bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 3 PANOVA-3 study: Tumor treating fields (TTFields) therapy concomitant with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic cancer.
Authors: Babiker Hani M. , Macarulla Teresa , Philip Philip Agop , Becerra Carlos Roberto , Dragovich Tomislav , Picozzi Vincent J. 
Published: June 2023

TPS4199 Background: Tumor Treating Fields (TTFields) therapy is a locoregional antimitotic treatment approved for newly diagnosed and recurrent glioblastoma GBM and pleural mesothelioma. TTFields (150 kHz) therapy, with/without chemotherapy, had antiproliferative and anticlonogenic activity in pancreatic cancer cell lines, and reduced tumor volume and weight more than chemotherapy alone in in vivo models. TTFields therapy with gemcitabine and nab-paclitaxel (GnP) was well-tolerated, with promising efficacy in metastatic and locally advanced pancreatic adenocarcinoma (LAPC) in the phase 2 PANOVA study (NCT01971281). LAPC prognosis remains poor despite available therapies, which can negatively impact quality of life (QoL). As such, there remains a need for effective and tolerable treatments. Methods: PANOVA-3 (EF-27, NCT03377491) is a prospective, randomized, phase 3 study investigating the efficacy and safety of TTFields therapy with GnP in patients with LAPC, with a planned enrollment of 556 patients. Key inclusion criteria are: a diagnosis of unresectable LAPC (per NCCN guidelines), ECOG PS of 0–2, and no prior treatment. Patients will be stratified by performance status and geographical region and assigned 1:1 to treatment groups to receive TTFields therapy + GnP or GnP alone. GnP will be administered at a standard dose per standard of care. TTFields therapy (150 kHz, 18h/day) will be delivered by the NovoTTF-200T System until local disease progression per RECIST v1.1. Usage will be tracked by the device. Follow-up will be performed every 4 weeks and computed tomography scans of the chest and abdomen will be taken every 8 weeks until disease progression. Patients will be followed every month until death. The primary endpoint is overall survival and key secondary endpoints include QoL, pain-free survival, and puncture-free survival, which will be compared between treatment groups. Other secondary endpoints include progression-free survival (PFS), local PFS, objective response rate, 1-year survival rate, rate of resectability, and safety. Guidance around usage, lifestyle integration and prevention and management of skin adverse events will be provided by Device Support Specialists and field personnel. Usage information will be provided to patients and physicians to facilitate discussions to optimize outcomes by maximizing time on therapy. Together, these novel support approaches aim to optimize patient usage and outcomes. The trial is currently recruiting at 149 sites, globally. The DMC last reviewed the trial in August 2022, and suggested that the trial continue as planned. Clinical trial information: NCT03377491 .
ARC-20: A phase 1 dose-escalation and dose-expansion study to investigate the safety, tolerability, and pharmacology of HIF-2α inhibitor AB521 monotherapy in patients with clear cell renal cell carcinoma and other solid tumors.
Authors: Choueiri Toni K. , Garmezy Benjamin , Paterson Elaine , Ghasemi Mohammad , Cheng Tzuling , Foster Paul G. , Hauke Ralph J. , Patnaik Amita 
Published: June 2023

TPS4602 Background: Renal cell carcinoma (RCC) is one of the 10 most common neoplasms in the United States. Patients with clear cell RCC (ccRCC) commonly have inactivation of the von Hippel-Lindau tumor suppressor protein, resulting in accumulation of hypoxia-inducible factor alpha (HIFα) subunits (especially HIF-2α) and leading to tumor growth. AB521, an orally bioavailable small molecule inhibitor of HIF-2α, potently inhibits transcription of HIF-2α-dependent genes in cell lines and preclinical species. Single doses of AB521 (3 mg, 10 mg, 30 mg, and 100 mg) and multiple ascending doses of AB521 (15 mg, 30 mg, and 50 mg) have been previously studied in healthy volunteers. ARC-20 is a first-in-patient study to investigate the safety, tolerability, and pharmacology of AB521 monotherapy in patients with solid tumors and evaluate the clinical activity of AB521 in previously treated patients with ccRCC. Methods: ARC-20 (NCT05536141) is a phase 1, multicenter, open-label study. Eligible patients are adults with solid tumors with ≥1 measurable lesion(s) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and an Eastern Cooperative Oncology Group performance status of 0 or 1. ARC-20 has 2 stages, dose escalation and dose expansion. The dose escalation stage uses a standard 3+3 design and includes patients with pathologically confirmed solid tumors and no other available treatment options. Patients will be sequentially assigned to 1 of 4 cohorts evaluating doses of AB521 ranging from 20 to 200 mg/day. Intermediate dose cohorts may be evaluated based on emergent safety or pharmacologic data. The dose expansion stage will evaluate approximately 30 patients with histologically confirmed ccRCC who have received previous treatment for metastasis with an anti-programmed cell death protein 1 (anti-PD-1) therapy and a vascular endothelial growth factor (VEGF)-targeting tyrosine kinase inhibitor (TKI). Patients previously treated with a HIF-2α-targeting therapy are not eligible for dose expansion. Results from the dose-escalation stage will inform the dose and schedule used during dose expansion. Primary endpoints are the incidence of dose-limiting toxicity and adverse events. Secondary endpoints include objective response rate, AB521 plasma concentration, and AB521 pharmacokinetics. Exploratory endpoints include changes in expression of erythropoietin and other HIF-2α driven biomarkers in blood and tumor tissues, along with progression-free survival for ccRCC patients during dose expansion. Clinical trial information: NCT05536141 .
