bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial testing to assess cognitive function in patients with cancer being treated with immunotherapy.
Authors: Shahani Shobha , Ajrouch Ali , Hanna Nasser H. 
Published: July 2024

TPS1644 Background: The advent of immunotherapy (IT) has revolutionized lung cancer treatment, becoming a primary modality from Stages Ib to IV. While the short-term side effects of IT are well documented, its long-term impact on cognitive function are under explored. This is a crucial area of investigation given the significant impact of cognitive health on the quality of life in cancer survivors. Preclinical investigations suggest neurocognitive alterations in IT-treated patients, evidenced by increased microglial activation and cytokine release, contributing to observed cognitive deficits such as impaired cued fear memory and object recognition. This study leverages the Montreal Cognitive Assessment (MoCA) to investigate these potential cognitive changes in a clinical setting, aiming to provide crucial insights into the long-term effects of IT. Methods: This single-center, open-label pilot study enrolls patients with various cancer types and stages undergoing IT. Exclusion criteria include prior history of underlying cognitive dysfunction, dementia, depression or psychiatric illness, history of brain metastasis or radiation. The study compromises three cohorts: those receiving IT alone, those undergoing chemo-immunotherapy, and a control group with no active treatment (in remission with prior history of cancer and have received IT in the past). Each of the IT and chemo-immunotherapy groups will include 72 patients, while the control group will consist of 40 participants. Baseline cognitive function is assessed using the MoCA scale, with follow-up assessments at 3 and 6 months from baseline. Patient enrollment commenced in April 2022, with 4 patients enrolled in the IT group, 16 in the chemo-IT group, and 32 in the control group. The primary objective is to assess the Cognitive function change in each individual group of patients. The secondary objective is to assess change of MoCA scores after 3 months and 6 months in patients receiving immunotherapy alone in lung cancer patients. The changes in MoCA scores will be plotted and summarized with mean change, standard deviation of change and standard errors of mean change. MoCA scores at baseline and at 6 months will be compared using paired t-tests. The study will analyze the rate of change in MoCA scores over time, comparing outcomes across the treatment cohorts. Clinical trial information: NCT06160700 .
ESORES-Trial: Surgery as needed versus surgery on principle in patients with postneoadjuvant clinical complete tumor response of esophageal cancer.
Authors: Hipp Julian , Bruns Christiane J. , Schmoor Claudia , Weis Joachim , Hoeppner Jens 
Published: July 2024

TPS4185 Background: A substantial fraction of patients with esophageal cancer (EC) shows post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients. Active surveillance (AS) and surgery as needed may be a treatment alternative for patients with clinical complete response (cCR). Methods: ESORES is a multicenter randomized controlled parallel-group non-inferiority trial. Patients are randomized either to surgery on principle and subsequent follow-up (Arm B) or clinical response evaluation (CRE) and surgery as needed (Arm A). CRE consists of esophagogastroscopy with deep biopsies (EGD), endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) of suspicious lymph nodes, and F18-FDG-PET CT. In case of residual tumor (non-CR) after CRE, treatment is surgery. Patients with cCR will proceed with AS and surgery only if local regrowth occurs. AS comprises EGD, EUS-FNA and CT-Thorax/Abdomen at 3/6/9/12/18/24 months and yearly thereafter. A sample size of 670 patients is needed to demonstrate non-inferiority of Arm A vs. Arm B with regard to overall survival (OS) at a one-sided significance level of 5%, choosing a hazard ratio of 1.325 as non-inferiority margin which corresponds to a difference in 3-year OS rates of 8%. Superiority with regard to quality of life will be evaluated hierarchically only after non-inferiority with respect to OS has been shown. Key inclusion criteria: histologically verified EC, TNM stage ycT0-3 ycN0 ycM0, completion of neoadjuvant chemotherapy (nCT) or chemoradiation (nCRT) (irrespective of specific protocol), no visible lymphatic or distant metastasis in routine postneoadjuvant CT. Key exclusion criteria: postneoadjuvant dysphagia and/or esophageal obstruction, tumors of the cervical esophagus, tumors with direct proximity to the membranous part of the central airways (if regrowth is suspected to evoke locally irresectable ryT4b-stage), TNM stage cT4/ycT4 and/or cM1/ycM1, tumor progression during/after nCT/nCRT, and nCRT with >50 Gy radiation dose. Primary endpoints (hierarchically tested): 1) OS, 2) EORTC QLQ C30 global quality of life subscale. Secondary endpoints: Efficacy: long term tumor control, disease free survival, distant metastasis/local recurrence/regional recurrence; quality of life: EORTC QLQ C30, QLQ OES18, fear of progression: FoP-Q-12, surgery-free survival time in Arm A, patients’ satisfaction: EORTC OUT-PATSAT7; economic impact: days and costs of hospitalization; Safety: Interventional Safety: 3-Year-Comprehensive Complication Index, Oncological Safety (diagnostic accuracy of CRE, resection status (R0/R1/R2), irresectable regrowth during AS). Enrollment of patients started on January 30th, 2024. Clinical trial information: DRKS00032613 .
