bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWOG S1823/CCTG GCC1: Translational observational investigational study of the liquid biomarker microRNA 371a-3p in newly diagnosed germ cell tumours—Real-world trial design, rapid accrual, and robust secondary use of data opportunities.
Authors: Morin Coulombe Antoine , Ozgun Guliz , Johnson Rebecca , Lewis Mark Andrew , Adra Nabil , Eggener Scott E. , Roth Bruce J. , Ryan Christopher W. , Porter Christopher , Millard Fred , Jang Thomas , Hamilton Robert James , Einhorn Lawrence H. , Kollmannsberger Christian K. , Arnold Kathryn B. , Blanke Charles David , Daneshmand Siamak , Nichols Craig R. , Nappi Lucia , Harzstark Andrea 
Published: June 2023

TPS5103 Background: With the discovery of the very promising, germ cell malignancy (GCM) specific, liquid biomarker microRNA 371a-3p (miR371), the investigative trajectory has markedly accelerated. With its outstanding, previously-reported specificity and positive predictive value, miR371 likely will become a powerful tool for clinical decision-making. The primary objective of SWOG S1823/CCTG GCC1 [NCT03067181] is to define the operating characteristics of plasma miR371 expression at the time of clinical relapse for low/moderate risk non-seminoma GCM patients on active surveillance. Methods: S1823 is a prospective, observational, adult GCM translational trial which is actively accruing. Broad eligibility includes all newly diagnosed adult GCM patients. Patients are assigned to low (<25% risk of relapse), moderate (25-90% risk of relapse) or high (≥90% risk of harboring active GCM) risk groups. Pragmatic logistics include using Streck tubes and centralized processing for miR371 sample processing and analytics. Research samples were drawn at the time of routine blood draws minimizing patient burden. Source documents are submitted along with case report forms. This data-gathering model gives an important data quality-control check. S1823 began in July 2020 and has since accelerated its accrual to consistently predicted new enrollments of 20-30 cases/month. As of January 2023, the study enrolled 389 low-risk, 114 moderate-risk and 146 high-risk patients (657 total). Interim analysis is planned at the time 40 non-seminoma GCM patients have relapsed and is anticipated in late 2023 to early 2024. 404 centers have opened S1823. 3 Canadian centers have enrolled >10 patients (range 11-51). 17 USA institutions have enrolled >10 patients (range 11-112). In North America, 9 of the 12-storied GCM clinical research programs have had robust participation. The leading accruing organization was the Kaiser Permanente system where 112 patients have been enrolled. In Canada, all population centers contributed proportionally. In the USA, the dominant enrollment comes from the west coast and mid-west. Proportional enrollments have been seen in Hispanic and Asian populations. The entire study provides rich opportunities for a variety of secondary use and patterns of care projects that will begin to roll out over the next year. Clinical trial information: NCT03067181 . [Table: see text]
A phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer: ARAMON study.
Authors: Gao Xin , Smith Matthew Raymond , Scher Howard I. , Verholen Frank , Adorjan Patrick , Dissanayake Manjari , Laccetti Andrew Leonard 
Published: June 2023

TPS5111 Background: Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration. In the phase 3 ARAMIS study (NCT02200614) of patients with nonmetastatic castration-resistant prostate cancer, treatment with darolutamide significantly improved metastasis-free survival and overall survival versus placebo, with a favorable safety profile. The incidences of central nervous system adverse events (AEs; e.g. falls, memory impairment, and depression) showed a ≤2% difference between the darolutamide and placebo groups. Fatigue was the only AE with an incidence of > 10% for darolutamide (13.2% vs 8.3% for placebo). In a separate neuroimaging study of healthy volunteers, cerebral blood flow was not altered in patients treated with darolutamide but was significantly reduced in brain areas related to cognition in patients treated with enzalutamide. Furthermore, it is postulated that the low blood–brain barrier penetration of darolutamide may result in lower serum testosterone elevations than those seen with enzalutamide, with the potential of leading to fewer associated feminizing AEs. The objective of ARAMON (NCT05526248) is to compare the effect of darolutamide and enzalutamide monotherapy on post-treatment testosterone levels in patients with hormone-naive prostate cancer experiencing biochemical recurrence after definitive treatment for localized disease. Methods: ARAMON is a two-stage, open-label, phase 2 study of patients with histologically or cytologically confirmed adenocarcinoma of the prostate who have biochemical recurrence after radical primary prostatectomy or radiation therapy, with a prostate-specific antigen (PSA) doubling time of ≤20 months, baseline serum testosterone > 150 ng/dL, and Eastern Cooperative Oncology Group performance status 0/1. During a 52-week lead-in phase, 25 patients will receive darolutamide 600 mg twice daily. If criteria based on serum testosterone increase from baseline to Week 12 are met, the study will proceed to a 52-week randomized phase in which the effects of darolutamide (600 mg twice daily, n = 20) will be compared with the effects of enzalutamide (160 mg once daily, n = 20). The primary endpoint of both phases is the change in serum testosterone level from baseline to Week 12. Secondary endpoints of the randomized phase include the change in serum testosterone levels from baseline to Weeks 24 and 52; PSA at Weeks 4, 12, 24, 36, and 52; changes in blood levels of markers for glucose, lipid metabolism, and endocrine function related to sex hormones; safety; and quality of life. Safety will be assessed through AE monitoring. The first of the 25 planned patients in the lead-in phase was enrolled on January 13, 2023. Clinical trial information: NCT05526248 .
Phase 1/2a study of PRL-02, a long-acting intramuscular (IM) depot injection of abiraterone decanoate, in patients (pts) with advanced prostate cancer.
Authors: Shore Neal D. , Avitia Jose W. , Bailen James L. , Nordquist Luke T. , Richardson William , Peer Cody J. , Figg William Douglas , Walling Jacqueline M. , Eisner Joel Robert , Sharp Matthew , Schotzinger Robert J. , Moore William R. , Tutrone Ronald F. 
Published: June 2023

