bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I (safety assessment) of durvalumab (MEDI4736) with focal sensitizing radiotherapy in platinum resistant ovarian, primary peritoneal or fallopian tube epithelial carcinoma.
Authors: Tinker Anna , Lim Peter , Aquino-Parsons Christina , Hoskins Paul , Khalaf Daniel , Lheureux Stephanie , Han Kathy , Liu Mitchell , Lum Julian J 
Published: May 2019

TPS5604 Background: Radiation (RT) of malignant neoplasms can induce immunogenic tumor cell death, alter the tumor micro-environment and enhance recruitment of anti-tumor T cells. Co-administration of focal RT and an immune checkpoint-inhibiting agent may overcome immune-suppressive signals and potentiate systemic responses. A phase I study is underway to assess the safety of RT combined with PD-L1 inhibition in patients with recurrent epithelial ovarian/fallopian tube/peritoneal carcinomas (OV). Methods: Women with platinum resistant epithelial OV, ECOG PS 0/1 and ≤ 2 lines of treatment in the platinum-resistant setting are eligible. 1 lesion evaluable by RECIST criteria (v 1.1) and 2 additional lesions suitable for RT (minimal treatment volume 4cc) are required. Pre- and on-treatment biopsies for correlative studies are mandatory. The primary objectives are to assess the safety and tolerability of the focal RT combined with the immune checkpoint inhibitor, durvalumab (D), as defined by dose-limiting toxicities (DLTs), and to define the maximum tolerated RT dose and treatment schedule. The secondary objectives are to evaluate the clinical activity of focal RT and D [RECIST (v 1.1), GCIG CA-125, and immune-related response criteria], progression free survival and overall survival. D 1500 mg delivered intravenously every 28 days = one cycle. RT to the 2 selected target lesions is delivered 24-36 hours prior to the infusion of D. The RT starting dose-level is 24Gy (in 4 fractions) per lesion (given Days -1, 1 and 28 of Cycle 1 and Day 1 of Cycle 2). A 3+3+3 design will permit more extensive exploration of toxicity if DLTs are observed (Table). Investigator assessed DLTs are defined by CTCAE v. 4.03 and include the following: any grade ≥3 adverse event suspected to be related to D or RT (necrosis or recall reactions at previously irradiated sites, RT induced bowel perforation, any unexpected grade 3 or greater toxicity at the site of RT), any grade ≥2 allergic or autoimmune event that involves vital organ function, and any other grade 3 allergic or autoimmune events that do not resolve to grade 1 before the next scheduled dose of D. Treatment may continue up to 12 months. Enrollment began August 2018. To date, no DLTs have been observed at dose level 1 (n= 3) and enrollment is ongoing. Clinical trial information: NCT03283943. [Table: see text]
NRG GY012: A randomized phase II study comparing single-agent olaparib, single agent cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent or metastatic endometrial cancer.
Authors: Mackay Helen , Rimel Bj , Bender David 
Published: May 2019

TPS5609 Background: The Cancer Genome Atlas and others identified genomic events suggesting that endometrial cancer (EC) should be susceptible to DNA repair inhibition. Mutations in classical homologous recombination genes occur in 22% of EC, ARID1A 41% and PTEN loss occurs in 55% of EC. Data from pre-clinical models suggest poly ADP-ribose polymerase (PARP) inhibitors alone or in combination may be an effective therapeutic strategy in EC (Hansen 2016). Combinations of angiogenic inhibitors and PARP inhibitors have demonstrated synergistic effects and have been well tolerated in other tumor types. This study has been designed to compare 2 experimental arms exploring DNA repair inhibition versus cediranib alone which has previously shown promising activity in GOG 229J (Bender 2015). Methods: This is a multicenter randomized three arm study for patients with recurrent, metastatic or persistent EC. Patients are randomized 1:1:1 to cediranib PO 30 mg OD; olaparib 300 mg PO BID or the combination of cediranib 20 mg PO OD with olaparib 300 mg PO BID. All treatment cycles are 28 days. Primary endpoint is progression free survival (PFS). The study is powered to detect an increase in median PFS from 3.6 (based on cediranib alone) to 7.2 months with 90% power, using a one-sided test with α = 0.05 per comparison. Forty patients will be enrolled per arm, with an interim futility analysis planned. Eligibility includes endometroid, serous, and mixed histology EC; at least 1 prior line of chemotherapy (no more than 2 lines for metastatic disease), prior endocrine or immunotherapy is allowed; ECOG PS ≤ 2; adequate hepatic, bone marrow, coagulation and renal function. Archival tumor tissue and blood samples are being collected for translational studies. The study is open across the NRG network; 24 patients are enrolled to date . Amendments are planned to include additional arms investigating combination strategies targeting DNA repair and angiogenesis. Clinical trial information: 03660826.
A multicenter, randomized, double-blind, placebo-controlled phase III study of anlotinib or placebo in combination with gemcitabine and cisplatin (GP) as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC).
Authors: Yang Yunpeng , Huang Yan , Fang Wenfeng , Ma Yuxiang , Cai Qingqing , Li Zhi-Ming , Zhao Hongyun , Zhao Yuanyuan , Zhou Ting , Hong Shaodong , Zhang Yaxiong , Zhang Li 
Published: May 2019

