bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial experience of the adjuvant treatments to the local tumor for metastatic prostate cancer: Assessment of novel treatment algorithms, a multicenter, phase II randomized controlled trial (IP2-ATLANTA).
Authors: Connor Martin John , Shah Taimur T , Sukumar Johanna , Naismith Olivia Frances , Day Emily , Fiorentino Francesca , Falconer Alison , Sarwar Naveed , Gonzalez Michael , Gayadeen Shiva , Jayaprakash Kamalram Thippu , McGrath John , Horan Gail , Heath Catherine , Mangar Stephen , Khoo Vincent , Dudderidge Tim , Staffurth John Nicholas , Winkler Mathias , Ahmed Hashim Uddin ,   IP2-ATLANTA Study Group
Published: May 2020

TPS5600 Background: Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit beyond standard systemic therapy in patients with de novo synchronous metastatic prostate cancer. There is accumulating prospective evidence for local cytoreductive therapy. In particular, the phase III study STAMPEDE which demonstrated improved overall survival in a low burden subgroup of men following cytoreductive radiotherapy. Cytoreductive prostatectomy and minimally invasive ablative therapies (MIAT) are now subject to similar trial evaluation. IP2-ATLANTA will evaluate progression-free and overall survival outcomes with the addition of sequential multi-modal local and metastasis-directed treatments in patients with newly diagnosed metastatic prostate cancer compared to standard care alone. Methods: Phase II, multicentre, three-arm randomised controlled trial using a positive comparator arm ( n=918 ). An internal pilot ( n=80) feasibility phase is incorporated. All men with new histologically diagnosed, hormone sensitive, metastatic prostate cancer, within three months of commencing ADT and of PS 0-2 are eligible. Patients are randomised (1:1:1) to: Control (Standard of Care) OR Intervention 1 (Minimally invasive ablative therapy to the prostate +/- pelvic lymph node dissection [PLND]) OR Intervention 2 (prostate radiotherapy +/- lymph nodes OR Radical prostatectomy +/- PLND). Metastatic burden pre-specified by CHAARTED definition. Men with low-burden disease in intervention arms are eligible for metastasis-directed therapy (stereotactic ablative radiotherapy [SABR] or surgery). Standard systemic therapy given in all arms (incl. docetaxel). Follow-up: min. 2-years; max. 4 years. Primary outcome: progression-free survival (PFS). Secondary outcomes: Overall survival; urinary, sexual & rectal side-effects; patient reported outcome measures. HRA ethical approval (Ref: 19/WA0005). To date, 28/80 (35%) patients have been recruited and randomised across 9 open sites in the internal pilot. Median recruitment rate is 85.7% (IQR 55–86). Internal pilot recruitment expected to be complete by April 2020. IP2-ATLANTA addresses an important research gap in the role of local and metastasis-directed therapy in men with newly diagnosed metastatic prostate cancer. Clinical trial information: NCT03763253 .
RTOG 3506 (STEEL): A study of salvage radiotherapy with or without enzalutamide in recurrent prostate cancer following surgery.
