bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCF-001 TRACK (Target Rare Cancer Knowledge): A national patient-centric precision oncology trial for rare cancers.
Authors: Subbiah Vivek , Groisberg Roman , Skefos Catherine , Cleary James M. , Subbiah Ishwaria Mohan , Palma Jim , Oster Mary , Young Steven W. , Elvin Julia Andrea , Sicklick Jason K. , Gaffey Sarah , Ward Ashley , Alexander Brian Michael , Lee J. Jack , De Pradip , Kato Shumei , Kurzrock Razelle 
Published: June 2021

TPS3143 Background: Many rare cancers are understudied, and affected patients often have few if any standard treatment options and limited access to clinical trials. Comprehensive genomic profiling (CGP) is a robust tool to efficiently identify the genomic alterations of cancer and can be applied to study rare tumors. The promise of this technology is to simultaneously enhance our understanding of diverse rare tumors and find matched therapies to benefit the individual patient in real-time. The COVID19 pandemic has challenged the “trial-centric” clinical trial infrastructure. Novel “patient-centric” trials are needed, especially for rare cancers. TRACK is a decentralized, patient advocacy-initiated trial that aims to establish whether patients with rare tumors and cancer of unknown primary can benefit from matched molecular therapy as dictated by their CGP results. Methods: This is a national open label, non-randomized, multi-center (includes community and academic centers) pragmatic study in rare tumors (<6 cases per 100,000 persons per year) and cancer of unknown primary. All participants will have tumor tissue and blood analyzed by CGP (FoundationOneCDx and FoundationOneLiquidCDx). A Virtual Molecular Tumor Board (VMTB) will convene to identify targeted treatment recommendations for participants with genomic alterations. Overall, 400 participants will be enrolled to achieve the goal of 100 patients matched to genomically informed treatment, utilizing remote consenting to ensure study access regardless of geographic location. The primary feasibility endpoint is the percent of participants who receive a molecularly matched treatment after recommendation from the VMTB. The primary efficacy endpoint is the progression-free survival (PFS) among participants who received the molecularly matched treatment. Secondary endpoints include the percent of participants with genomic alterations, overall response rate, response duration, overall survival, clinical benefit rate (SD > 6 months; PR; CR), and high-grade toxicities (as available) of matched targeted therapy. Exploratory endpoints include matching rates; understanding genomic correlates of response; concordance rates between CGP from tissue and blood, time-to-treatment failure, and the impact of the cancer treatment from the patient perspective (via ESAS-FS, a validated patient-reported outcomes (PRO) instrument). All eligible and enrolled patients, regardless of whether receiving matched treatment or not, will be followed for a minimum of one year in a uniform way such that the treatment efficacy and outcomes can be assessed in standard formats. The study is open with six patients enrolled at time of submission. Clinical trial information: NCT04504604.
Total neoadjuvant treatment versus standard chemoradiation to increase the sphincter preservation rate for distal locally advanced rectal cancer (TESS).
Authors: Xiao Weiwei , Wu Xiaojun , Cai Peiqiang , Zhuang YeZhong , Wang Xiaozhong , Bai Shoumin , Wang Qiaoxuan , Ye YiJing , Liu Qing , Liu Min , Liu Shuang , Zeng ZhiFan , Pan Zhi-Zhong , Gao Yuanhong , Chen Gong 
Published: June 2021