TPS6089 Background: GP is the standard first-line chemotherapy for R/M NPC. However, the outcome of patients who are refractory to first-line chemotherapy is poor. There remains an unmet need for more effective first-line treatment. Overexpression of vascular endothelial growth factor (VEGF) is common in NPC and the higher expression is related to lower OS. This feature makes NPC potentially suitable for antiangiogenic treatment. Anlotinib is a novel multitarget tyrosine kinase inhibitor that targets VEGFR 1 to 3, fibroblast growth factor receptor 1 to 4, and platelet-derived growth factor receptor α and β. Our phase I study of anlotinib in R/M NPC patients who failed from standard treatment had shown a manageable safety profile and promising antitumor activity with an ORR of 25%. This phase 3 trial aims to compare the efficacy and safety of anlotinib versus placebo in combination with GP in patients with R/M NPC in the first-line setting. Methods: Key eligibility criteria of this study are that the patient has metastatic disease after curative radiotherapy, or is primarily metastatic; has an ECOG PS of 0 or 1; has adequate organ function; and has at least 1 measurable lesion according to RECIST 1.1. Eligible patients will be randomized in a 1:1 ratio to receive intravenous gemcitabine at 1 g/m² on days 1 and 8, cisplatin at 75 mg/m² on day 1, plus anlotinib or placebo 12 mg daily orally on days 1–14 every 3 weeks for a maximum of 6 cycles followed by anlotinib or placebo 12 mg daily on days 1–14 every 3 weeks as maintenance therapy. The primary endpoint is PFS. Secondary endpoints include OS, ORR, quality of life and safety profile. Independent Data Monitoring Committee and Independent Review Committee will be used in this study. We assume that the median PFS will be 10 mos in anlotinib group and 7 mos in placebo group. To detect a 3-month improvement of PFS in anlotinib group at a two-sided significant level of 0.05 and power of 0.8, allowing for a dropout rate of 10%, a total of 336 patients will be enrolled. From August 2018, 58 patients have been enrolled. Clinical trial information: NCT03601975.
Reproductive health in cancer.
Authors: Radeke Erika K , Lee Ju-Whei , Patel Ashlesha , Zaren Howard A. , Fisch Michael Jordan , Wagner Lynne I. 
Published: May 2019