Authors: Posadas Edwin Melencio , Gay Hiram Alberto , Pugh Stephanie L. , Morgan Todd Matthew , Yu James B. , Lechpammer Stanislav , Feng Felix Y 
Published: May 2020

TPS5601 Background: Salvage radiotherapy (SRT) is an important intervention for men with prostate cancer (PCa) who experience biochemical recurrence (BCR) after radical prostatectomy (RP). These patients are in need of cure or else they will develop metastatic disease. NRG/RTOG 9601 (WU Shipley, N Eng J Med 2017) identified a survival benefit from the addition of androgen receptor (AR) inhibition to SRT that was most prominent in men with high-risk features. Enzalutamide (Enza) is a non-steroidal anti-androgen that improves survival in castration-resistant and -sensitive PCa. We hypothesized that enhanced AR suppression with Enza would augment the benefit of SRT + androgen deprivation therapy (ADT) in BCR with high risk features. Methods: RTOG 3506 (STEEL, NCT03809000) is a randomized phase II study of SRT in BCR after RP with a serum PSA ≥ 0.2 ng/mL active in the USA and Canada. Patients are stratified by number of high-risk features including Gleason score (8-10), locoregional node involvement at RP, seminal vesicle invasion, persistently elevated PSA after RP, and PSA > 0.7 ng/mL. All patients receive SRT with 2 years of ADT. The experimental arm also receives Enza 160 mg daily for 2 years. Patients are followed by PSA every 3 months. SRT can be highly individualized per treating physician beyond the mandatory treatment of the prostatic fossa. Treatment of the pelvis and/or para-aortic nodes, as well as sequential or concurrent boosts to a prostatic fossa mass and/or suspicious lymph nodes, are allowed options. This permits individualization of radiotherapy guided by CT, MRI, PET, and/or biopsy findings. The primary goal of this study is to determine whether SRT enhanced ADT with Enza, will improve progression-free survival (PFS) compared to SRT with standard ADT. PFS defined as the first occurrence of biochemical failure, clinical failure, or initiation of new anticancer treatment. STEEL is designed to demonstrate a 35% reduction in the risk of progression at 5 years. An accrual goal of 242 patients will provide 80% power with a one-sided alpha = 0.10. Secondary endpoints include disease control rates, acute and late physician- and patient-reported toxicity, and quality of life. This study was activated in February 2019. Site recruitment and activation are underway. Conclusions: There is an unmet and urgent need for individualized strategies to optimize systemic therapy used with SRT for men with BCR. Outcomes from this study will further clarify the approach to systemic therapy for SRT in high-risk BCR patients. Support: Provided by Pfizer. Clinical trial information: NCT03809000 .
Randomized, phase II trial to evaluate the efficacy and safety of atezolizumab plus capecitabine adjuvant therapy compared to capecitabine monotherapy for triple receptor-negative breast cancer (TNBC) with residual invasive cancer after neoadjuvant chemotherapy (MIRINAE trial, KCSG-BR18-21).
Authors: Park In Hae , Kim Gun Min , Kim Jee Hyun , Kim Hanjo , Park Kyong Hwa , Park Yeon Hee , Baek Sun Kyung , Sim Sung Hoon , Ahn Hee Kyung , Lee Gyeong-Won , Lee Kyoung Eun , Lee Ji Eun , Lim Seungtaek , Jung Kyung Hae , Im Seock-Ah 
Published: May 2020

TPS597 Background: Triple negative breast cancer (TNBC), lack of ER, PR and HER2 expression, is known to have aggressive clinical features such as early recurrence, drug resistance, and frequent distant metastasis at the diagnosis. The most effective chemotherapy combinations used for early TNBC include anthracycline, taxanes, and/or platinum agents. Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) provides important prognostic information and is considered as a surrogate endpoint in many clinical trials especially with TNBC. Patients with residual invasive disease after NAC have a high risk for early relapse and worse prognosis compared to those with pCR. Therefore, patients who did not get pCR could be better candidates for additional adjuvant treatment because their risk of recurrence would be higher than those with pCR. The CREATE-X (capecitabine for residual cancer as adjuvant therapy) trial howed that adjuvant capecitabine treatment improved 5-yr rate of disease free survival in TNBC subtype. A recent study indicated that immunosuppressive microenvironment had developed even in early stage of TNBC with increased T cells with a high exhaustion signature which are targets of immune modulating agents. Therefore, earlier cooperation of immune modulating drugs would be beneficial by generating a long-lasting anti-tumor immune response to micrometastatic disease, thus preventing disease relapse or recurrence. Methods: This study is a phase II, multicenter, randomized open label trial of atezolizumab (anti-PD-L1 antibody) and capecitabine compared with capecitabine in patients with TNBC who had residual disease after NAC. 284 patients will be enrolled from 15 sites in Korea with a primary objective to access the 5-yr invasive disease-free survival (IDFS) rate. Secondary objectives include 5-yr IDFS rate in PD-L1 positive population, distant relapse free survival (DRFS), overall survival (OS), and safety. Major inclusion and exclusion criteria are followings; 1) histologically confirmed TNBC, 2) received anthracycline and taxane based NAC followed by complete breast surgery, 3) residual disease after NAC must be ≥1cm in the greatest dimension, and/or have macroscopically positive lymph nodes. The study is open with 13 patients enrolled at the time of submission. Clinical trial information: NCT03756298 .