QUIC: Phase 2 study of gemcitabine, cisplatin, quemliclustat (AB680), and zimberelimab (AB122) during first-line treatment of advanced biliary tract cancers (BTC)—Big Ten Cancer Research Consortium study BTCRC-GI22-564.
Authors: Ebben John , Eickhoff Jens C. , Deming Dustin A. , Hochster Howard S. , Turk Anita Ahmed , Sahai Vaibhav , Uboha Nataliya Volodymyrivna 
Published: July 2024

TPS4195 Background: Despite recent approvals of immune checkpoint inhibitors with chemotherapy in the first-line setting, the median overall survival (mOS) for patients with advanced biliary tract cancer (BTC) remains less than 15 months. CD73 is a key enzyme responsible for the conversion of extracellular adenosine 5’-monophosphate into adenosine and may play an important role in creating an immunosuppressed tumor microenvironment. High expression of CD73 in BTC is associated with decreased OS. Quemliclustat (Q) is a potent, selective, reversible inhibitor of CD73. Q in combination with chemotherapy has demonstrated promising activity in patients with advanced pancreatic cancer without significant increase in adverse events. The BTCRC-GI22-564 study evaluates safety and preliminary efficacy of Q in combination with zimberelimab (Z), a monoclonal antibody targeting human PD-1, with gemcitabine and cisplatin (GC) as first-line therapy for patients with advanced BTC, QUIC (Q and Immunotherapy in Cholangiocarcinoma). Methods: This is an open label, single arm, phase II multi-site trial, evaluating Q and Z in combination with GC in patients with advanced BTC who have not received systemic treatment for advanced disease or who completed adjuvant therapy > 6 months prior to development of recurrent disease. Chemotherapy is given on days 1, 8, 22 and 29 of each 42-day cycle as per local standards. Z is administered at a fixed dose of 360 mg via IV infusion every 3 weeks. Q is administered via IV infusion on days 1, 15, and 29. A safety run-in portion built into the study is planned to enroll 6 subjects to ensure there are no dose limiting toxicities (DLT). If a study defined DLT is observed, Q, gemcitabine and cisplatin will be reduced by 1 dose level, and an additional 6 subjects will be enrolled in the safety run-in portion. The primary efficacy endpoint is median progression free survival (mPFS) with null and alternative survival of 6.0 and 10.0 months, respectively. Based on an accrual rate of 3 patients per month, we expect to accrue 33-39 patients which will provide at least 83% power with a one-sided alpha of 0.1. Secondary endpoints include mOS, disease control rate, overall response rate, and duration of response. Correlative endpoints will assess clinical outcomes with immune infiltration within tumor microenvironment, CD73 and PD-L1 expression. The QUIC study is currently open to enrollment through BTCRC. Clinical trial information: NCT06048133 .
VIRAGE: A phase IIb, open-label, randomized study of nab-paclitaxel and gemcitabine plus/minus VCN-01 in patients with metastatic pancreatic cancer.