TPS6649 Background: Reproductive health needs of females ages 15 to 55 with cancer are poorly understood and overlooked, despite their importance to patients. Uncertainties regarding fertility and pregnancy are intricate and challenging for a patient and a cancer care team. The goals of reproductive health care may come in conflict with the primary objective of cancer care. However, with appropriate counseling and preventive measures, this conflict can be absolved to unify objectives. The primary objective of this trial is to evaluate the success of the implementation of reproductive health programming among reproductive aged females with cancer. To expand knowledge on this subject, the NCI approved the ECOG-ACRIN EROS trial: Engendering Reproductive Health within Cancer Survivorship, with two ancillary studies: Endocrine Disruption in Cancer Care and Sexuality in the first 5 years after Cancer Diagnosis. Methods: The primary study is a multicenter, cluster randomized control trial, with NCI Community Oncology Research Programs randomized to either the non-intervention arm (usual standard practice related to reproductive health) or the intervention arm (using study-specific training and tools). The accrual goal is 668 patients based on the expectation that the intervention can increase the adoption of appropriate reproductive health management within 3 months from the baseline visit from 50% to 80%, with the first 200 to consent to the endocrine disruption substudy. All patients participate in the sexuality part. Pre-menopausal female patients ages 15 to 55 with an initial diagnosis of any type of cancer who have not initiated treatment of any type are eligible to participate. Patients are asked to complete 2 questionnaires at 8 timepoints regarding their reproductive health interests. Providers are also asked to complete questionnaires regarding their healthcare practice in general as well as specific to patients enrolled in this study. The reproductive health management rate at each time point will be summarized, by arm, with frequency and percentage along with its 95% confidence interval. The comparison between the two arms, using a GEE model, can evaluate the intervention effect. EROS was activated in September 2015. To date, 264 patients have been enrolled to the main study and half of these patients are participating in the endocrine disruption correlative. Outcomes pertaining to management and treatment implementation and modification are the cornerstones of this study. It should inform organizations in cancer care to improve guidelines and to include a reproductive health assessment for all young females with cancer. Clinical trial information: NCT01806129.
Digitally captured step counts for evaluating performance status in advanced cancer patients: A single cohort, prospective trial (Digi-STEPS).
Authors: Gresham Gillian , Hendifar Andrew Eugene , Gong Jun , Asher Arash , Walsh Christine S. , Rimel BJ , Posadas Edwin M. , Diniz Marcio , Herring Maurice , Woubeshet Bethy , Baynes Rachel , Figlin Robert A. , Spiegel Brennan , Freedland Stephen J. 
Published: May 2019

TPS6651 Background: Advanced cancer patients undergo dynamic changes in their functionality and physical activity over the course of their treatment. Monitoring patient function is important because it can inform treatment decisions and allow for timely and appropriate intervention. Current scales that assess patient function, such as the ECOG Performance Status (PS), are limited in their ability to capture the wide range in activity that cancer patients can experience on a daily basis outside of the clinic setting. Given recent technological advances in wearable activity monitors, we can collect real-time, objective information about a patient’s daily activity including steps, stairs, heart rate, sleep, and activity intensity. Thus, the primary objective of this study is to determine whether longitudinal changes in objectively-assessed activity are associated with change in physician-rated ECOG PS. Methods: This is a prospective, single cohort trial being conducted at Cedars-Sinai Medical Center. Stage 3/4 cancer patients who are English or Spanish-speaking, ambulatory (assistive walking devices are allowed) and expected to be seen for treatment or follow-up with their oncologist at least every 8 weeks are eligible for study. Consenting patients will be asked to wear a Fitbit Charge HR continuously for 8 weeks during the study period and for one week prior to the 6 month and 1 year follow-up visits. Primary outcomes are change in average daily step counts and ECOG PS at 8 weeks from baseline. Secondary outcomes include: 1) Change in NIH PROMIS patient-reported outcomes (physical function, pain, sleep, emotional distress, and fatigue), 2) Change in frailty status at 8 weeks, 3) Occurrence of adverse events, and 4) 6-month and 1-year survival outcomes. Baseline assessments include a physical exam, medical history, and frailty assessment. The attending oncologist will rate the patient's ECOG PS at baseline and at the end-of-study visit. Weekly NIH PROMIS questionnaires will be administered online over the 8-week study and again at 6 months and 1 year follow-up. The occurrence of serious cancer-related adverse events, chemotherapy-associated toxicities, and hospitalizations will be documented up to 12 weeks from baseline. Survival will be assessed at 6 months and 1 year. Accrual is ongoing with 20 patients currently enrolled of a target sample size of 60 patients. Clinical trial information: NCT03757182.
Lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with advanced melanoma previously exposed to anti–PD-1/PD-L1 agents: Phase 2 LEAP-004 study.
Authors: Arance Fernandez ANA Maria , Ascierto Paolo Antonio , Carlino Matteo S. , Daud Adil , Eggermont Alexander M. , Hauschild Axel , Kluger Harriet M. , Taylor Matthew H. , Smith Alan , Chen Ke , Krepler Clemens , Diede Scott J. , O'Day Steven 
Published: May 2019

