bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five- or 10-year colonoscopy for 1-2 non-advanced adenomatous polyps (FORTE) NRG-CC005 study: A randomized phase III non-inferiority trial comparing colorectal cancer incidence in participants with 1-2 non-advanced adenomas randomized to a 5- and 10-year surveillance colonoscopy exam schedule versus a 10-year surveillance colonoscopy exam schedule.
Authors: Schoen Robert E , Bandos Hanna , Corley Douglas , Dueker Jeff , Yothers Greg , Bai Jinbing , Huh Warner King , Bauman Julie E. , Walker Joan L. , Bruner Deborah , Kachnic Lisa A. 
Published: June 2022

TPS3631 Background: Adenomatous polyps are the acknowledged precursors of colorectal cancer (CRC). Identification and removal of adenomas is the mechanism by which screening is effective in reducing CRC incidence and mortality. Patients with 1-2 non-advanced adenomas ( < 1 cm with neither villous components nor high grade dysplasia) are recommended to return at a timing ranging from 5-10 yrs. However, evidence for the benefit, optimal timing, and recommended frequency of surveillance colonoscopy is not available. A randomized, clinical trial to demonstrate the difference in results between 5- or 10-yr surveillance for participants with non-advanced adenoma can guide clinical practice. Methods: NRG-CC005/FORTE is a prospective, randomized, non-blinded, Phase III, non-inferiority clinical trial comparing CRC incidence in participants randomized to recommendation for a 5- and 10-yr vs. a 10-yr only surveillance colonoscopy exam schedule. Other pre-defined exploratory endpoints include incidence of advanced adenomas, CRC mortality, and incidence of stage III-IV CRCs. Stratification factors include age, gender, and time from qualifying colonoscopy to randomization. Participants ≥50 and < 70 yrs of age at the time of randomization with a first-time diagnosis of 1-2 non-advanced tubular adenomas from the qualifying colonoscopy within 4 yrs prior to randomization will be eligible. Participants with a clinical diagnosis of a significant genetic risk for CRC or with a family history of CRC diagnosed at ≤60 yrs in a first degree relative or in two first degree relatives diagnosed at any age are ineligible. Other ineligibility criteria include prior history of CRC or colorectal adenomas, a hyperplastic polyp measuring ≥1 cm or traditional serrated adenomas, or life expectancy < 10 yrs due to comorbid conditions. Collection of blood, stool, and tissue samples is planned. Statistics: The primary endpoint for the trial is CRC incidence. The trial is focused on CRCs diagnosed between year 5 and year 10. By incorporating a window of +/- 1 yr to allow for somewhat earlier and later procedures, as typically occurs in clinical medicine, the primary endpoint will include incident cancers identified in years 4 through 11. A crude 4- to 11-yr incidence rate of 0.387% is assumed for the 5- and 10-yr schedule arm. The study is powered at 90% to detect a non-inferiority margin difference of 0.387% at alpha 5% in CRC incidence rate between two schedules. 9,500 participants are to be enrolled. Support: U10CA180868, -180822, UG1CA189867, U24CA196067 Clinical trial information: NCT05080673.
Myopenia and mechanisms of toxicity in older adults with colorectal cancer (CRC): The M&M study (WF-1806).
Authors: Williams Grant Richard , Bhatia Smita , Klepin Heidi D. , Sanoff Hanna Kelly , Muss Hyman B. , Al-Obaidi Mustafa , Harmon Christian , Richman Joshua , Dressler Emily Van Meter , O'Rourke Mark Allen , Weaver Kathryn E. , Lesser Glenn Jay 
Published: June 2022