Authors: Garcia-Carbonero Rocio , Pazo Cid Roberto , Macarulla Teresa , Nguyen Alana , Kim Edward , Laquente Berta , Seery Tara Elisabeth , Cazorla Mireya , Guillen-Ponce Carmen , De Castro Eva Martinez , Anton-Pascual Beatriz , Muñoz Martín Andrés J. , Lobo Miriam , Garrido-Laguna Ignacio , Le Charles , Kaleko Michael , Shallcross Mary Ann , Blasco Carmen , Cascallo Manel , Hidalgo Manuel 
Published: July 2024

TPS4210 Background: VCN-01 is a modified oncolytic adenovirus type 5 (Ad5) designed to replicate selectively in cancer cells with a dysfunctional RB1-E2F pathway and express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. Results obtained in a previous phase I trial in patients with solid tumors, including metastatic pancreatic cancer, showed that a single systemic administration of VCN-01 is feasible and has an acceptable safety profile alone or when combined with standard of care chemotherapy (SoC) nab-paclitaxel plus gemcitabine (NCT02045602). VCN-01 reached and replicated in tumors and encouraging biological and clinical activity was observed when administered in combination with SoC to patients with metastatic pancreatic adenocarcinoma (mPDAC). Based on the promising phase I results, a phase IIb, open-label, randomized study was initiated to evaluate treatment with two doses of VCN-01 in combination with nab-paclitaxel and gemcitabine in patients with mPDAC. Methods: VIRAGE is a multi-center, open label, randomized, 2-parallel arm, phase IIb trial that evaluates the safety, tolerability and efficacy of two separate VCN-01 intravenous administrations (1x1013 vp/dose) in combination with SoC (nab-paclitaxel at 125mg/m2 and gemcitabine at 1000mg/m2 ) as first line treatment in chemonaïve mPDAC patients. A total of 92 subjects in North America and European Union will be recruited and randomized (1:1) to receive either SoC nab-paclitaxel and gemcitabine (on days 1, 8 and 15 of each 28-day cycle) (Arm I), or doses of VCN-01 administered 1 week prior to SoC nab-paclitaxel and gemcitabine in each of cycle 1 (week 1) and cycle 4 (week 14) (Arm II). Cycles 1 and 4 of Arm II will be 35-day cycles to accommodate VCN-01 dosing, while all other SoC cycles will be 28 days. Patients will continue study treatment until progressive disease (PD), unacceptable toxicity or patient’s/investigator’s decision. The primary endpoint is overall survival (OS) and the assessment of safety and tolerability of two intravenous doses of VCN-01 added to SoC. The secondary objectives include time-to-progression (TTP), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), duration of the response (DoR), 1-year OS and PFS rates, and serial changes in tumor markers (Ca19.9). At 31 Jan 2024, the enrollment is ongoing in US and Spanish sites. Clinical trial information: NCT05673811 .
Phase 2 randomized study of rintatolimod following FOLFIRINOX in patients with locally advanced pancreatic adenocarcinoma.
Authors: Klute Kelsey , Picozzi Vincent J. , Gabrail Nashat , Hollingsworth Michael A. , McAleer Christopher , Young Diane , Strayer David Rodney 
Published: July 2024

TPS4214 Background: The immunosuppressive microenvironment of pancreatic ductal adenocarcinoma (PDAC) is a driver of its lethality and resistance to immunotherapy. Strategies which modulate the immunosuppressive milieu have the potential to improve the anti-tumor response and improve outcomes in patients with PDAC. Rintatolimod is a synthetic double-stranded RNA molecule that activates the toll-like receptor 3 (TLR3) present on dendritic cells, B-cells, natural killer cells and pancreatic epithelial cells. TLR3 stimulation may increase cytotoxic T-cell activity in PDAC through dendritic cell maturation, antigen priming and downstream proliferation of cytotoxic T-cells. Twenty-seven patients were treated with rintatolimod in a single center Named Patient Program at Erasmus University Medical Center in Rotterdam between January 2017 and February 2019. All had locally advanced or metastatic PDAC which had not progressed on FOLFIRINOX (median 8 cycles). Maintenance rintatolimod, administered intravenously twice weekly for up to 18 weeks, was generally well tolerated. The most common toxicities were grade 1-2 myalgia (30%), chills (52%) and fatigue (30%); no toxicities ≥ grade 3 were observed. Progression-free and overall survival (from cycle 1 FOLFIRINOX) were 13 and 19 months. Methods: This is a phase 2 randomized, open-label, multicenter clinical trial. The primary objective is to assess the efficacy of rintatolimod compared to observation in subjects with locally advanced PDAC which has not progressed after FOLFIRINOX. Eligible patients have completed at least 4 months of FOLFIRINOX, have no evidence of progressive disease, have measurable disease by RECIST v1.1, Karnofsky Performance Status ≥80 and have adequate organ function. Subjects with resected PDAC or metastatic disease are not eligible. Subjects are randomized 2:1 to rintatolimod vs. observation. Rintatolimod is administered intravenously twice weekly until disease progression in the experimental arm. Cross-sectional imaging is performed every 8 weeks in both arms. The primary endpoint is progression-free survival, as assessed by the investigator. Secondary endpoints include overall survival, objective response rate, duration of response and safety, as assessed by CTCAE v5.0. Exploratory endpoints include quality of life and changes in immune cell composition and T-cell response in the peripheral blood to characterize the immunomodulatory effects of rintatolimod. The planned sample size is 90 subjects. The final analysis will be performed after 64 events (disease progression or death) have been observed. The study is powered to detect a hazard ratio of 0.47 for median PFS with 80% power and significance level of 5%. Clinical trial information: NCT05494697 .