TPS3615 Background: Standard treatment of rectal cancer is neoadjuvant capecitabine chemotherapy with radiotherapy, followed by total mesorectal excision (TME). Total neoadjuvant treatment (TNT), a new concept, suggests organ preservation as an alternative to rectal excision in good responders after neoadjuvant chemoradiotherapy to decrease surgical morbidity and increase quality of life. RAPIDO and PRODIGE-23 trials showed that TNT strategy could improve the pathological complete response (pCR) rateand reduce the risk of distant metastasis. The objective of this trial is to increase the proportion of sphincter preservation rate for distal rectal cancer patients by optimizing tumor response, by using TNT regimen as compared to conventional chemoradiotherapy. TESS (clinicalTrials.gov, NCT03840239), a prospective, open label, multicenter, randomized phase 2 study, is underway. Methods: Main inclusion criteria include: cT3-4aNany or cTanyN+ rectal adenocarcinoma aged 18-70y; ECOG performance 0-1; distance≤5cm from anal verge. 168 patients will be randomized 1:1. Patients in the TNT group will receive 2 cycles of neoadjuvant chemotherapy Capeox (capecitabine + oxaliplation) before, during and after radiotherapy 50Gy/25 fractions, before TME (or other treatment decisions, such as watch and wait) and adjuvant chemotherapy capecitabine 2 cycles. Patients in the standard treatment group will receive neoadjuvant radiotherapy 50Gy/25 fractions combined with capecitabine 5 weeks before TME (or other treatment decisions, such as watch and wait), and adjuvant chemotherapy Capeox 6 cycles. Primary endpoint is the rate of sphincter preservation rate (absence of stoma). Secondary endpoints include: Ratio of sphincter preservation strategy; pathological complete response rate and tumor regression grade distribution; acute toxicity; surgical complications; long-term anal function; late toxicity; ECOG standard score; disease-free survival; overall survival. First site opened in January 24, 2019. Clinical trial information: NCT03840239.
A multicenter, randomized phase 1b/2 study of gemcitabine and cisplatin with or without CPI-613 as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-04).
Authors: Sahai Vaibhav , Chang Amy E. , Crysler Oxana V. , Zhen David Bing , Beg Muhammad Shaalan , Pardee Timothy S. , Luther Sanjeev , Griffith Kent A. , Zalupski Mark 
Published: June 2021

TPS4158 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy. Gemcitabine and cisplatin is a standard first-line systemic therapy with an overall response rate (ORR) of 26% and a median overall survival of 11.7 months. This investigator-initiated, multi-institutional phase 1b/2 trial is designed to investigate the role of gemcitabine, cisplatin and CPI-613 in pts with advanced BTC. CPI-613 is a stable intermediate of a lipoate analog that inhibits pyruvate dehydrogenase and a-ketoglutarate dehydrogenase enzymes of the tricarboxylic (TCA) cycle preferentially within the mitochondria of cancer cells. Methods: Key eligibility criteria include histologically confirmed, metastatic or unresectable BTC (intra- or extra-hepatic and gallbladder) without prior systemic treatment, measurable disease per RECIST v1.1, and ECOG PS 0-1. Primary objective of the phase 1b portion (n = 20 pts; TiTE-CRM methodology) is to determine the recommended phase 2 dose of the combination, and for the phase 2 portion, ORR (n = 48-58 pts; 2:1 randomization). Assuming a null hypothesis ORR of 25% and an alternative hypothesis of 43%, this ongoing trial has at least 80% power with a one-sided alpha of 0.05 to identify treatment efficacy of the study arm. Secondary objectives include evaluation of progression-free survival, overall survival, and safety in this patient population. Exploratory objectives include identification of molecular markers of response and resistance in tumor samples and serially collected blood (pre-, on-, and post-therapy), including whole exome/transcriptomic analysis, and immunohistochemical staining (PDK, PDH, KGDH, SOD2 and CD79a). Gemcitabine 1000 mg/m2, cisplatin 25 mg/m2 with or without CPI-613 (dose levels: 500 mg/m2, 1000 mg/m2, 1500 mg/m2, and 2000 mg/m2) will be given IV on days 1 and 8 every 21 days. In the absence of disease progression, pts may continue therapy for up to 2 years. Total accrual goal is 68-78 evaluable pts. To date, 5 of planned 20 pts enrolled on the phase 1b portion are without dose limiting toxicity. Clinical trial information: NCT04203160.
The IMMULAB trial: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC).
Authors: Vogel Arndt , Goetze Thorsten Oliver , Hausner Guido , Geißler Michael , Siegler Gabriele Margareta , Fischer von Weikersthal Ludwig , Kestler Angelika M. R. , Kleiß Matthias , Müller Tobias , Teufel Andreas , Marquardt Jens , Gonzalez-Carmona Maria A , Mueller Daniel Wilhelm , Eickhoff Regina , de Toni Enrico N. , Waidmann Oliver , Al-Batran Salah-Eddin 
Published: June 2021

