bluuebunny/crossref_metadata_2025_split huggingface dataset:
A randomized phase II study comparing single-agent olaparib, single-agent cediranib, and the combinations of cediranib/olaparib, olaparib/durvalumab (MEDI4736), cediranib/durvalumab (MEDI4736), and olaparib/AZD5363 (capivasertib) in women with recurrent, persistent, or metastatic endometrial cancer.
Authors: Rimel B.J. , Bender David , Enserro Danielle , Westin Shannon Neville , Richardson Debra L. , Holman Laura L. , Alluri Nitya , Stuckey Ashley , Garg Ruchi , Gill Sarah , Tanner Edward , Leath Charles A. , Backes Floor Jenniskens , Fleury Aimee , Mackay Helen 
Published: June 2023

TPS5629 Background: Identifying new approaches for the treatment of advanced endometrial cancer (EC) is a priority. A platform study design allows for a faster investigation of novel drug combinations. NRG-GY012 is an ongoing platform study investigating drug combinations with the PARP inhibitor olaparib (O) and the anti-angiogenic agent cediranib (C). Results from the first set of arms established improved PFS for combination cediranib/olaparib over C alone, but did not meet its prespecified statistical significance. In this second set of arms, based on preclinical data, we are investigating the combination of O with an AKT inhibitor (capivasertib), O with durvalumab and C with durvalumab compared to the reference arm of C alone. Methods: This is a multicenter randomized four arm study for patients with recurrent, metastatic or persistent EC. Patients are randomized 1:1:1:1 to cediranib PO 30 mg Daily; olaparib 300 mg PO BID and capivasertib 400mg 4 day on/3 off schedule; olaparib 300 mg PO BID and durvalumab 1500mg q28 days; or the combination of cediranib 20 mg PO Daily 5 days on/2 days and durvalumab 1500mg q28. All treatment cycles are 28 days. Primary endpoint is progression free survival (PFS). The study is powered to detect a doubling 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 at 50% information time. 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 alone is allowed; prior treatment with lenvatinib and pembrolizumab is excluded. Archival tumor tissue and blood samples are being collected for translational studies. The study is open across the NRG network; 76 of a planned 168 patients are enrolled to date. Safety analysis at the time of 36 patients enrolled did not demonstrate any new safety signals and the study was approved to continue enrollment. Clinical trial information: NCT03660826 .
Randomized phase III trial in MMR deficient (MMRd) endometrial cancer (EC) patients comparing chemotherapy (CT) alone versus dostarlimab in first line advanced/metastatic setting: DOMENICA study (GINECO-EN105b/ENGOT-en13 study).
Authors: Joly Florence , Ray-Coquard Isabelle Laure , Rubio Maria Jesus , Paoletti Xavier , Davis Alison J. , Hudson Emma , Lorusso Domenica , Tognon Germana , Hasler-Strub Ursula , Choi Chel Hun , Vardar Mehmet Ali , Lheureux Stephanie , Van Gorp Toon , Tan David Shao Peng , Trillsch Fabian , Eberst Lauriane , Lescure Céline , Hardy-Bessard Anne-Claire , Chaix Marie 
Published: June 2023

TPS5630 Background: The standard treatment for advanced EC is still platinum-based combination CT, regardless of the histology, molecular status and the patient’s profile. However, EC patients are a particularly frail group of patients, often with co-morbidities. Tolerance of CT can be difficult and induce long-term toxicities. In advanced EC disease, MMRd/MSI-H tumors represent 15 to 20 % of cases. Preclinical data suggest that these tumors are more resistant to platinum. On the other hand, anti-PD1 immunotherapy has shown impressive results among MMRd/MSI-H EC patients after platinum-based CT. The aim of this study is to de-escalade the first line advanced/metastatic treatment of patients with MMRd/MSI-H endometrial cancer with the objective to avoid carboplatin-paclitaxel related toxicities by substituting CT with the PD1 inhibitor dostarlimab. Methods: DOMENICA is an ongoing international randomized, open-label, phase III trial. 142 patients with MMRd/MSI-H EC Stage III or Stage IV or first recurrent disease without curative treatment (surgery, radiation therapy, +/- adjuvant CT) will be randomized (1:1) to receive either 4 cycles of dostarlimab 500mg every 3 weeks followed by dostarlimab 1000mg every 6 weeks as maintenance up to 2 years or 6 cycles of carboplatin-paclitaxel. A cross over is allowed from the CT arm to the dostarlimab arm at first progression. The maximum treatment duration with dostarlimab will be 24 months. Stratification factors are prior adjuvant CT, prior pelvic radiotherapy. The primary endpoint is the progression-free survival (PFS). Secondary endpoints include overall survival (OS), PFS2, quality of life, best objective response rate, disease control rate, duration of response rate, safety, tolerability, time to first and second subsequent therapy, efficacy of second systemic therapies, pharmacokinetics description and immunogenicity determination. The study is designed to expect a 17.8-months PFS in dostarlimab arm and a 10-months PFS in the CT arm, translating to a hazard ratio of 0.58. A protocol amendment is submitted to increase patient population (with extended eligibility criteria, PFS hypothesis). Status: The DOMENICA/GINECO-EN105b/ENGOT-en13 trial is currently recruiting, the first patient was randomized in April 2022. Clinical trial information: NCT05201547 .
GCIG SB-001/NSGO-CTU-PEACE/ANZGOG 1923/2020: Palliation in gynae-oncology—Patients' expectations and assessment of care.
Authors: Lindemann Kristina , Liland Heidi , Donner Mia Sejer , Brew Sue , Lee Yeh Chen , Vistad Ingvild , Berge Nilsen Elisabeth , Lombard Janine Margaret , Mirza Mansoor Raza , Madsen Kristine , Hansson Anne Marie , Andrews John , Campbell Rachel , Davis Alison J. 
Published: June 2023