TPS5117 Background: PRL-02 is a long-acting IM depot injection of abiraterone decanoate, a novel prodrug of abiraterone delivered through the lymphatic system. PRL-02 potently blocks androgen production with minimal increases in mineralocorticoids or decreases in glucocorticoids through preferential inhibition of Cytochrome P450 (CYP)17 lyase versus CYP17 hydroxylase. Phase 1 is a standard 3+3 design intended to identify a recommended Phase 2 dose (RP2D). PRL-02 is administered every 84 days (1 cycle). As of 9/8/22, 17 pts (6 mCRPC, 11 mCSPC) were treated across 5 dose cohorts (180, 360, 720, 1260, 1800mg). At 720mg and above, 9 of 11 had a 90% reduction in testosterone (T), including 2 pts with T≤ Lower Limit of Quantitation (LLOQ) of 0.1ng/dL. A PSA decline of ≥50% from baseline (PSA50) was observed in 8 of 10pts. PRL-02 was very well tolerated. Only minimal and transient changes in ‘upstream’ steroids (e.g., progesterone) were observed at doses of 1260 mg (the RP2D) and lower. Methods: Phase 2a is an A'Hern single-stage design. Group 1 includes pts with mCSPC divided into 2 groups (1A: previously untreated high-volume disease and 1B: previously untreated, low-volume disease). Group 2 includes pts with mCRPC. Enrollment of 66 pts is planned across 30 sites in the U.S. (NCT04729114). Patient populations, interventions and study design are described below. Clinical trial information: Clinical Trial information: NCT04729114 . [Table: see text]
UP-NEXT (GOG-3049/ENGOT-Ov71-NSGO-CTU): A study of upitifamab rilsodotin (UpRi), a NaPi2b-directed antibody drug conjugate (ADC), in platinum-sensitive recurrent ovarian cancer.
Authors: Richardson Debra L. , Harter Philipp , O'Malley David M. , Gonzalez Martin Antonio , Herzog Thomas J. , Rogalski Caroline , Lemming Rita , Keeton Erika , Burger Robert Allen , Mirza Mansoor Raza 
Published: June 2023

TPS5614 Background: UpRi is a first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC) with limited expression in healthy tissues. It is estimated that the majority of HGSOCs have high NaPi2b expression. Studies are being conducted to evaluate UpRi safety and efficacy in platinum-resistant ovarian cancer (PROC), but there remains an unmet need in the maintenance setting for patients with recurrent platinum-sensitive ovarian cancer (PSOC), particularly for patients who have received prior maintenance therapy, are at high-risk of early relapse, and where close monitoring after platinum-based therapy would generally be considered preferable. Methods: UP-NEXT is a Phase 3 study evaluating UpRi monotherapy as post-platinum maintenance treatment in recurrent PSOC, enrolling patients with NaPi2b-positive tumors (defined as TPS ≥75). Patients must have received 2-4 prior lines of platinum containing chemotherapy, achieved a partial or complete response in their penultimate platinum regimen, and progressed >6 months after completion of the last dose of platinum in the penultimate regimen. Patients may be enrolled if their best response to the last line of treatment is no evidence of disease, complete or partial response, or stable disease. Prior PARPi treatment is required for patients with a BRCA mutation. Patients who received bevacizumab in combination with their most recent platinum containing regimen are excluded. Patients are randomized 2:1 to UpRi 30mg/m2 or placebo, given IV Q4W. The primary endpoint is PFS assessed by BICR, with key secondary endpoint of OS. UP-NEXT is conducted in collaboration with GOG(3049) and ENGOT(Ov71-NSGO-CTU). Approximately 350 patients will be enrolled globally. NCT05329545. Clinical trial information: NCT05329545 .
Uncovering mechanisms of response of pembrolizumab and lenvatinib for the treatment of platinum-resistant high grade serous ovarian cancer.
Authors: How Jeffrey , Westin Shannon Neville , Sims Travis T. , Lito Kathryn , Celestino Joseph , Rangel Kelly M. , Peng Weiyi , Wang Linghua , Jazaeri Amir A. 
Published: June 2023