Phase III randomized study of adjuvant treatment with the ANTI-PD-L1 antibody avelumab for high-risk triple negative breast cancer patients: The A-BRAVE trial.
Authors: Conte Pier Franco , Dieci Maria Vittoria , Bisagni Giancarlo , De Laurentiis Michelino , Tondini Carlo Alberto , Schmid Peter , De Salvo Gian Luca , Moratello Giacomo , Guarneri Valentina 
Published: May 2020

TPS598 Background: Chemotherapy represents, today, the only treatment option for triple negative breast cancer (TNBC) and still a considerable proportion of pts with primary TNBC experience disease relapse. The risk is particularly high in the presence of poor prognostic features, such as more advanced stage and, for pts treated with neoadjuvant chemotherapy, failure to achieve a pCR. Recent evidence suggest that immunotherapy can play a major role in TNBC pts. Methods: The A-BRAVE trial is an investigator-driven trial sponsored by the University of Padova (Dept. of Surgery, Oncology and Gastroenterology). This is a phase III, multicentric, randomized adjuvant study that compares 1 year of treatment with the anti PD-L1 avelumab vs observation for pts who completed treatment with radical intent for primary TNBC including surgery and chemotherapy. The study enrolls pts in two strata: -Stratum A: primary TNBC pts who completed surgery followed by adjuvant, defined according to one of the following stage categories: if pN2, any pT; if pN1, pT > 2 cm; if pN0, pT > 5 cm. -Stratum B: primary TNBC pts who completed neoadjuvant chemotherapy followed by surgery who did not achieve pCR. Pts who also received additional adjuvant chemotherapy for no more than 6 months are eligible in Stratum B, after the completion of the adjuvant chemotherapy. Pts are randomized (1:1, balanced for strata A and B) to receive Avelumab 10 mg/kg I.V. q2w for 1 year or to observation. The first and second co-primary endpoints are disease-free survival (DFS) in all pts and DFS in Stratum B pts. With a planned sample size of n = 474 pts the trial has 90% power to detect a HR = 0.60 for the first co-primary endpoint (n = 172 events required). Taking into account that the percentage of patients enrolled in the stratum B could range from 70 to 80%, there will be 70-79% power to detect a HR = 0.60 at alpha allocated in this patient subgroup (second co-primary endpoint). Secondary objectives include: DFS in PD-L1 positive pts, overall survival, safety, biomarkers. Tumor tissue, plasma samples and fecal samples are collected for biomarker analysis. The study is currently recruiting across 73 sites in Italy and UK. As of February 2020, n = 349 pts have been enrolled. EUDRACT 2016‐000189‐45. The authors present the A-BRAVE trial in progress on behalf of Italian and UK investigators. Clinical trial information: NCT02926196 .
ABC trial (A011502): A randomized phase III double-blinded placebo-controlled trial of aspirin as adjuvant therapy breast cancer.
Authors: Chen Wendy Y. , Winer Eric P. , Ballman Karla V. , Partridge Ann H. , Carey Lisa A. , Carvan Margaret , Matyka Carol , Openshaw Thomas H. , Visvanathan Kala , Symington Banu , Holmes Michelle D. 
