trial information: NCT04084366 .
TRACC: Tracking mutations in cell-free DNA to predict relapse in early colorectal cancer—A randomized study of circulating tumour DNA (ctDNA) guided adjuvant chemotherapy versus standard of care chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer (CRC).
Authors: Anandappa Gayathri , Starling Naureen , Peckitt Clare , Bryant Annette , Begum Ruwaida , Carter Paul , Hatt Shelby , Khakoo Shelize Sadrudin , Turner Andrea , Kidd Shannon , Duncan Julie , Hobbis Laura , Giorgakoudi Kyriaki , Smalley Michaela , Lowery David , Wheatstone Pete , Chau Ian , Hubank Michael , Cunningham David
Published: May 2020

TPS4120

Background: Adjuvant chemotherapy (ACT) is routinely offered to patients with high risk (HR) stage II or stage III CRC following potentially curative surgery. Over 50% of stage III and > 80% of stage II patients are cured by surgery alone but are being exposed to unnecessary chemotherapy with short- and long-term side effects. Post-operative ctDNA identifies minimal residual disease (MRD) after surgery in CRC. Our national study, TRACC, compares ctDNA guided versus standard of care (SoC) decision making in patients undergoing ACT. Methods: This is a UK-wide, multi-centre, prospective, two-arm, randomised trial. Patients with HR risk stage II or stage III CRC who have undergone R0 resection and have detectable ctDNA in their pre-surgical sample are eligible. Patients who undergo neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer with detectable ctDNA pre-CRT are also eligible. Patients are randomised in a 1:1 ratio to receive either SoC ACT or ctDNA guided ACT. In the ctDNA guided arm, patients who are ctDNA negative post-operatively have chemotherapy de-escalated i.e., 3 months(m) of Capecitabine and Oxaliplatin (CAPOX) doublet ACT is reduced to 3 m single agent Capecitabine; 6 m single agent Capecitabine reduced to no chemotherapy. In this group, ctDNA is re-tested at 3 months and if detectable, patients receive 3 months of CAPOX. Primary end-point is 3-year disease free survival (DFS). Secondary end-points include overall survival, neurotoxicity, quality of life and health economics. Based on a standard 3-year DFS of 75% in SoC ACT arm, to demonstrate a non-inferiority margin of 1.25, 810 patients are required per arm (85% power, α = 0.1). Stratification is by tumour staging and site of primary tumour. Target accrual is over 4 years. The study opened to recruitment in January 2020 and is supported by the MRC-NIHR Efficacy and Mechanism Evaluation Grant ( NIHR128529 ). Clinical trial information: NCT04050345 .
A phase II trial of PD-1 inhibition with INCMGA00012 in patients with previously treated unresectable or metastatic adenosquamous pancreatic cancer.
Authors: Jakubowski Christopher , Thompson Elizabeth D , Wang Hao , Walker Rosalind , Jaffee Elizabeth M. , Azad Nilofer Saba
Published: May 2020