LITESPARK-024: Randomized phase 1/2 study of belzutifan with or without palbociclib for treatment of advanced renal cell carcinoma (RCC).
Authors: McDermott David F. , Peer Avivit , Agarwal Neeraj , Atkins Michael B. , Cornell Jerry , Perini Rodolfo F. , Grossmann Kenneth F. , Gurney Howard 
Published: June 2023

TPS4603 Background: Immunotherapy is a standard-of-care first-line treatment for advanced clear cell RCC (ccRCC). However, many patients (pts) will develop resistance to first-line therapy, and effective second- and later-line treatment options are therefore needed. The von Hippel-Lindau ( VHL) gene is inactivated in approximately 90% of ccRCC cases and results in the constitutive activation of hypoxia-inducible factor 2α (HIF-2α), a key oncogenic driver in RCC. Belzutifan, a first-in-class HIF-2α inhibitor, has demonstrated antitumor activity with manageable safety in previously treated pts with advanced ccRCC. The cyclin-dependent kinase (CDK) pathway is also associated with poor clinical outcomes in ccRCC. In RCC cell lines, the CDK 4/6 inhibitor palbociclib inhibited cell growth. CDK 4/6 inhibition has shown synergistic antiproliferative effects with HIF-2α inhibition in HIF-2α–dependent VHL -/- RCC cell lines. Palbociclib could therefore potentially enhance the efficacy of belzutifan as combination therapy for previously treated pts with advanced RCC. Methods: LITESPARK-024 is a 2-part, open-label, multicenter, phase 1/2 randomized study (NCT05468697). Part 1 is intended to establish the recommended phase 2 dose (RP2D) of belzutifan + palbociclib using a modified toxicity probability interval design. After the RP2D is established, part 2 will directly compare the safety and efficacy of belzutifan monotherapy with belzutifan + palbociclib in pts with advanced ccRCC. In both parts, pts with measurable disease per RECIST v1.1, a KPS score of ≥70%, and histologically confirmed unresectable stage IV RCC with a clear cell component with disease progressing on or after receiving at least 2 systemic treatments (both an anti–PD-1/L1 monoclonal antibody and a VEGF receptor–targeted tyrosine kinase inhibitor, in sequence or in combination) will be enrolled. Up to 30 pts will be enrolled into 3 dose groups in part 1 and will receive belzutifan 120 mg once daily + palbociclib (75, 100, or 125 mg) daily for 21 consecutive days followed by 7 days off. In part 2, approximately 150 pts will be randomly assigned 2:1 to receive belzutifan 120 mg once daily + palbociclib RP2D (21 consecutive days/7 days off) or belzutifan 120 mg once daily. Pts will be stratified by IMDC risk (0 vs 1-2 vs 3-6) and sarcomatoid histology (yes vs no) at randomization in part 2. The primary end point for part 1 is to assess dose-limiting toxicities and adverse events and to determine the RP2D of belzutifan + palbociclib. The primary end point for part 2 is ORR per RECIST v1.1 by investigator assessment. Secondary end points for part 2 are CBR, DOR, and PFS per RECIST v1.1 by investigator assessment, OS, and safety and tolerability. Enrollment began in July 2022. Clinical trial information: NCT05468697 .
MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy in patients (pts) with metastatic urothelial cancer (mUC; Alliance A032001).