TPS5635 Background: Patients with advanced gynaecological cancers who are approaching end of life (EOL) have a high symptom burden and following several prior lines of therapy, a low likelihood of response to further anti-cancer treatment. Despite this, 20-30% of women with gynecological cancer received chemotherapy in the last 30 days of life, with potentially detrimental effects on health and quality of life. Little is known about patients' and carers' perceptions and preferences in this phase of illness. Eliciting patient’s values and preferences for EOL care and shared decision-making are central elements of GCIG SB-001/NSGO-CTU-PEACE with the aim of improving patient-centered EOL care. The primary aim of PEACE is to assess the feasibility of collecting data on patient satisfaction towards EOL. Secondary aims include collecting data on patient and carer satisfaction with care, as well as prospective collection of details of their care. Methods: PEACE will prospectively enroll patients in Norway and Australia. Key eligibility criteria include: Patients with gynaecological cancer at an advanced stage with a predicted life expectancy of approximately 4 months. Patients may be on anti-cancer treatment or may be under observation/palliative care. In addition, the patient must be able (both physically and cognitively) to complete patient-reported outcome measures independently. The study will also include an appointed carer (not mandatory). Patient and carer satisfaction with care and the importance of domains of care will be assessed with the CANHELP-Lite individualized (Canadian Health Care Evaluation Project) instrument and FACIT (Functional Assessment of Chronic Illness Therapy). Carer’s perception of the bereavement period and the quality of the patient’s death will be assessed with the CANHELP lite bereavement and the Quality of Death and Dying questionnaire. The study will prospectively collect data on EOL treatment. Patient and carer satisfaction with care and quality of the dying process will be summarized by standard descriptive statistical measures. A sample size of 65 patients would have at least 80% power with 95% confidence to rule out a 60% completion rate in favour of the more interesting 75% rate. Assuming a 10% drop-out rate, PEACE will enrol 73 patients. Enrolment commenced in December 2022. ClinicalTrials.gov Identifier: NCT05142150 Clinical trial information: NCT05142150 .
KEVLAR: A phase 2b, multi-institutional, randomized, blinded, controlled trial to assess the safety and efficacy of two schedules of RRx-001 vs. standard of care in attenuating severe oral mucositis (SOM) in patients receiving concomitant chemoradiation (CRT) for the treatment of locally advanced squamous cell carcinomas (SCC) of the oral cavity (OC) or oropharynx (OPC).
Authors: Reid Tony R. , Oronsky Bryan , Caroen Scott , Abrouk Nacer , Stirn Meaghan , Sonis Stephen T. 
Published: June 2023