TPS9594 Background: Pembro, a PD-1 inhibitor, has shown effective antitumor activity, deep and durable responses, and survival benefit in treatment-naive pts and those with previously treated metastatic melanoma. Len, a potent inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, combined with a PD-1 inhibitor showed antitumor activity superior to either agent alone in preclinical models of colorectal and lung cancer. Additionally, len plus pembro showed anti-tumor activity and was well-tolerated (24-wk ORR, 47.6%; TRAE: gr 3/4, 67%; gr 5, 0%) in pts with advanced melanoma previously treated with 0-2 therapies in the phase 1b/2 KEYNOTE-146 trial. The efficacy and safety of len plus pembro combination therapy will be evaluated in an open-label, phase 2 trial of pts with advanced melanoma that progressed on PD-1/PD-L1 inhibitor therapy (NCT03776136). Methods: Key inclusion criteria: age ≥18 years, histologically/cytologically confirmed unresectable stage III-IV melanoma that progressed (per iRECIST) within 12 weeks of last dose of an approved PD-1/PD-L1 inhibitor therapy (≥2 doses as monotherapy or combined with other therapies), measurable disease, ECOG PS 0/1, no active autoimmune disease, and adequate organ function. Pts must provide a baseline tumor sample. Pts will receive len 20 mg/day orally plus pembro 200 mg IV Q3W for approximately 2 years (35 doses of pembro), after which they may receive len alone until PD or unacceptable toxicity. Response will be assessed per RECIST v1.1 based on blinded independent central review (BICR) Q9W until week 54, Q12W until week 102, and Q24W thereafter. Pts with CR may discontinue treatment after ≥24 weeks of therapy; eligible pts may continue treatment beyond initial RECIST- or iRECIST-defined PD. AEs will be assessed throughout treatment and for 90 days (120 days for serious AEs) after last dose and graded per NCI CTCAE v4.0. Pts will be followed-up for survival status Q12W. The primary efficacy end point is ORR per modified RECIST v1.1 (BICR). Key secondary end points are PFS and DOR per modified RECIST v1.1 (BICR), OS, and safety; an exploratory biomarker analysis is planned. Clinical trial information: NCT03776136.
ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy.
Authors: Butler Marcus O. , Robert Caroline , Negrier Sylvie , In Gino Kim , Walker John WT , Krajsova Ivana , Atkinson Victoria , Hansson Johan , Kapiteijn Ellen , Loquai Carmen , Shaw Heather May , Cheng Tina , Mansard Sandrine , Grob Jean Jacques , Guidoboni Massimo , Mehta Minal , Ascierto Paolo Antonio , Diab Adi 
Published: May 2019

TPS9599 Background: Tilsotolimod (IMO-2125) is a Toll-like receptor (TLR) 9 agonist with potent immunostimulating activity. In an ongoing Phase 1/2 clinical study in patients with advanced melanoma who progressed on or after anti-PD-1 therapy (NCT02644967), intratumoral (IT) tilsotolimod with ipilimumab was well-tolerated, demonstrating durable responses (including complete response > 21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in responders, and an abscopal effect. Methods: ILLUMINATE 301 (NCT03445533) is a randomized phase 3 global, multi-center, open-label study of IT tilsotolimod (8 mg) in combination with ipilimumab (3 mg/kg) versus ipilimumab monotherapy in patients with advanced melanoma and progression on or after anti-PD-1 therapy. Eligible patients are ≥18 years with histologically confirmed unresectable Stage III or Stage IV melanoma, ≥1 measurable lesion accessible for injection (superficial or visceral, the latter with image guidance), ECOG PS ≤1, and adequate organ function. Exclusion criteria include prior TLR agonists, prior ipilimumab (except adjuvant ≥12 weeks before progression), and CNS disease other than stable brain metastases. Patients are randomized 1:1 and stratified by duration of prior anti-PD-1 (≥12 weeks vs <12 weeks), stage (M1c vs other), and BRAF status/prior targeted therapy (TT) (BRAF wildtype vs BRAF mutation+ with TT vs BRAF mutation+ without TT). Primary endpoints are overall response rate (RECIST v1.1) by independent central review and overall survival. Secondary endpoints include durable response rate, time to response, progression-free survival, patient-reported outcomes, and safety. Patients are enrolling at sites in the United States, European Union, Australia, and Canada. References: (1) Haymaker C. Society for Immunotherapy of Cancer Annual Meeting, November 2017, National Harbor, MD; (2) Diab A, et al. European Society of Molecular Oncology Annual Meeting, October 2018, Munich, Germany. Clinical trial information: NCT03445533.
An open label, multicenter, phase II study of KRT-232, an oral small molecule inhibitor of MDM2, for the treatment of patients with Merkel cell carcinoma (MCC) who have failed treatment with anti-PD-1/L1 immunotherapy.
Authors: Hanna Glenn J. , DeCaprio James A. , Mei John Hai Ming , McGreivy Jesse S. 
Published: May 2019