TPS4662

Background: Adenosquamous pancreatic cancer (ASQ) constitutes 1-5% of all pancreatic cancers and compared to pancreatic adenocarcinoma (PDAC) has a worse survival. ASQ has glandular and squamous histologic components and given its rarity and aggressiveness, in practice there is no current standard regimens for ASQ. Unfortunately, checkpoint blockade has had an overall disappointing impact on survival in PDAC. In an effort to identify a patient subgroup most likely to respond to immunotherapy, the immune tumor microenviroment (TME) in ASQ was evaluated. Tissue microarrays from archived ASQ samples were first created. Then immunocytochemistry (IHC) staining for immune cells and immune checkpoint proteins was performed. PD-L1 expression and the combined presence of PD-L1+, IDO+, LAG3+, and VISTA+ was seen. All ASQ cases had some degree of tumor infiltrating lymphocytes (TIL, including CD8+ T-cells). Furthermore, PD-L1 and other checkpoint positivity correlated with increased TIL. These findings suggest the presence of adaptive immune resistance. This is in contrast to standard PDAC, in which the expression of immune checkpoints is rarely accompanied by increased effector T-cells. Methods: We are conducting a multiple-center, single arm, phase II clinical trial to evaluate PD-1 inhibition with INCMGA00012 in locally advanced unresectable and metastatic ASQ patients. INCMGA00012 is a humanized monoclonal antibody antagonistic to PD-1. The primary objective is to determine the disease control rate at 4 months using RECIST 1.1. The study is planned with 21 evaluable subjects and allows early termination for lack of efficacy. Patients have a pre-treatment biopsy followed by INCMGA00012 500 mg on Day 1 of each cycle (every 4 weeks). A second biopsy will occur eight weeks later. Eligibility criteria includes histologically- or cytologically-proven adenosquamous carcinoma of the pancreas by central pathologic review and patients must have received (or been intolerant to or ineligible for) at least 1 prior line of cytotoxic chemotherapy and received no more than 2 prior systemic treatments. Patients with known MSI-H/dMMR status are excluded. Exploratory objectives include examining changes in the TME checkpoint expression and immune cell infiltrate in the biopsies via IHC and RNA expression studies. The clinical study was activated in February 2020. Clinical trial information: NCT04116073 .
PD-1 antibody combined with paclitaxel (albumin bound) and gemcitabine as first-line therapy in patients with metastatic pancreatic cancer.
Authors: Cui Jiujie , Yao Jiayu , Wang Yu , Liang Yiyi , Wang Yongchao , Jiao Feng , Zhang Xiao , Han Ting , Mao Tiebo , Xia Qing , Xiao Xiuying , Yang Haiyan , Wang Li-Wei
Published: May 2020

TPS4665

Background: Pancreatic cancer is a malignant tumor with limited therapeutic strategies and poor prognosis. About 60% of the patients have metastasis disease at time of diagnosis and lose the opportunity for surgery. Thus, therapy based on drugs becomes a vital part in pancreatic cancer. In 2013, MPACT showed that albumin-bound paclitaxel combined with gemcitabine in the treatment of metastatic pancreatic cancer could increase the mOS from 6.6 months to 8.7 months (HR = 0.72, 95% CI: 0.62-0.83; P < 0.001). Nowadays, the immunosuppressive checkpoint inhibitors acting on PD-1/PD-L1 pathway have shown a significant efficacy in enhancing tumor immune surveillance and anti-tumor immune response. In 2018, two studies reported in ASCO showed the preliminary efficacy of albumin paclitaxel, gemcitabine and PD-1 inhibitor in the treatment of advanced pancreatic cancer. Among patients who have not received treatment before, the disease control rate was even up to 100%. Therefore, this study will further explore the domestic PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as the first-line treatment of advanced pancreatic cancer among Chinese pancreatic cancer patients. Methods: This is a prospective, single-armed, exploratory, investigator initiated trial to explore the efficacy and safety of PD-1 antibody combined with albumin-bound paclitaxel and gemcitabine as first-line treatment of metastatic pancreatic cancer. This study is, to our knowledge, the first one to test the efficacy and safety of PD-1 antibody on metastatic pancreatic cancer patients among Chinese population. Survival index is median survival estimated by Kaplan-Meier and draw the survival curve. The response rate was compared by χ 2 test / Fisher test. All primary and secondary outcomes will be analyzed on the full analysis set. PD-1 antibody, 200mg, D1 administration; paclitaxel (albumin binding type), 125mg/m2, D1, 8 days administration; gemcitabine, 1000mg/m2, D1, 8 days administration, every 21 days as a cycle and PD-1 antibody (200mg, D1, every 21 days) single drug maintenance treatment is given after the completion of 6 cycle chemotherapy. Major eligibility criteria is that each participant must have metastatic pancreatic cancer confirmed by histology or cytology and has never received systemic anti-tumor therapy before. So far, 11 of planned 20 patients have been enrolled. Clinical trial information: NCT04181645 .
Improving FOLFIRINOX safety in pancreatic cancer patients through multidimensional remote monitoring and proactive care using a domomedecine mobile platform.
Authors: Bouchahda Mohamed , Komarzynski Sandra , Ulusakarya Ayhan , Attari Amal , Duprès Alban , Breda Gabrièle , Fritsch Agnès , Adam René , Levi Francis
Published: May 2020