TPS4159 Background: The investigator-initiated IMMULAB study investigates the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA), microwave ablation (MWA) or brachytherapy, or - as recommended for tumor larger than 3 cm – by combination with TACE. Patients with extrahepatic disease are excluded. Local ablation is known to induce tumor destruction with subsequent antigen release resulting in host adaptive immune responses. However, tumors could quickly overcome the immune responses by upregulating PD-L1/PD-1 expression and inhibiting the function of CD8+ and CD4+ T cells. Thus, combination of local ablation with an anti-PD1 antibody might display interesting effects by activating immune cells and disabling immune inhibitory mechanisms at the same time. Methods: This is a prospective investigator initiated single-arm multicenter phase II trial investigating immunotherapy with the PD-1 inhibitor pembrolizumab in combination with local ablation in early stage hepatocellular carcinoma (HCC). Patients with a child-pugh classification score ≤ 6, including high risk candidates for local ablation (defined as patients having ≤ 5 tumor nodules with diameters ≤ 7cm [longest axis] each OR patients with vascular infiltration) receive 200mg pembrolizumab i.v. q3w for 2 cycles. Thereafter, radiologic imaging is followed by local ablation on day 1 of cycle 3. Further pembrolizumab (200mg) is applied 2 days after ablation and thereafter every 3 weeks (q3w) for a total treatment duration of up to 12 months. It is planned to enroll 30 pts. Primary efficacy endpoint is the overall response rate (RECIST 1.1) after 2 cycles of pembrolizumab and before performing local ablation aiming in the conversion / downstaging of borderline candidates by pre-interventional treatment with pembrolizumab. Overall recruitment has started; currently (Feb 2021) 18 of 30 planned patients have been enrolled. Clinical trial information: NCT03753659.
Total neoadjuvant FOLFIRINOX or gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2): A nationwide multicenter randomized controlled trial.
Authors: Janssen Quisette , van Dam Jacob L. , Besselink Marc G.H. , Homs Marjolein Y.V. , van Tienhoven Geertjan , Wilmink Johanna W. , Groot Koerkamp Bas ,   Dutch Pancreatic Cancer Group
Published: June 2021

TPS4171 Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.
A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies.
Authors: Niglio Scot Anthony , Girardi Daniel da Motta , Cordes Lisa M. , Ley Lisa , Mallek Marissa , Sierra Ortiz Olena , Cadena Jacqueline , Diaz Carlos , Chalfin Heather , Kydd Andre , Costello Rene , Marciscano Ariel E. , Jones Jennifer C , Salerno Kilian Elizabeth , Valera Vladimir , Figg William Douglas , Dahut William L. , Gulley James L. , Schlom Jeffrey , Apolo Andrea B. 
Published: June 2021

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.
A phase 2, two-stage study of avelumab and axitinib in patients with mismatch repair proficient (MMR-P) recurrent or persistent endometrial cancer (EC).
Authors: Lee Elizabeth Katherine , Xiong Niya , Tayob Nabihah , Krasner Carolyn N. , Buss Mary K. , Campos Susana M. , Wright Alexi A. , Liu Joyce F. , Shea Meghan , Yeku Oladapo O. , Castro Cesar Martin , Porter Rebecca L , Stover Elizabeth , Bouberhan Sara , Moroney John William , Cannistra Stephen A. , Penson Richard T. , Fleming Gini F. , Matulonis Ursula A. , Konstantinopoulos Panagiotis A. 
Published: June 2021