TPS3640 Background: CRC is the 2nd most common cause of cancer death in the US, and nearly 60% of CRC cases occur among older adults. There is a critical unmet need to understand the underlying cause(s) of observed variability in chemotherapy toxicity (chemotoxicity) outcomes to minimize adverse outcomes and appropriately personalize therapy for older adults. Low muscle mass, known as myopenia, is prevalent in older adults with CRC (̃60%) and is associated with chemotoxicity and decreased overall survival (OS). However, little is known about trajectories of myopenia and underlying mechanisms of increased toxicities and decreased survival in myopenic patients. We address these gaps in a prospective cohort study, with the central goal of examining the role of myopenia in chemotoxicity in older adults with metastatic CRC undergoing 5-Fluouracil (5FU) based chemotherapy, and to explore the mediating influence of germline genetic variants and pharmacokinetics (PKs) in the association between myopenia and chemotherapy toxicity. Methods: This prospective cohort study is accruing through the Wake Forest NCI Community Oncology Research Program Research Base (WF NCORP) and funded by the NCI grants 2UG1CA189824 and K08CA234225. The study examines the impact of myopenia on chemotoxicity and OS in older adults with newly diagnosed metastatic CRC planning to receive systemic 5FU-based chemotherapy (either as monotherapy or in combination with oxaliplatin and/or irinotecan +/- biologics) (NCT03998202). All patients undergo the Cancer & Aging Resilience Evaluation and Life-Space Evaluation at baseline, 3 and 6 months. Standard of care Computed Tomography (CT) images will be obtained to assess muscle measures (skeletal muscle area/density) at the L3 cross-section. The primary outcome is grades 3 to 5 chemotoxicity measured up to 6 months after initiation of chemotherapy using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. We will assess the association of baseline myopenia and trajectories of myopenia with severe chemotherapy toxicities. Secondary outcome measures include OS at 1 year and chemotoxicities using the Patient Reported Outcomes (PRO) version of the CTCAE. The study also explores the mediating/moderating influence of genetic variation and altered PKs (n = 60) in the association between myopenia and chemotherapy toxicity. To date, the study has accrued 73 of the 300 targeted patients from 110 NCORP practices. Clinical trial information: NCT03998202.
ACCRU-GI-2008: A phase II randomized study of atezolizumab (Atezo) plus a multi-kinase inhibitor (MKI) versus MKI alone in patients with unresectable advanced hepatocellular carcinoma (aHCC) who previously received atezolizumab plus bevacizumab (Bev).
Authors: Ma Wen Wee , Ou Fang-Shu , Li Jenny Jing , Tran Nguyen H. , Babiker Hani M. , Revzin Alexander , Dong Haidong , Nelson Garth D. , Ness Andrew , Schuster Carissa E. , Jia Jingquan , Bekaii-Saab Tanios S. ,   Academic and Community Cancer Research United (ACCRU)
Published: June 2022

TPS4170 Background: IMbrave150 is the first study demonstrating the benefit of anti-PDL1 in the frontline treatment of aHCC, and established Atezo/Bev as a new 1st line standard for aHCC. There is currently limited evidence to guide subsequent therapy for aHCC patients progressing on Atezo/Bev. ACCRU-GI-2008 is designed to determine the benefit of continuing Atezo into 2nd line and the safety of Atezo plus a MKI in patients with aHCC who previously received Atezo/Bev. The study is being conducted across 12 centers in the United States (ClincalTrials.gov#: NCT05168163). Methods: This study utilizes a 2:1 randomized phase II design where eligible patients will receive either Atezo/MKI (experimental arm) or MKI alone (control). Patients will be stratified according to the MKI choice (cabozantinib or lenvatinib, per physician’s decision), etiology of HCC (viral vs. non-viral) and alpha-fetoprotein level ( < 400 vs. > = 400 ng/mL). The major eligibility criteria are histological/cytological diagnosis or clinical diagnosis of HCC per the AASLD or WASL 2018 guidelines, has advanced disease not amendable to curative treatment, previously received and progressed on Atezo/Bev, has received only 1 previous line of systemic therapy (2nd line only), ECOG PS 0-1, Child Pugh Class A, adequate organ reserves and RECIST v1.1 measurable disease; previous MKI for advanced disease is excluded. The primary endpoints are overall survival (OS) and progression free survival (PFS). A total sample size of 122, with 89 PFS events, we will have 80% power to detect an improvement in median PFS from 4 to 7 months, assuming a one-sided significance level of 0.05. With approximately 84 deaths, we will have 80% power to detect an improvement in median OS from 10 to 18 months, assuming a one-sided significance level of 0.05. The overall one-sided significance level, for the study, is 0.1. An OS interim analysis will be conducted at 89 PFS events. Secondary endpoints include objective response, duration of response, and adverse events. Archival tumor and serial blood samples will be collected to evaluate for potential prediction biomarkers and mechanisms of sensitivity/resistance. Baseline and on-treatment tumor biopsy specimens will also be collected from the initial 10 patients of each arm. The study is approved by the ethics committee and enrollment to the study will be underway by Q2/3 2022. Clinical trial information: NCT05168163.
Trial in progress: Durvalumab and olaparib for the treatment of prostate cancer in men predicted to have a high neoantigen load.
Authors: Sokolova Alexandra , Gulati Roman , Cheng Heather H. , Beer Tomasz M. , Graff Julie N , Amador Melanie , Toulouse Andrea , Taylor Kamilah , Bailey Shawna , Smith Steven , Tabatabaei Shaadi , Sinit Ryan , Slottke Rachel , Vuky Jacqueline , Yezefski Todd , Grivas Petros , Yu Evan Y. , Schweizer Michael Thomas 
Published: June 2022