A phase I/II study of intraperitoneal (IP) paclitaxel (PTX) in patients with metastatic appendiceal adenocarcinoma.
Authors: Shen John Paul Y.C. , Ito Ichiaki , Yousef Abdelrahman M.G. , White Michael , Fournier Keith F. , Helmink Beth A 
Published: July 2024

TPS4215 Background: Appendiceal cancer is a rare, orphan disease, that is unfortunately becoming more common. There is growing data from our lab and others that particular subtypes of AA do not respond to CRC chemotherapy. The use of CRC chemotherapy to treat patients with AA tragically results in many patients enduring side effects from chemotherapy that is ineffective; however, this practice will likely continue unless AA-specific treatments are developed. The Shen lab has recently tested IP paclitaxel (PTX) in orthotopic PDX models of AA. After allowing implanted tumors to grow for four weeks to simulate diffuse peritoneal metastases, baseline MRI was performed and mice were randomly assigned to treatment groups of four mice and intraperitoneally (IP) administered increasing doses of PTX. Marked response was seen in all three models at dose of 25 mg/kg IP weekly, with a near complete response in model AAPDX-10. This dose given IP was well tolerated by the mice, notably this dose exceeds the know lethal IV PTX dose. Methods: The Phase I component of this study will be a prospective single-arm intervention trial giving IP PTX every 2 weeks for a total of 5 doses with primary endpoint of safety and tolerability (MTD determination). Each patient will have an initial diagnostic laparoscopy where PCI score will be calculated and IP catheter placed, dx lap is repeated at the end of study after 5 biweekly doses. For the Phase 1 portion of the trial a Bayesian Optimal Interval (BOIN) approach will be used to determine recommended phase 2 dose (RP2D). All patients treated at that dose or higher will be included in Phase 2 component of the study where the primary objective is response, determined by change in PCI score. With 15 patients Based on historical data, we estimate that the proportion of patients who will demonstrate an objective response without going on trial is 0.05, i.e., the null hypothesis is a 0.05 ORR. Treatment is expected to raise this proportion to 30%. Using an exact binomial test with one-sided type I error of 0.05, we will reject the null if at least 3 patients achieve response. This test has power of 87%. Secondary end points include pathologic, biochemical and radiographic response, PFS, OS, and the influence of KRAS/GNAS/TP53 mutation on response. PK measurements will also be performed during the Phase 1 portion of the trial to determine the degree to which the IP injected PTX enters the blood stream. Patients will be followed for up to 1 year. Adverse events (AEs) will be captured and graded using the National Cancer Institute’s (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v. 5.0 (or latest version) and will include the event term, grading, duration and attribution. Attribution to the study agent or intervention will be determined by the PI, Co-PI or treating physician. Clinical trial information: NCT06207305 . [Table: see text]
Open-label, phase 2 study of adebrelimab combined with fuzuloparib in the treatment of patients with HRD-positive, recurrent platinum-resistant ovarian cancer.