Published: May 2020

TPS600 Background: In-vitro and in-vivo evidence suggest that aspirin may have an anti-tumor effect. Multiple epidemiologic studies have reported improved breast cancer survival among regular aspirin users compared to non-users. Pooled data from randomized trials of aspirin for cardiovascular disease have also reported a decreased risk of metastatic cancer among aspirin users. However, the exact benefits and risks for breast cancer survivors need to be confirmed in a randomized controlled trial. Even if the clinical effect were modest, the global impact would be substantial since aspirin is inexpensive and widely available. Methods: The primary objective is to compare the effect of 300 mg daily aspirin versus placebo upon invasive disease-free survival (iDFS) in high risk HER2 negative breast cancer patients. Secondary objectives include effects on overall survival, cardiovascular disease, toxicity, and adherence. A biospecimen repository will be created for correlative analyses including tumor collection at baseline and blood and urine samples and questionnaires assessing lifestyle factors associated with inflammation (pain, sleep, stress, and depression) at baseline and 2 years. Study design: Subjects will be randomized (1:1) to aspirin 300 mg vs placebo daily for 5 years in a double-blinded fashion. Stratification factors include hormone receptor (HR) status (positive vs negative), body mass index ( < or ≥ 30 kg/m2), and stage (II vs III). Subjects will be followed every 6 six months while on study drug, then annually for 10 years. Accrual goal is 2936 patients to reach 381 iDFS events. We have 80% power to detect HR 0.75 assuming 5-year iDFS on placebo of 77%. Eligibility: Eligible subjects include patients aged 18-70 diagnosed with a primary invasive HER2 negative breast cancer. If HR positive, tumors need to be node positive and diagnosed within the past 10 years. If HR negative, tumor can be node positive or T2-4N0 within 18 months of diagnosis. Subjects who are currently anticoagulated or those with a prior history of GI bleeding, atrial fibrillation, or myocardial infarction are excluded. Subjects who regularly use aspirin (defined as ≥ 5 days per week) need to stop 30 days prior to enrollment. Updated accrual numbers will be given at the time of presentation. Clinical trial information: NCT02927249 .
A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy (CCRT) for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082).
Authors: Furusawa Akiko , Takekuma Munetaka , Usami Tomoka , Kondo Eiji , Nishio Shin , Nishino Koji , Miyamoto Yuichiro , Yoshimura Ryoichi , Watanabe Miho , Mikami Mikio , Enomoto Takayuki 
Published: May 2020

TPS6094 Background: Cervical cancer is one of the common gynecologic cancer and the incidence of invasive cervical cancer has increased over the past few decades, particularly in younger women. The standard treatment for stage IB to IIB cervical cancer is a radical hysterectomy. In Japan, more than 80% of institutions, radical hysterectomy is chosen as the primary treatment for patients with stage IB1 and IIA1 cervical cancer. Patients with high-risk factors would be recommend adjuvant concurrent chemoradiotherapy (CCRT). However, adjuvant CCRT might not reduce distant metastasis and might cause of severe gastrointestinal and urinal toxicity. To avoid those adverse events of adjuvant CCRT, many Japanese gynecologic oncologists perform chemotherapy as adjuvant therapy. In the first multi-institutional phase II trial conducted in stage IB-IIA cervical cancer with pelvic lymph node metastasis (JGOG1067), we found a 5-years disease free-survival rate of 86.5%, suggesting the adjuvant chemotherapy had promising efficacy and would be feasible for a long time. No prospective study reported that adjuvant chemotherapy would improve overall survival in patients with the high-risk cervical cancer. Methods: High risk stage IB-IIB cervical cancer patients who underwent radical hysterectomy are eligible for the study. Patients with high risk are defined as those with pelvic lymph-node metastasis and/or parametrial invasion. Patents with SCC, adenocarcinoma, adenosquamous cell carcinoma are eligible for the study. After providing informed consent, patients are randomized on a 1:1 basis to receive CCRT or chemotherapy. Randomization is stratified by the faculty, FIGO stage, and pathological subtype (SCC or non-SCC). Treatment have to be started within 6 weeks after surgery. CCRT group is given whole pelvis irradiation 50.4Gy and cisplatin (40mg/m2/week). Chemotherapy group is given paclitaxel (175mg/m2) plus cisplatin (50mg/m2) or paclitaxel (175mg/m2) plus carboplatin(AUC of 6). The primary endpoint is overall survival (OS). Secondary endpoints are disease free survival (DFS), adverse events and QOL. This study began in November 2019 and a total of 290 patients will be accrued within 5 years. The study is coordinated by of the JGOG cervical cancer committee. Clinical trial information: 041190042.
Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Arend Rebecca Christian , Monk Bradley J. , Burger Robert Allen , Herzog Thomas J. , Ledermann Jonathan A. , Moore Kathleen N. , Secord Angeles Alvarez , Shapira Roni , Tewari Krishnansu Sujata , Huang Marilyn , Amit Amnon , Rachmilewitz Minei Tamar , Harats Dror , Penson Richard T. 