TPS6113 Background: The results of an open-labeled Phase 2a trial suggested that infusion of RRx-001 (bromonitrozidine), a nitrogen-containing NLRP3 inhibitor and Nrf2 activator, attenuated the course and severity of SOM associated CRT (cisplatin/IMRT) in cancers of the mouth or OPC without impeding tumor response. The primary efficacy objectives of KEVLAR are to replicate the findings of the earlier trial and to determine if a higher dose of RRx-001 (8 mg x 4 doses prior to CRT) will favorably impact overall SOM incidence. Methods: KEVLAR is a planned Phase 2b study to be conducted at about thirty sites in North America. Approximately 216 patients with pathologically confirmed SCCs of the OC or OPC will be randomized equally into one of 3 cohorts: Arm 1 will receive RRx-001, 8 mg/dose infusions twice weekly during the 2 weeks prior to CRT start; Arm 2 will receive RRx-001, 4 mg/dose in the same schedule; Arm 3 will receive best supportive care only. All patients will receive intensity modulated radiation therapy (IMRT) in 2.0-2.2 Gy fractions/weekday to a cumulative radiation dose of up to 72 Gy. CRT must include cisplatin administered either weekly (40 mg/m2) or tri-weekly (100 mg/m2). Radiation fields must include at least two oral sites at SOM risk planned to receive at least 55 Gy. Mucositis indicators will be assessed twice weekly by trained evaluators. OM will be scored centrally using WHO criteria from the first day of CRT until resolution of ulcerative OM (WHO grade ≤1). Adverse events will be evaluated using NCICTCv5 criteria. Patients will be followed for 24 months post the last day of radiation and tumor response will be recorded quarterly using RECIST criteria.
IMRT followed by pembrolizumab in the adjuvant setting in anaplastic cancer of the thyroid (IMPAACT): Phase II trial adjuvant pembrolizumab after IMRT in ATC.
Authors: Cabanillas Maria E. , Gunn Gary Brandon , Zafereo Mark E. , Wang Rui Jennifer , Iyer Priyanka C. , Maniakas Anastasios , Spiotto Michael T , Dadu Ramona 
Published: June 2023

TPS6117 Background: Anaplastic thyroid carcinoma (ATC) has historically been an almost uniformly rapidly fatal disease. In patients with loco-regional disease with no distant metastasis (stage IVB), and without a targetable mutation, a combination of external beam radiation delivered via intensity modulated techniques (IMRT) +/- concurrent cytotoxic chemotherapy is the current standard of care. However, the relapse rate is very high within the first year of diagnosis. Our data show that 90% of ATCs express PD-L1, with 43% having expression levels greater than 50%. A clinical trial with an anti-PD1 drug in ATC patients with active disease showed that patients with ATC had a response rate of 19%. Additionally, as tumor PD-L1 expression has been linked to radioresistance and there is a need to target micrometastatic disease, using adjuvant checkpoint inhibitor is a rational strategy in these patients. Methods: This is an open label, single center, phase 2 trial of adjuvant pembrolizumab after external beam radiation to the primary tumor in patients with stage IVB ATC. The primary cohorts will include those with gross, locoregional disease who have completed treatment with IMRT +/- concurrent radiosensitizing chemotherapy. Patients will be treated with adjuvant pembrolizumab (400mg IV Q6 weeks for up to 9 cycles), 2-6 weeks after completion of radiation. Patients will be enrolled based on dose of radiation in cohort 1 (high dose group, > 51 Gy), cohort 2 (palliative dose group, < 50 Gy). Cohort 3, consisting of those who underwent surgery followed by IMRT plus concurrent chemotherapy will be an exploratory cohort. Restaging scans will be performed every 12 weeks after enrollment. MRI brain will be repeated every 6 months in the absence of evidence of progression. The primary endpoint is median PFS (from the start of adjuvant pembrolizumab) in cohorts 1 and 2. Secondary endpoint is median overall survival in cohorts 1 and 2. Cohort 3 (5 patients) will have an exploratory endpoint, to estimate the median disease-free survival (DFS). Statistics: Survival analyses will be performed using the Kaplan-Meier method. Based on historical data, the median PFS for unresected patients is 6.8 months. For an expected improvement of median PFS by 3.7 months, with a combined total of 30 evaluable patients in cohorts 1 and 2, we anticipate having 80.0% power using 1-sided 10% alpha for a one-sample log rank test. The trial began enrollment in July 2022. This trial is sponsored by philanthropic funds and Merck. ClinicalTrials.gov ID NCT05059470. Clinical trial information: NCT05059470 .
A phase II single-arm, open-label trial of T-DM1 (ado-trastuzumab emtansine) and neratinib for HER2-positive breast cancer with molecular residual disease (KAN-HER2 MRD).
Authors: Elliott Mitchell , Fuentes Antrás Jesús , Echelard Philippe , Meti Nicholas , Nguyen Alisa , Liu Michelle , Sanabria Salas Carolina , Smith Christopher Gareth , Rushton Moira Katherine , Siu Lillian L. , Berman Hal K. , Bedard Philippe L. , Cescon David W. 
Published: June 2023