TPS4673

Background: Pancreatic cancer is a poor prognosis and fast-growing cancer, whose five-year survival is 6% in Europe and the US. FOLFIRINOX has been established as the reference medical treatment for this disease worldwide, yet it also causes leuko-neutropenia, thrombocytopenia, diarrhea, anorexia, asthenia, weight loss, and peripheral sensory neuropathy. Its indication is usually limited to patients having a WHO performance status of 0 or 1. This treatment is often interrupted once Grade 3-4 clinical or hematological toxicities occur, resulting in poor patient performance status and quality of life. Presently, no prospective study monitor and evaluate the qualitative and quantitative effects of FOLFIRINOX on the daily life of pancreatic cancer patients in real-time. Such monitoring would provide early warning signals for the identification of any improvement or deterioration of the patient condition. Whenever necessary, proactive interventions would be triggered to avoid emergency hospitalization for severe adverse events and to enhance treatment compliance. Methods: Our study involves the use of the mobile e-Health platform PiCADo (JMIR 2018) to track and analyse circadian rhythms, symptoms, and body weight in real time in 45 advanced pancreatic cancer patients at 4 centres. The patients are continuously telemonitored for rest-activity, temperature and 3D-orientation via a BLE sensor during the six weeks following the first FOLFIRINOX course. Patients weigh themselves daily on a BLE scale and self-rate their symptoms using a touchscreen on GPRS tablet. Alerts are generated according to preset yet modifiable thresholds of automatically computed critical parameters. From these data, we will evaluate the rate of emergency hospital admissions and the admission-free survival, the rates of severe adverse events, patients’ symptoms dynamics, and their relations with the disruption of the patients’ circadian rhythm. Patient satisfaction and research experience will also be assessed, since engagement is at the core of the success of the approach. The results will guide a future randomized trial comparing standard pancreatic cancer patient care with a personalized FOLFIRINOX approach, including chronotherapy delivery. Support: Ramsay-Sante, Altran.
A phase III randomized study of neoadjuvant chemotherapy (NAC) alone or in combination with nivolumab (NIVO) ± linrodostat mesylate, followed by adjuvant postsurgical NIVO ± linrodostat, in cisplatin-eligible muscle invasive bladder cancer (MIBC).
Authors: Sonpavde Guru , Necchi Andrea , Gupta Shilpa , Steinberg Gary D. , Gschwend Juergen , Van Der Heijden Michiel Simon , Richiero Audrey , Lambert Alexandre , Raybold Bradley , Gajavelli Srikanth , Zardavas Dimitrios , Galsky Matt D.
Published: May 2020

TPS5091

Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible, muscle invasive BC (MIBC), the recommended tx is cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, supporting the therapeutic pursuit of the PD-1/PD-L1 axis. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. Linrodostat mesylate, a selective, potent, once-daily oral IDO1 inhibitor that works to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + linrodostat in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± linrodostat followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + linrodostat (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320 .
PDIGREE: An adaptive phase III trial of PD-inhibitor nivolumab and ipilimumab (IPI-NIVO) with VEGF TKI cabozantinib (CABO) in metastatic untreated renal cell cancer (Alliance A031704).
Authors: Zhang Tian , Ballman Karla V. , Choudhury Atish Dipankar , Chen Ronald C. , Watt Colleen , Wen Yujia , Shergill Ardaman , Zemla Tyler J. , Emamekhoo Hamid , Vaishampayan Ulka N. , Morris Michael J. , George Daniel J. , Choueiri Toni K.
Published: May 2020