TPS5609 Background: Despite significant strides in understanding the molecular pathogenesis of EC, there remain few effective therapies for recurrent disease. Deeper insight into the roles of disordered tumor vasculature and HIF1α- and VEGF-mediated immunosuppressive effects on myeloid-derived suppressor cells, T-cells, and PD-L1 expression contributed to the development of new targeted regimens. Activity of pembrolizumab and lenvatinib was demonstrated in a phase 2 trial in MMR-P EC (NCT02501096). By inhibiting VEGF receptor (VEGFR) and PD-L1 signaling, immunologically “cold” tumors may become inflamed. However, there are concerns regarding the toxicity of pembrolizumab/lenvatinib and alternatives are sought. The combination of the anti-PD-L1 antibody avelumab with axitinib, an inhibitor of VEGFR 1-3 and PDGFR with more potent IC50 inhibitory activity than lenvatinib, has also shown synergistic activity and is FDA approved as first line treatment for patients with renal cell cancer. We therefore hypothesized that this combination would be well tolerated and efficacious in recurrent MMR-P EC. Methods: This is an investigator-initiated, phase 2, two-stage single cohort trial evaluating avelumab with axitinib in recurrent or persistent EC. Participants must have MMR-P EC of any histology and have received at least one chemotherapeutic regimen, with no upper limit on the number of prior lines received. Prior use of immune checkpoint (IC) inhibitors is excluded. Treatment consists of avelumab 800mg IV every 2 weeks and axitinib 5mg orally twice daily. Co-primary endpoints are progression-free survival at 6 months (PFS6) and objective response rate by RECIST 1.1. Translational objectives include characterization of tumor-infiltrating lymphocytes, infiltrating myeloid cells, expression of IC markers, and whole exome sequencing to evaluate mutations in genes related to DNA repair and immunologic response. This is a two-stage design in the method of Sill et al, with 16 participants anticipated in stage 1 and 19 participants in stage 2, for a total of 35 participants. Accrual is ongoing. Clinical trial information: NCT02912572.
Subcutaneous daratumumab (DARA SC) plus lenalidomide versus lenalidomide alone as maintenance therapy in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are minimal residual disease (MRD) positive after frontline autologous stem cell transplant (ASCT): The phase 3 AURIGA study.
Authors: Shah Nina , Patel Sharmila , Pei Huiling , Qi Ming , Krevvata Maria , Lin Thomas S. , Khare Vipin 
Published: June 2021

TPS8054 Background: DARA, a human anti-CD38 IgGκ monoclonal antibody, is approved in many countries as monotherapy in relapsed/refractory MM (RRMM) and in combination with standard of care (SoC) in RRMM and NDMM. However, no clinical studies have yet compared DARA maintenance versus SoC maintenance. The ongoing phase 3 AURIGA study will evaluate the addition of DARA to lenalidomide maintenance among pts with NDMM who are MRD positive after SoC induction and ASCT. The primary endpoint is the conversion rate to MRD negativity after 1 year of maintenance therapy. Methods: This open-label, multicenter, randomized phase 3 study will enroll approximately 214 pts in the United States aged 18-79 years with NDMM who receive ≥4 cycles of induction followed by ASCT. Pts must enroll within 6 months of ASCT, be naïve for anti-CD38 treatment, have a very good partial response or better per IMWG criteria, and be MRD positive at a threshold of 10–5 by next generation sequencing (NGS) within 30 days of screening. Pts will be stratified by cytogenetic risk (high vs standard/unknown) and randomized 1:1 to 28-day cycles of lenalidomide maintenance (10 mg PO; D1-28 [dose increasing to 15 mg if tolerated]) ± DARA SC (DARA 1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc., San Diego, CA, USA; QW Cycle 1-2, Q2W Cycles 3-6, Q4W C7+). Treatment will continue for up to 36 cycles or until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint is MRD conversion rate after 12 months of maintenance treatment, defined as the proportion of pts who achieve MRD negativity (10–5) by NGS. Additional MRD assessments occur after 18, 24, and 36 months of maintenance. While MRD negativity is associated with improved long-term outcomes for pts with MM and is an emerging, validated prognostic factor, this study is among the first to use MRD negativity as a primary study endpoint. Importantly, MRD negativity allows for earlier efficacy assessment than traditional endpoints such as progression-free survival (PFS) and overall survival (OS). Secondary endpoints include overall MRD conversion rate at any time, sustained MRD negativity lasting ≥12 months, PFS, OS, response rates, duration of complete response, changes in health-related quality of life, and safety. Due to the COVID-19 pandemic, this study has been amended to improve enrollment access by allowing up to 12 months from start of induction therapy to ASCT to mitigate against ASCT delays and to allow greater flexibility for screening and laboratory assessments. Clinical trial information: NCT03901963.