TPS9602 Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a poor prognosis in patients with advanced disease, with mortality as high as 46%. An oncogenic Merkel cell polyomavirus (MCPyV) is present in about 80% of MCC tumors, which inactivates tumor suppressors p53 and RB. Virus-positive MCC has proven to be an immunologically responsive disease and the recently approved PD-L1 inhibitor avelumab (March 2017) has improved the prognosis of patients with advanced MCC. However, despite the addition of immune checkpoint inhibitors to the treatment paradigm, a lack of response or disease progression occurs in up to two-thirds of avelumab patients previously treated with chemotherapy, and 32-44% of first-line patients treated with the PD-1 inhibitors nivolumab or pembrolizumab. KRT-232 is a potent and selective small molecule targeted drug that binds to murine double minute chromosome 2 (MDM2) and inhibits the MDM2/tumor protein 53 (p53) protein-protein interaction. Inactivating mutations in p53 have rarely been found in MCC, and the majority of MCCs with the presence of MCPyV express p53WT. The purpose of this study is to evaluate the tolerability and efficacy of KRT-232 in p53WT MCC patients who have been treated with anti-PD-1/L1 immunotherapy. Methods: The primary objective is ORR by RECIST v1.1 after 2 cycles (42 days) as determined by independent review. A Simon two-stage design is employed. In Stage 1, up to 13 eligible patients will be enrolled and treated with 240 mg KRT-232 once daily (QD) on Days 1-7 of a 21-day cycle. If the predesignated efficacy threshold is reached in Stage 1, enrollment for Stage 2 will include an additional 14 patients (for a total of 27 patients). The study is enrolling in the U.S. Clinical trial information: NCT03787602.
Analgesic Benefit of Pectoral Nerve Block II Blockade for Open Subpectoral Biceps Tenodesis: A Randomized, Prospective, Double-Blinded, Controlled Trial
Authors: Reynolds J. Wells , Henshaw Daryl S. , Jaffe J. Douglas , Dobson Sean W. , Edwards Christopher J. , Turner James D. , Weller Robert S. , Graves Benjamin R. , Freehill Michael T. 
Published: May 2019

BACKGROUND:
Axillary pain is common after arthroscopic shoulder surgery with an open subpectoral biceps tenodesis. We hypothesized that adding a pectoral nerve block II (Pecs II) to an interscalene block (ISB) would improve postoperative analgesia in this surgical population.

METHODS:
Forty patients were enrolled in this prospective, randomized, observer and patient-blinded, single-institution trial. All 40 patients received a single-injection ISB with 20 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The intervention arm (ISB + Pecs II) consisted of 20 patients who also received a Pecs II block using 30 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The 20 control group patients (ISB) received a sham Pecs II block. The primary outcome was postoperative pain scores at 6 hours using the numeric rating scale (NRS; range, 0–10) and was analyzed using the Mann-Whitney U test. Secondary outcomes included the presence of axillary pain at 6 hours, the need for postanesthesia care unit (PACU) opioids, PACU length of stay (LOS) (minutes), NRS pain scores at 24 hours, cumulative opioid usage postdischarge through 24 hours, the presence of nausea or vomiting during the first 24 hours, and Pecs II block duration (in hours, based on time to onset of axillary pain). Data were analyzed using a modified intention-to-treat (ITT) methodology.

RESULTS:
Pain scores (NRS, 0–10) at 6 hours differed significantly between groups: ISB 3.0 (0.25–5.0) (1.7–4.3) versus ISB + Pecs II 0.0 (0–2.0) (0.0–1.1) (median [IQR] [95% CI]); P = .026. Hodges–Lehmann estimator of the difference was 2.0 (95% CI, 0.0–4.0). Fewer patients in the ISB + Pecs II group reported axillary pain at 6 hours and fewer required opioids in the PACU. There were no differences in any of the remaining secondary outcomes.

CONCLUSIONS:
The addition of a Pecs II block to an ISB for patients undergoing arthroscopic shoulder surgery with an open subpectoral biceps tenodesis significantly improved postoperative analgesia and reduced the need for opioids in the PACU.