TPS5099 Background: Approximately 30% of patients (pts) treated with definitive surgical and/or radiation therapy for localized prostate adenocarcinoma develop biochemical recurrence (BCR). The optimal time to initiate androgen deprivation therapy (ADT) for such patients is controversial and depends on patient and provider preference, absolute PSA value, and PSA doubling time (PSADT), which has been associated with time to metastasis. Because the time from BCR to metastasis can be long in many cases, strategies allowing pts to avoid ADT while extending metastasis-free survival are desirable. Prior studies have shown that a high tumor neoantigen load correlates with response to anti-PD(L)1. We hypothesized that PARP inhibitor-induced genomic instability may sensitize tumors to anti-PD(L)1 through: i) increasing mutational burden and subsequent tumor neoantigen formation, and/or ii) through activation of other immunogenic pathways (e.g. the STING pathway). This trial investigates an ADT-sparing approach for men predicted to have high neoantigen load and who have BCR prostate cancer. Methods: This is a phase 2 clinical trial testing durvalumab (1500 mg IV every 4 weeks) and olaparib (300 mg PO twice a day) (one cycle = 4 weeks) in men with BCR (PSADT≤10 months) whose tumors are predicted to have high neoantigen load based on: biallelic CDK12 mutations (Cohort A), mismatch repair deficiency (MMRd)/high microsatellite instability (MSI-H) (Cohort B), or loss of function mutations in homologous recombination repair (HRR) genes (Cohort C). Cohorts A and B will receive 3 cycles of durvalumab followed by 3 cycles of the combination of durvalumab and olaparib. Given the proven efficacy of olaparib in prostate cancer patient whose tumors posses an HRR gene mutation, Cohort C will receive 6 full cycles of the combination. Ten patients will be enrolled in each cohort (total n = 30) at two collaborating sites. This study was designed to provide preliminary efficacy data across eligible cohorts, with a primary objective of estimating the proportion of pts with an undetectable PSA at 12 months within each cohort. Secondary objectives include safety, proportion of patients with ≥50% decline in PSA from baseline and quality of life measures. Correlative studies will assess blood and tissue molecular biomarkers for association with outcomes. The study is open with two patients enrolled at the time of abstract submission. Clinical trial information: NCT04336943.
DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801)—A randomized phase 3, double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.
Authors: Niazi Tamim , McBride Sean Matthew , Williams Scott , Davis Ian D. , Stockler Martin R. , Martin Andrew James , Bracken Karen , Roncolato Felicia , Horvath Lisa , Sengupta Shomik , Martin Jarad , Lim Tee , Hughes Simon , McDermott Raymond S. , Catto James W.F. , Kelly Paul J. , Parulekar Wendy R. , Morgan Scott Carlyle , Rendon Ricardo A. , Sweeney Christopher ,   Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
Published: June 2022

TPS5103 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analog (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile, and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or salvage therapy for very high-risk PC. Methods: This study is a randomized (1:1), phase 3, placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC on conventional imaging; or very high-risk features with PSA persistence or rise within one year following RP. The trial is stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomization. Participants are allowed nonsteroidal antiandrogen in addition to LHRHA for up to 90 days prior to randomization. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety, and resistance to study treatment. Clinical trial information: NCT04136353.
Phase 1 study of JNJ-69086420, an actinium-225-labeled antibody targeting human kallikrein-2, for advanced prostate cancer.
Authors: Morris Michael J. , Sartor A. Oliver , Wong Jeffrey Y.C. , Max Steven I , Xie Hong , Yu Alex , Divgi Chaitanya R. , Patricia Daniel , Avadhani Anjali Narayan , Pandit-Taskar Neeta , Barata Pedro C. , Nordquist Luke T. 
Published: June 2022