TPS620 Background: HER2-positive breast cancer is a biologically and clinically aggressive subtype that has historically been associated with poor outcomes, but for which there are now multiple effective targeted therapies. Patients who have residual disease following standard neoadjuvant therapy have an elevated risk of metastatic recurrence. In addition, the detection of circulating tumor DNA (ctDNA) in the adjuvant period is strongly associated with relapse and can further stratify patients with residual disease. The ctDNA-based detection of molecular residual disease (MRD) is an emerging strategy to identify patients for treatment intensification, and may enable the development of novel curative treatment strategies for “recurrence interception”. Preclinical and clinical evidence support the investigation of neratinib, an irreversible inhibitor of the HER2 tyrosine kinase, in combination with standard T-DM1 in the adjuvant setting for patients with HER2-positive breast cancer and evidence of MRD. Methods: KAN-HER2 MRD is a multicentre, investigator-initiated, open label, single arm phase II trial to evaluate the addition of neratinib to standard T-DM1 in patients with detected MRD. Participants with HER2-positive breast cancer and residual disease following neoadjuvant therapy are pre-screened (Part A) for MRD using a tumor-informed assay (NeoGenomics RaDaR). Those with ctDNA detected following 2-6 cycles of adjuvant T-DM1 will proceed to the interventional phase (Part B) where neratinib is added to standard T-DM1 at the previously-determined recommended phase 2 combination dose of 160 mg/day, in continuous cycles. The primary endpoint is the rate of ctDNA clearance at 12 weeks after treatment initiation (ctDNAwk12); the study is designed with a 2-stage approach and has sufficient power to detect a clearance rate of 40%. Secondary endpoints include MRD rates and their clinical correlates, invasive disease free survival (iDFS), and safety. Bio-specimens including diagnostic biopsies, residual disease, and peripheral blood are being collected from all participants for additional correlative studies. Enrolment in Part A was initiated at the first trial site (Princess Margaret Cancer Centre) in December 2022. KAN-HER2 represents the first reported MRD-directed interception trial for HER2-positive breast cancer. Clinical trial information: NCT05388149 .
FLEX, a real-world evidence full transcriptome study of 30,000 patients with early-stage breast cancer.
Authors: Brown Eric Allen , Gold Linsey P. , Gray Carl R. , Marks Douglas Kanter , Thomas Vibha Taneja , Santillan Alfredo A. , Singleton Ciera S , Audeh M. William William ,   FLEX Investigators Group
Published: June 2023

TPS621 Background: Clinical trials have been an invaluable tool in providing improvements in the discovery, treatment, and quality of life for various diseases and disorders including breast cancer, which impacts millions of people each year. Historically, patient trial populations have not been racially diverse due to several factors such as bias, healthcare distrust, access, and eligibility criteria. However, current efforts are focused on improving diversity and inclusion to promote efficacy and health equity across all races/ethnicities. The ongoing, multi-center FLEX trial (NCT03053193), which pairs clinical data and full transcriptome expression data, seeks to enroll 30,000 patients to accelerate real world research. Due to the size of the database, it is also expected to capture patients typically underrepresented in clinical trials. Methods: FLEX is the first of its kind, prospective, observational trial that enrolls patients who are ≥ 18 years old with histologically proven stage I-III breast cancer with up to 3 positive lymph nodes. Patient eligibility for study enrollment include standard of care MammaPrint testing with or without BluePrint and consent to clinically annotated full transcriptome data collection. The study infrastructure facilitates the generation of hypotheses for targeted sub-studies. The FLEX network fosters collaboration with 114 sites, including one site in Greece and Israel, encouraging participating investigators to initiate sub-studies that can address research questions that are important for breast cancer management. All proposed sub-studies are vetted and approved by Research and Scientific Review Committees. Since launching in April 2017, 12,569 patients have been enrolled including those who have been historically underrepresented in trials (African American n= 1025; Latin n= 341; Asian n=156). Forty-two investigator initiated sub-studies have been approved and are in progress, with 40 abstracts accepted in national and international congresses. Five ongoing sub-studies within FLEX address differences in underlying biology and treatment response/management among African American, Latina, and Asian American patients with early-stage breast cancer. These studies provide a broader understanding of how differential gene expression patterns unique to racial/ethnic groups can impact treatment outcomes. With the large FLEX database, enrollment and sub-studies are extended to other racial/ethnic groups that are underrepresented in clinical trials, but not limited to specific groups. Overall, the FLEX study strives to use full transcriptome data to improve precision medicine in early-stage breast cancer. Clinical trial information: NCT03053193 .
MELODY (Methods for Localization of Different Types of Breast Lesions): A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).
Authors: Banys-Paluchowski Maggie , Kühn Thorsten , Masannat Yazan , Rubio Isabel T. , de Boniface Jana , Ditsch Nina , Karakatsanis Andreas , Dave Rajiv V , Potter Shelley , Kothari Ashutosh , Gentilini Oreste Davide , Weber Walter Paul , Krawczyk Natalia , Hartmann Steffi , Karadeniz Cakmak Guldeniz , Hahn Markus , Lux Michael Patrick , Smidt Marjolein , Cabioglu Neslihan , Harvey James ,   MELODY Study Group
Published: June 2023

TPS626 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com ). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 20 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Clinical trial information: NCT05559411 .