Authors: Gupta Shilpa , Ballman Karla V. , Galsky Matt D. , Morris Michael J. , Sridhar Srikala S. , Chen Ronald C. , Chan Timothy An-thy , Wen Yujia , Grivas Petros , Tan Alan , Baghaie Shiva , Rosenberg Jonathan E. 
Published: June 2023

TPS4609 Background: First-line platinum-based chemotherapy followed by maintenance avelumab (Av) is the current preferred standard of care in patients (pts) with mUC who do not progress after platinum-based chemotherapy. There is an unmet need to further improve outcomes by combining Av with an effective, non-cross resistant therapy with non-overlapping toxicity. CABO is an oral inhibitor of MET, VEGFR and TAM family receptors involved in tumor growth, angiogenesis and immune cell regulation and has shown efficacy in UC in combination with PD-1/PD-1L1 inhibitors. We hypothesize that CABO-Av combination will be synergistic in pts with mUC with an acceptable safety profile and will improve upon the benefit seen with Av maintenance in mUC. Methods: MAIN-CAV is a phase III randomized, multicenter, international trial for locally advanced/mUC pts (including N3 only disease) who do not progress after 4-6 cycles of any platinum-based chemotherapy (gem-cis, gem-carbo, MVAC or ddMVAC). 654 adult pts will be randomized 1:1 within 3-10 weeks (wk) after last dose of chemotherapy to receive Av 800 mg IV every 2 wk or combination of Av and CABO 40 mg orally daily for up to 2 yrs. Key eligibility criteria include ECOG PS 0-1, no prior use of immunotherapy (exception of BCG), no central nervous system metastases, no major surgery within 4 wk, no uncontrolled hypertension or cardiovascular disorders. Pts will be stratified based on 1) best response to 1L therapy: complete response vs partial response vs stable disease and 2) presence or absence of visceral metastases. The primary endpoint is overall survival (OS) with assumptions of one-sided alpha of 0.025, power of 80%, median OS of 21 months (mo) on Av arm and hazard ratio (HR) of 0.75, thus hypothesizing a median OS of 28 mo on CABO-Av combination arm. Key secondary endpoints include progression-free survival, safety, tolerability, and activity of CABO-Av compared to Av alone based on RECIST 1.1 and iRECIST criteria and PD-L1 status of pts’ tumors. Quality of life (QOL) will be assessed using EQ-5D-5L, PROMIS-Fatigue 4a, EORTC QLQ-C30, EORTC QLQ-BLM30 between pts on CABO-avelumab vs avelumab alone. Biomarkers of response and resistance to Av will be assessed using baseline archival tissues, baseline and serial blood, ctDNA, stool and urine. Imaging studies will test correlation of established and new radiomic signatures with OS, adverse events and QOL and incorporate both radiologic and biologic features to predict outcomes. This trial would be the first to systematically address whether adding a multitargeted TKI, CABO to Av leads to improved clinical outcomes compared to Av alone. Clinical trial information: NCT05092958 .
ALTER-UC-007: A prospective phase 2 study of anlotinib with gemcitabine and cisplatin or anlotinib with penpulimab as perioperative treatment for patients with muscle-invasive urothelial carcinoma (MIUC).
Authors: Zhang Hailiang , Zhu Yiping , Ye Ding-Wei 
Published: June 2023

TPS4612 Background: Radical surgery involving cystectomy and nephroureterectomy is the standard of care for patients with localized muscle-invasive urothelial carcinoma (MIUC). In recent years, neoadjuvant- and adjuvant-containing multimodality therapies have gradually been adopted in attempt to eradicate micrometastatic disease and improve the outcomes achieved with radical surgery alone. This study aims to evaluate the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor of angiogenesis) with gemcitabine and cisplatin or anlotinib with penpulimab (a humanized anti-PD-1 IgG1 monoclonal antibody) as neoadjuvant and adjuvant therapy in patients with MIUC. Methods: In this open-label, prospective, phase 2 study, eligible patients include those with histologically confirmed clinical stage T1-T4N1-3M0, T3-4N0M0 MIUC (tumors of the bladder, renal pelvis, ureter and urethra) fit and planned for radical cystectomy, nephroureterectomy or ureterectomy. Main exclusion criteria are distant metastatic disease; prior chemotherapy, anti-angiogenic