TPS5104 Background: Radioligand therapy for metastatic castration resistant prostate cancer (mCRPC) has been shown to prolong survival, delay disease progression, and improve quality of life, raising hopes that these gains will be amplified with even more cancer-specific targets and more powerful radioligands. Human kallikrein-related peptidase 2 (hK2) is a tumor-associated member of the kallikrein family that shares significant homology to prostate-specific antigen and is minimally expressed in normal non-prostate tissues. JNJ-69086420 (JNJ-420; 225Ac-DOTA-h11B6 [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]), is a first-in-class radioimmunotherapy targeted to hK2 antigen. In a phase 0 study of [111In]-DOTA-h11B6, patients with mCRPC (progressed on standard therapies), treatment with a single dose of [111In]-DOTA-h11B6 (2 mg) with/without 8 mg h11B6, demonstrated safety, good tumor localization, nominal normal-organ uptake, and no difference in pharmacokinetics (PK) between 2 and 10 mg antibody mass (Morris et al. J Clin Oncol. 2021 39:6 suppl, 122). We have initiated the first-in-human study to assess the safety, PK, pharmacodynamic (PD), and clinical activity of Ac-225 radiolabeled JNJ-420, to determine its recommended phase 2 dose (RP2D) in adults with advanced PC. Methods: This open-label, multicenter, phase 1 study will recruit approximately 50 men (aged ≥18 years) with advanced PC across dose escalation (Part 1) and expansion (Part 2) parts. Key eligibility criteria: mCRPC with histologic confirmation of adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate organ function based on hematology and serum chemistry, and 1 or more prior novel androgen receptor-targeted therapies (prior chemotherapy acceptable). Key exclusion criteria: prior treatment with radium/strontium/samarium/radioconjugate therapy, superscan findings as protocol defined, active central nervous system metastases. In Part 1, men will receive intravenous (IV) injection of 50 μCi/ 2 mg JNJ-420 (once every 8 weeks) with one or multiple doses; escalation of dose levels to be based on dose limiting toxicities (DLTs) evaluation, until RP2D identification. In Part 2, JNJ-420 is to be given at one of the RP2D(s) determined in Part 1. Primary endpoint is safety (incidence and severity [grading per NCI-CTCAE V5.0] of AEs including DLTs). Secondary endpoints include prostate specific antigen response rate, overall response rate (PCWG3 modified RECIST 1.1 criteria), PK, PD, immunogenicity, and biomarker analyses. Enrollment began in Dec 2020; as of 10 Feb 2022, 4 sites have been initiated and 23 patients enrolled; currently, dose escalation is ongoing. Clinical trial information: NCT04644770.
A phase 1/2 study of REGN4336, a PSMAxCD3 bispecific antibody, alone and in combination with cemiplimab in patients with metastatic castration-resistant prostate cancer.
Authors: Kelly William Kevin , Thanigaimani Pradeep , Sun Furong , Seebach Frank A. , Lowy Israel , Sandigursky Sabina , Miller Elizabeth 
Published: June 2022

TPS5105 Background: Prostate cancer is the leading cause of new cancer diagnoses and the second most common cause of cancer-related death in American men. Prognosis is especially poor for men with metastatic castration resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA) is highly expressed on malignant prostate tissue but shows limited expression on normal tissue. As such, PSMA is an excellent research target for treatment of mCRPC. REGN4336 is a PSMAxCD3 bispecific antibody designed to facilitate T-cell–mediated killing of PSMA-expressing tumor cells. In preclinical models, REGN4336 demonstrated strong PSMA-dependent antitumor activity that was dose-dependent. Preclinical data also support clinical research into the combination of REGN4336 with cemiplimab (anti–programmed cell death-1) for treating mCRPC. Methods: This is an open-label, Phase 1/2, first-in-human, multicenter dose-escalation study with dose expansion evaluating safety, tolerability, pharmacokinetics (PK), and antitumor activity of REGN4336 administered subcutaneously alone and in combination with intravenous cemiplimab in patients with mCRPC (NCT05125016). Patients must have received at least two prior lines of systemic therapy approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. In this study, REGN4336 as monotherapy is administered weekly but may be extended to once every 3 weeks following identification of the minimal pharmacologically active dose. REGN4336 in combination with cemiplimab (350 mg) will be administered once every 3 weeks after a 4-week REGN4336 monotherapy lead-in cycle. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate the safety, tolerability, PK, and recommended phase 2 dosing regimen (RP2DR) of REGN4336 alone and in-combination with cemiplimab. Expansion cohort(s) will be enrolled once RP2DRs have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate with REGN4336 alone or in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, PSMA positron emission tomography/computed tomography scans will be performed at predefined timepoints on study. This study is currently open to enrollment. Clinical trial information: NCT03088540.
A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial.
Authors: Lee Jung-Yun , Park Junsik , Lee Jae Kwan , Jeong Dae Hoon , Kim Se Ik , Choi Min Chul , Kim Byoung-Gie , Lim Myong Cheol , Park Jeong-Yeol 
Published: June 2022

TPS5610 Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods: The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate and 4 of planned 44 patients have been enrolled. Clinical trial information: NCT04734665.