TPS5100

Background: First-line treatment of mRCC has rapidly changed to include IPI-NIVO or CABO, with clinical benefit of each based on the Checkmate 214 and CABOSUN (A031203) trials. Combination immunotherapy with VEGF therapies has shown benefit over sunitinib in the JAVELIN 101 and KEYNOTE 426 trials. It is yet unclear which patients (pts) benefit most from combination immunotherapy-VEGF inhibitors, and the optimal sequence of drugs. Methods: In an adaptive, randomized, multicenter phase 3 trial (Alliance A031704, PDIGREE), pts start treatment with induction IPI 1 mg/kg and NIVO 3 mg/kg intravenously (IV) once every 3 weeks. Key inclusion criteria include clear cell mRCC, International Metastatic RCC Database Consortium (IMDC) intermediate or poor risk, Karnofsky performance status > 70, and no prior treatments for mRCC. Based on 3-month radiographic assessment (after completing IPI-NIVO combination), pts with complete responses (CR) undergo maintenance NIVO 480 mg IV every 4 weeks; pts with progression of disease (PD) switch to CABO 60 mg oral daily; pts with non-CR/non-PD are randomized to NIVO 480 mg IV every 4 weeks versus NIVO 480 mg IV every 4 weeks with CABO 40 mg oral daily. Randomization is stratified by IMDC risk criteria and presence of bone metastases. The primary endpoint of the study is overall survival (OS). We hypothesize that 3-year OS will improve to 70% for NIVO-CABO compared to 60% for NIVO alone; to achieve 85% power with a two-sided alpha of 0.05 and exponential distribution, 696 patients will be randomized. Accounting for 30% patients with either CR or PD, and 5% dropout from toxicity, up to 1046 pts will be enrolled. Key secondary endpoints include progression-free survival, 12-month CR rate, overall response rate based on RECIST 1.1 and irRECIST criteria, and toxicity profiles. Quality of life will be assessed based on the FKSI-19, PROMIS-fatigue, and EQ5D-5L questionnaires. Biomarkers associated with CR, tissue-based and plasma-based biomarkers will be assessed. Updated enrollment through May 2020 will be presented. Clinical trial information: NCT03793166 .
A multicenter, randomized, controlled phase II study: Efficacy and safety of PSMA-targeted radioligand therapy I-131-1095 (1095) plus enzalutamide (enza) in 18F-DCFPyL PSMA scan avid, metastatic castration-resistant prostate cancer (mCRPC) patients post-abiraterone (abi) progression (ARROW).
Authors: Yu Evan Y. , Laidley David , Pouliot Frederic , Probst Stephan , Sabbagh Robert , Esposito Giuseppe , Saad Fred , Sartor A. Oliver
Published: May 2020

TPS5596

Background: PSMA is a transmembrane glycoprotein expressed in normal human prostate epithelium at low levels, but highly upregulated in metastatic prostate cancer (PC). 18F-DCFPyL is a novel PSMA-targeted PET imaging agent that has shown highly promising diagnostic performance for detection of metastatic disease, with potential to identify disease amenable to theranostic targeting. 1095 is a novel PSMA-targeted small molecule that binds to the extracellular domain of PSMA selectively with high affinity. The complex is internalized, allowing the beta emitter, I-131, to kill PC cells. Methods: ARROW is an open-label, randomized (2:1) trial of enza plus 1095 or enza alone in pts with progressive mCRPC who previously received abi. ~120 pts (80: 1095 + enza; 40: enza alone) will be treated at ~40 sites in the US and Canada. Eligible male pts must be at least 18 yo with metastatic disease documented by bone scan or soft tissue lesions measurable per RECIST 1.1 on CT/MRI, be PSMA-avid as determined by 18F-DCFPyL PET/CT, have evidence of biochemical or radiographic progression on abi, and be ineligible for or refuse to receive chemotherapy. Pts will receive enza (prescribed per approved labeling) with or without 1095 (100 mCi dose, followed by up to 3 additional dose(s) administered at least 8 weeks apart, as determined by dosimetry evaluation and occurrence of dose-limiting events). The primary objective is to determine the efficacy of 1095 plus enza compared to enza alone, based on PSA response (confirmed PSA decline ≥50%) rate according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Additional objectives include objective response rate based on PCWG3-modified RECIST 1.1, progression-free survival (PFS) defined as the first occurrence of radiographic progression (PCWG3-modified RECIST 1.1), unequivocal clinical progression, or death from any cause, duration of response, overall survival, and the safety and tolerability of 1095 radioligand therapy. Clinical trial information: NCT03939689 .
Understanding and predicting fatigue, cardiovascular (CV) decline & events after breast cancer treatment (UPBEAT): A prospective multi-center wake forest NCORP research-base study.
Authors: Dent Susan Faye , Reding Kerryn , Lesser Glenn Jay , Klepin Heidi D. , Wagner Lynne I. , Kitzman Dalane , Brubaker Peter H. , Mihalko Shannon , Avis Nancy E. , Winkfield Karen Marie , Ky Bonnie , Crotts Teresa , Kikuchi Robin , Calhoun Tonya , Hundley W. Gregory
Published: May 2020