therapy, radiation therapy or immunotherapies; active autoimmune disease; uncontrolled hypertension or patients at high bleeding risk. Patients will be enrolled and receive treatment based on PD-L1 status in tumor tissue. The PD-L1 status of eligible patients will be centralized and assessed using an anti-PD-L1 antibody and an immunohistochemical (IHC) assay. PD-L1 positivity was defined as combined positive score (CPS) ≥1 (previously reported as and equivalent to CPS ≥1%). The study treatment is stratified into two cohorts based on PD-L1 expression levels. In cohort 1, the PD-L1 negative patients with MIUC will receive neoadjuvant anlotinib (12 mg orally QD D1-14 every 3 weeks) + gemcitabine (1000 mg/m2, intravenously [IV] on days 1 and 8) + cisplatin (35 mg/m2 IV on days 1 and 8) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. In cohort 2, PD-L1 positive patients will receive anlotinib (12 mg orally QD D1-14 every 3 weeks) + penpulimab (200 mg IV every 3 weeks) for a maximum of 4 cycles followed by radical surgery and 2 cycles of adjuvant treatment post-surgery. After the completion or discontinuation of the study treatment, safety follow-up and survival follow-up will be performed. Tumor imaging was performed by computed tomography (preferred) or magnetic resonance imaging at baseline, and every 6 weeks during treatment, then every 6 months through year 2. Objective response rate (ORR) is the primary endpoint. Secondary endpoints included pathological complete response rate (pCR), disease-free survival (DFS), overall survival (OS) and safety. Recruitment have begun in October 2022. Currently, the study is active with 1 participant has been enrolled. Clinical trial information: ChiCTR2200063085 .
Adding mitomycin (MM) to bacillus Calmette-Guérin (BCG) as adjuvant intravesical therapy for high-risk, non–muscle-invasive urothelial bladder cancer (NMIBC): BCGMM; ANZUP 1301.
Authors: Hayne Dickon , Stockler Martin R. , Martin Andrew James , McCombie Steve P , Zebic Danka Sinikovic , Bastick Patricia A. , Beardsley Emma Kate , Frydenberg Mark , Green William , Grummet Jeremy , Hawks Cynthia , Ischia Joseph , Mitterdorfer Andrew , Patel Manish , Roberts Matthew , Sengupta Shomik , Srivastav Ratnesh Kumar , Redfern Andrew David , Davis Ian D. ,   The Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: June 2023

TPS4617 Background: Adjuvant intravesical BCG decreases disease recurrence and progression in high-risk, NMIBC, however recurrence occurs in 30% of those affected, despite optimal therapy. Meta-analyses evaluating addition of intravesical MM to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Phase 3 randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will determine the effects of adding MM to the standard BCG after resection of high-risk NMBIC. This is the largest study evaluating this approach in high-risk NMIBC, is of particular relevance given the current BCG shortage, and has the potential to change global practice. Methods: This open-label phase 3 trial is randomizing 500 participants stratified by stage, site of disease, and presence of carcinoma in-situ, in a 1:1 ratio to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG weeks 1, 2, 4, 5, 7, 8; months 4, 5, 7, 8 + MM weeks 3, 6, 9; months 3, 6, 9, see figure below). This provides 85% power to detect an absolute improvement of 10% in 2-year disease free survival (DFS) at 2p = 0.05. Stage 1 (n = 130) was to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, established feasibility. Stage 2, including an additional 370 participants, will provide information on DFS, time to recurrence and progression, overall survival, and identification of potential predictive biomarkers, is estimated to complete accrual by Q2 2023. Progress As of Jan 2023, 484 of 500 planned participants have been recruited from 16 Australian and 1 UK site. In stage 1, successful treatment completion, defined as 75% or more of planned treatment doses, was achieved by 76% in the experimental group (BCGMM) versus 60% in the control group (BCG alone). Clinical trial information: NCT02948543 .
CLIMATE: Assessing the clinical utility of miR-371a-3p as a marker of residual disease in stage 1 testicular germ cell tumour (TGCT) following orchiectomy: ANZUP 1906.