Authors: Chen Jian , Zou JianPing , Yu Haijuan , Liu Li , Zang Lele , Sun Yang 
Published: July 2024

TPS5634 Background: Adebrelimab, a humanized anti-PD-L1 monoclonal antibody, selectively targets PD-L1 molecules to inhibit the PD-1/PD-L1 pathway, reversing tumor-induced immune tolerance and revitalizing the immune system's capacity to combat tumors. Fuzuloparib, a novel PARP inhibitor, impedes the activity of poly (ADP-ribose) polymerase, halting the DNA repair mechanism for single-stranded breaks, resulting in DNA damage accumulation and consequent cancer cell apoptosis. Emerging evidence strongly supports that PARP inhibitors significantly extend progression-free survival in homologous recombination-deficient (HRD)-positive ovarian cancer. The TOPACIO study demonstrated that the combination of niraparib and pembrolizumab for platinum-resistant ovarian cancer achieved an objective response rate (ORR) of 18%, with durable responses in patients. This underscores the potential of integrating PARP inhibitors with immune checkpoint inhibitors in clinical protocols. For platinum-resistant recurrent ovarian cancer, known for its challenging prognosis, we propose conducting exploratory clinical trials on the combination of adebrelimab and fuzuloparib, aiming to establish robust evidence for future clinical applications. Methods: This open-label, single-arm, Phase 2 study aims to evaluate the anti-tumor activity and safety of adebrelimab in combination with fuzuloparib in approximately 37 patients with HRD-positive, recurrent platinum-resistant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (hereinafter referred to as ovarian cancer). The primary endpoint is to determine the objective response rate of the combined treatment regimen, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints encompass disease control rate, progression-free survival overall survival, along with the assessment of safety and tolerability. Patients must be aged 18-70 years with an Eastern Cooperative Oncology Group performance status of 0–1 and have recurrent histologically confirmed ovarian cancer with HRD-positive tumor. Patients must have progressed within less than 6 months after the last treatment with platinum-containing chemotherapy. HRD status confirmed by testing BRCA gene, loss of heterozygosity, telomeric allelic imbalance and large-scale transition. Adebrelimab (20 mg/kg) is administered intravenously every 3 weeks and fuzuloparib (100mg) is administered orally twice daily as until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met. This clinical trial is in progress and 7 patients have been enrolled. Clinical trial information: NCT05753826 .
GOG3069: Phase 2 study of alpelisib and fulvestrant for PIK3CA-mutated estrogen receptor (ER)-positive endometrioid endometrial cancers.
Authors: Gaillard Stephanie , Sill Michael , Klein Jennifer , Reid Thomas , Callahan Michael , Fehniger Julia , Sobecki Janelle , Gold Michael A. , Herzog Thomas J , Slomovitz Brian M. , Matulonis Ursula A. 
Published: July 2024

TPS5639 Background: Treatment options for persistent, metastatic, or recurrent endometrial cancer continues to evolve as we learn more about the molecular landscape of this disease. Recent studies have shown a benefit to endocrine-based combinations such as aromatase inhibitors with mTOR or CDK4/6 inhibitors especially in patients who had not received prior chemotherapy ( 1– 3). The presence of oncogenic PIK3CA mutations have been shown to impact response to aromatase inhibitors in breast cancer. The combination of alpelisib and fulvestrant was approved for the treatment of metastatic hormone receptor-positive, HER2-negative breast cancer harboring oncogenic mutations in the PIK3CA gene that progressed on prior endocrine therapy( 4). PIK3CA mutations are commonly identified in endometrial cancers and may similarly confer endocrine resistance. GOG3069 is a phase II trial designed to evaluate the efficacy and safety of alpelisib and fulvestrant in a biomarker-selected endometrial cancer patient population. Methods: This is a phase II non-randomized, open label, multicenter, two-stage study. Eligible patients must have advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma with measurable disease by RECISTv1.1 criteria. Patients cannot be curable by surgery or radiotherapy. Disease must be of endometrioid histology with positive expression of estrogen receptor (defined as ≥1% of tumor cells demonstrating positive nuclear staining by immunohistochemistry) and oncogenic PIK3CA mutation. Patients may have received no more than 3 prior lines of therapy including 1 prior line of systemic chemotherapy. Enrolled patients will receive treatment with alpelisib 300mg orally daily and fulvestrant 500mg IM on Day 1 and Day 15 of Cycle 1, then 500mg IM on Day 1 of each 28-day cycle. The primary endpoint is overall response rate as measured by RECISTv1.1-defined tumor response. Secondary endpoints include safety, tolerability, progression-free survival, duration of response, and 24-month overall survival rate. GOG3069 activated in November 2023 and expects to enroll across 15 US sites. The statistical plan uses a conditional stratified design factoring differing probabilities of response based on whether the patient had prior chemotherapy exposure. ClinicalTrials.gov Identifier: NCT05154487 References: 1. B. M. Slomovitz et al., Gynecologic Oncology. 164, 481–491 (2022); 2. P. A. Konstantinopoulos et al., J Clin Oncol. 41, 599–608 (2023); 3. G. Colon-Otero et al., ESMO Open. 5, e000926 (2020); 4. F. André et al., N Engl J Med. 380, 1929–1940 (2019). Clinical trial information: NCT05154487 .