TPS602

Background: Modern treatment for breast cancer (BC) has led to improved survival; however, this improvement can be offset by an increase in cancer therapy-related morbidity and mortality. Over one-third of early stage BC patients treated with cancer therapy experience CV injury, left ventricular (LV) dysfunction, exercise intolerance, or fatigue. CV disease is a leading cause of mortality in BC survivors. There is limited information on the time course and long-term CV health of BC survivors. UPBEAT, a multicenter study, will prospectively evaluate CV risk factors and outcomes in early stage BC patients, treated with modern anticancer therapies. This will facilitate evaluation of primary CV prevention strategies in this patient population. Methods: This is a prospective cohort study of 840 patients with early stage (I-III) BC treated with chemotherapy +/- radiation and 160 controls. Baseline and serial longitudinal measures will examine the influence of cancer treatment on CV function, exercise capacity and fatigue, and the future development of CV events. The comprehensive assessment includes: ascertainment of cardiac biomarkers, CV risk factors, comorbidities, functional status (e.g., disability measures, expanded short physical performance battery), neurocognitive tests, behavioral risk factors, socio-demographics, and quality of life at baseline, 3-, 12-, and 24-mos. Outcomes measured at the same time points include a deep phenotyping of CV dysfunction (via cardiac MRI assessing LV end diastolic volume, LV end systolic volume, LV ejection fraction, myocardial strain, strain rate, left atrial volumes and mass, and aortic stiffness), exercise intolerance (submaximal as 6-minute walk test and maximal as VO2 peak via cardiopulmonary exercise test), and fatigue (via FACT-F). Eligibility criteria: age > 18 years; ECOG 0-2, able to walk without symptoms; receiving chemotherapy +/- HER2 targeted agent(s). To date, 244 participants are enrolled through 12 NCORP or ECOG-ACRIN sites. An additional 7 sites are onboarding and will be enrolling later in the year. Participants will be followed for 9 years with active surveillance of CV events (i.e., heart failure, myocardial infarction, stroke, all-cause and CV death). EA NCORP Grant: 2 UG1 CA189828 06; Research Base Grant: 2UG1 CA189824; R01: 1R01CA199167. Clinical trial information: NCT02791581 .
Primary cytoreductive surgery with or without Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for FIGO stage III epithelial ovarian cancer: The OVHIPEC-2 trial in progress.
Authors: van Stein Ruby M. , Koole Simone N. , Sikorska Karolina , Barton Desmond P. , Perrin Lewis , Brennan Donal , Zivanovic Oliver , Mosgaard Berit J. , Fagotti Anna , Colombo Pierre-Emmanuel , Retel Valesca P. , Sonke Gabe S. , Van Driel Willemien J. ,   The International OVHIPEC-2 Steering Committee and The Dutch OVHIPEC group
Published: May 2020