Published: May 2020

TPS6097 Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism: a broad antiangiogenic effect and induction of a tumor directed viral immune response. In a phase II trial in platinum resistant ovarian cancer VB-111 in combination with weekly paclitaxel showed a CA-125 response rate (RR) of 58% and median overall survival (OS) of 498 days compared to 172.5 days in the sub-therapeutic dose (p = 0.028). The combination treatment was well tolerated. Favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III randomized controlled trial, VB-111-701/GOG-3018 (OVAL) was initiated in collaboration with the GOG Foundation, Inc. Methods: The OVAL study, NCT03398655, is an international, randomized, double-blind, placebo-controlled, phase III study. Patients with recurrent platinum-resistant epithelial ovarian cancer, who have measurable disease (RECIST 1.1) and were previously treated with up to 5 lines are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. Treatment beyond asymptomatic RECIST progression may continue until progression is confirmed by follow up imaging. The primary endpoints are OS, safety and tolerability. Secondary endpoints include progression free survival, and objective RR by CA-125 (per GCIG criteria) and RECIST 1.1. The sample size calculation of 400 patients (event driven) provides 92% power to detect a difference in survival at the two-sided 5% significance level using the logrank test. A pre-planned interim analysis will take place in Q1 2020 to assess whether the CA-125 RR per GCIG criteria in the treatment arm is sufficiently larger than in the control arm and is comparable to the positive results of the phase II study. Study enrolment is ongoing and over 80 patients were enrolled in the US and Israel. Enrollment expansion to Europe is planned in 2020. Clinical trial information: NCT03398655.
ENGOT-OV44/FIRST study: a randomized, double-blind, adaptive, phase III study of standard of care (SOC) platinum-based therapy ± dostarlimab followed by niraparib ± dostarlimab maintenance as first-line (1L) treatment of stage 3 or 4 ovarian cancer (OC).
Authors: Hardy-Bessard Anne-Claire , Moore Kathleen N. , Mirza Mansoor Raza , Asselain Bernard , Redondo Andres , Pfisterer Jacobus , Pignata Sandro , Provencher Diane M. , Cibula David , Reyners Anna K.L. , Bodnar Lubomir , Glasspool Rosalind , Papadimitriou Christos , Eitan Rami , Han Sileny N. , Duska Linda R. , Rimel BJ , Divya Gupta , Chen Jian , Pujade-Lauraine Eric 
Published: May 2020

TPS6101 Background: Despite surgery and CT (paclitaxel + carboplatin ± bevacizumab [bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3 or 4 OC. Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor that has recently demonstrated efficacy in 1L therapy. Dostarlimab (TSR-042) is an anti-programmed death (PD)-1 humanized monoclonal antibody that has shown clinical activity as monotherapy in early phase trials. The currently enrolling ENGOT-OV44/FIRST study will compare efficacy and safety of CT + dostarlimab + niraparib ± bev (Arm 3) vs CT + niraparib ± bev (Arm 2). Methods: Eligible pts are ≥18 years of age, with FIGO stage 3 or 4 non-mucinous epithelial OC, ECOG performance status < 2, and tumor tissue available for PD-1 ligand (PD-L1) testing. After cycle 1 of CT, pts are stratified by concurrent bev use, BRCA mutation/homologous recombination repair status, and disease burden, then randomized 1:2 into trial Arms 2 and 3 (Table). Dostarlimab is administered at 500 mg IV Q3W during the CT period, then 1000 mg IV Q6W during the maintenance period. Niraparib dosing is 200 mg PO QD for pts with baseline bodyweight (BW) < 77 kg and/or platelet count (PC) < 150,000/µL, or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/µL. The dual primary endpoints are PFS, based on investigator assessment per RECIST v1.1, in both PD-L1+ and all patients. Initially the study enrolled pts to Arm 1. This arm was discontinued following positive results from the PRIMA/ENGOT-OV26/GOG-3012 and PAOLA-1/ENGOT-OV25 studies. This allows investigators to offer the current standard of care to all patients. Clinical trial information: NCT03602859, EUDRACT 2018-000413-20. [Table: see text]