Authors: Conduit Ciara , Grimison Peter S. , Lewin Jeremy Howard , Hansen Aaron Richard , Lynam James F. , Weickhardt Andrew James , Parente Phillip , Campbell David Colin , Hong Wei , Marx Gavin M. , Heron Orlaith Mary , Kuchel Anna , McJannett Margaret Mary , Cusick Thomas , Fontela Antoinette , O Haire Sophie , Zlatic Kristina , Davis Ian D. , Tran Ben ,   The Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group
Published: June 2023

TPS5100 Background: There is impetus to identify biomarkers in TGCT to help select those at high-risk of relapse following orchiectomy and target interventions to prevent over-treatment. miR-371 has been shown to reliably predict presence of active malignancy with higher accuracy than currently available biomarkers. More clinical evidence is required to ascertain its clinical utility as a marker of microscopic disease to guide treatment recommendations in stage 1 TGCT and other settings. Methods: CLIMATE ANZUP1906 (ACTRN12622000247774) is a prospective, single-arm, non-interventional cohort study recruiting adults with clinical stage 1 TGCT entering active surveillance. Eligible participants are recruited within six weeks of orchiectomy and are willing to undergo active surveillance in accordance with the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Surveillance Recommendations (or similar), without adjuvant treatment. Participants with metastases, non-testicular primaries, or history of contralateral TGCT are ineligible. Serum, plasma, and buffy coat samples are collected at consent and every three months until 24 months (and at relapse, if applicable). miR-371 will be assessed using established protocols. Clinical data, including treatment(s), surveillance, and relapses are captured in Australia’s national TGCT registry, iTestis. Archival tissue from diagnosis ± relapse is identified for future translational research. The primary endpoint for CLIMATE is 12-month relapse-free survival of miR-371 positive/negative groups. Key secondary endpoints include miR-371 during surveillance and at relapse, concordance between serum/plasma miR-371 and archival tissue, and health economic analyses. Prior studies suggest ~20% of post-orchidectomy miR-371 samples are positive. A sample size of 200 participants will result in 20 relapses, 160 non-relapses and 20 individuals lost to follow-up, and will permit description of the primary endpoint. Patient-level data from CLIMATE will contribute to a joint analysis of parallel trials evaluating miR-371 in this setting, COG AGCT1531 and SWOG1823. The first participant was recruited to CLIMATE in February 2022. 9/12 study sites in Australia and New Zealand have been activated and 47/200 (24%) have been enrolled. Recruitment is expected to take 36 months, followed by a further 24 months follow-up. Clinical trial information: ACTRN12622000247774 .
P3BEP (ANZUP 1302): An international randomized phase 3 trial of accelerated versus standard BEP chemotherapy for male and female adults and children with intermediate and poor-risk metastatic germ cell tumours (GCTs).
Authors: Zebic Danka Sinikovic , Tran Ben , Martin Andrew James , Pashankar Farzana D. , Mazhar Danish , Huddart Robert A , Wheater Matthew , Walpole Euan Thomas , Dunwoodie Elaine , Feldman Darren R. , Birtle Alison Jane , Wyld David , Lawrence Nicola Jane , Stockler Martin R. , Grimison Peter S. ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: June 2023

TPS5102 Background: Bleomycin, etoposide, and cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for intermediate or poor risk metastatic GCT. Accelerating standard regimens by shortening the cycle length to 2-weekly improved cure rates in other cancers. P3BEP will determine effects of accelerated versus standard BEP in this setting. This is the first international, randomized trial of chemotherapy for intermediate and poor-risk metastatic GCT to include adults and children of both sexes. Methods: This open label, randomized, phase 3 trial is conducted seamlessly in 2-stages. The primary endpoint for stage I (n = 150) was favourable response; and for stage 2 (n = 500) is progression free survival at 2 years (PFS2y). These sample sizes provide > 80% power with a 2-sided type I error rate of 5% to detect an absolute improvement of 21% in the favourable response rate (stage 1) and of 7% in the PFS2y (stage 2). The target population is males and females aged 11 to 45 with intermediate- or poor-risk metastatic GCT of the testis, ovary, retroperitoneum, or mediastinum. Participants are randomized (1:1) to 4 cycles of standard BEP (q3w) or accelerated-BEP (q2w) with cisplatin 20mg/m2 D1-5, etoposide 100mg/m2 D1-5, bleomycin 30 KIU weekly x 12, and pegylated G-CSF D6 or filgrastim daily (Figure 1). Study assessments occur at 30 days after completing chemotherapy, 6 months from randomisation, and after completion of all post-chemotherapy treatments (e.g. surgery). Tumour and blood samples are collected for translational substudies. Progress - As of Jan 2023, 241 participants have been recruited from 22 ANZ sites, 16 UK sites (led by Cambridge Clinical Trials Unit), and 55 USA sites (led by Children’s Oncology Group). The first planned interim analysis for safety (n = 76) identified no safety concerns. The stage I analysis of safety and activity (response rate) for the 1st 150 patients was reviewed by the IDSMC, which recommended continuation of the trial as per protocol. Clinical trial information: NCT02582697 .