TPS6100

Background: The addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. The effect of HIPEC remains undetermined in patients who are eligible for primary cytoreductive surgery. We hypothesize that the addition of HIPEC to a complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery improves overall survival in patients with FIGO stage III ovarian cancer. Methods: This international, randomized, open-label, phase III trial enrolls patients with newly diagnosed, histological proven FIGO stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with resectable umbilical, spleen or local bowel lesions may be included. Following complete or near-complete primary cytoreduction, patients are intra-operatively randomized (1:1) to receive HIPEC or no HIPEC. Patients in both study arms will receive six courses of adjuvant carboplatin-paclitaxel and maintenance PARP-inhibitor or bevacizumab according to current guidelines. The primary endpoint is overall survival. To detect a Hazard Ratio of 0.67 in favor of HIPEC, 200 overall survival events are required. Assuming that accrual will be completed in 60 months, and 12 months additional follow-up, 538 patients need to be randomized. All randomized patients will be included in the analysis for overall survival according to the intention to treat principle. Pre-specified subgroup analyses will be performed based on stratification factors (peritoneal cancer index at start of surgery, completeness of surgery), histologic subtype (high-grade serous versus other), and BRCA mutation (BRCA1/2 mutation versus wildtype). Secondary endpoints are recurrence-free survival, time to first subsequent anticancer treatment, and treatment related complications and toxicity. Exploratory endpoints are time to second subsequent anticancer treatment, health-related quality of life, and cost-effectiveness. The Institutional Review Board of the Netherlands Cancer Institute approved the trial, which is actively enrolling patients since January 2020. Clinical trial information: NCT03772028.
A phase Ib/II study of the CD123-targeting antibody-drug conjugate IMGN632 as monotherapy or in combination with venetoclax and/or azacitidine for patients with CD123-positive acute myeloid leukemia.
Authors: Daver Naval Guastad , Wang Eunice S. , Sweet Kendra L , Montesinos Pau , Erba Harry Paul , DeAngelo Daniel J. , Sloss Callum Mortimer , Wang Jiuzhou , Malcolm Kara E , Zweidler-McKay Patrick A
Published: May 2020

TPS7564

Background: Overexpression of CD123 is characteristic of a number of hematological malignancies, including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). IMGN632 is a CD123-targeting antibody-drug conjugate (ADC) with a novel anti-CD123 antibody coupled to a unique DNA-alkylating payload of the recently developed IGN (indolinobenzodiazepine pseudodimer) class of payloads. In preclinical models of AML, IMGN632 exhibited potent anti-leukemia activity, with a wide therapeutic index. Confirming preclinical expectations, encouraging single-agent activity and favorable tolerability have emerged for IMGN632 in the ongoing Phase I trial in patients with CD123-positive AML (ASH 2019, NCT03386513). Preclinical data from AML xenograft models have demonstrated synergy in IMGN632 combinations with azacitidine and venetoclax (EHA 2019), supporting the exploration of these combinations in AML patients. Methods: This Phase Ib/II study is designed to determine the safety, tolerability, and preliminary anti-leukemia activity of IMGN632 when administered in combination with azacitidine and/or venetoclax to patients with relapsed and frontline CD123-positive AML, and the single-agent activity of IMGN632 in patients with minimal residual disease (MRD)-positive AML after frontline treatment. Study Design: Adult patients with CD123-positive relapsed or refractory AML, who are deemed appropriate for experimental therapy, are eligible to enroll as part of the dose escalation phase. Key exclusion criteria for all regimens include active central nervous system disease, and history of sinusoidal obstruction syndrome/venous occlusive disease of the liver. Three combination regimens are being evaluated: Regimen A, IMGN632 plus azacitidine (632+AZA); Regimen B, IMGN632 plus venetoclax (632+VEN); and Regimen C, IMGN632 plus azacitidine and venetoclax (632+AZA+VEN). For each regimen, a Phase Ib dose escalation cohort will determine the recommended Phase II dose (RP2D) of IMGN632 for the specific combination. This will be followed by a Phase II dose expansion stage to further characterize the safety profile and assess antileukemia activity in frontline or relapsed AML patients, depending on combination regimen. In addition, IMGN632 monotherapy is being explored in expansion cohorts of MRD-positive patients to assess conversion rate from MRD+ to MRD-, in fit and unfit AML subpopulations. Clinical trial information: NCT04086264 .