TPS5619 Background: Despite initial response to conventional platinum-containing therapies, the majority of high grade serous ovarian cancer (HGSOC) patients will eventually develop treatment resistance. Despite interest for immune checkpoint inhibitor alternatives, pembrolizumab monotherapy is poor with objective response rates (ORR) ranging between 4.1 - 10%. Poor response may be linked to higher expression of immunosuppressive factors (e.g. VEGF, TGF-β) in the tumor microenvironment (TME). In an immunosuppressive TME, monotherapy with PD-1 inhibitors can induce T-cell dysfunction and apoptosis, leading to innate resistance to pembrolizumab. Preclinical studies of other tumors have demonstrated that lenvatinib can improve T-cell activation and reduce the tumor-associated macrophage population and TGF-β/VEGF/FGF-signaling. In HGSOC, mechanisms of resistance to pembrolizumab and whether this resistance can be overcome by the addition of lenvatinib remain unknown. The objective of this investigation is to uncover the immunologic basis and synergistic mechanisms of action underlying clinical efficacy of pembrolizumab and lenvatinib in HGSOC. Specifically, we will evaluate the dynamic changes in proliferative and dysfunctional T-cell populations in the peritoneal TME (p-TME) of HGSOC patients receiving monotherapy with pembrolizumab or lenvatinib followed by combination therapy. Methods: All patients will receive a cycle of monotherapy (pembrolizumab 200 mg IV every 3 weeks or lenvatinib 20 mg po daily) followed by combination therapy (both) up to 35 cycles. Enrolled patients will receive intra-peritoneal port placement for serial peritoneal fluid evaluations (cycle 0 day 1, cycle 0 day 8, cycle 1 day 8, cycle 2 day 1, cycle 3 day 1, cycle 5 day 1, then day 1 of every 3rd cycle) for multichannel flow cytometry and single-cell RNA sequencing. Our primary translational objective is to estimate both the individual and combined effects of pembrolizumab and lenvatinib on T-cell dysfunction (PD1+ CD38+) and proliferation (ki67+) in the p-TME using multichannel flow cytometry on the peritoneal fluid. Secondary clinical objective is ORR. Secondary translational objectives include individual and synergistic effects of monotherapy and combination therapy on T-cell effector function, T-cell memory, and myeloid cell subpopulations. Exploratory objectives include evaluating the dynamic changes in immune and non-immune cells in the p-TME for exceptional responders and non-responders using single cell RNA sequencing. Key eligibility criteria include 1) histologic diagnosis of high grade serous ovarian, peritoneal, or fallopian tube cancer 2) platinum-resistant disease and 3) no prior lenvatinib therapy. The trial is open with 10 patients enrolled at the time of submission. Clinical trial information: NCT05114421 .
Oregovomab and non-platinum chemotherapy in PARP inhibitor-resistant ovarian, fallopian tube, or primary peritoneal cancer patients not candidates for platinum retreatment: A multicenter, two-cohort, single-arm phase 2 trial (OPERA/KGOG 3065/APGOT-OV6).
Authors: LEE JUNG-YUN , Park Junsik , Choi Chel Hun , Cho Hyun Woong , No Jae Hong , Hong Dae Gy 
Published: June 2023

TPS5621 Background: As PAPR inhibitors (PARPis) are becoming the standard of care option for epithelial ovarian cancer (EOC), PARPi-resistant patients are increasing. Moreover, non-platinum single agent chemotherapy in these patients has been found to elicit poor survival outcomes. Oregovomab, an investigational murine monoclonal antibody directed against CA-125, has shown promising efficacy in the previous phase II study of combinational front-line adjuvant chemotherapy. The aim of the present study is to investigate the efficacy of oregovomab + non-platinum-based chemotherapy in PARPi-resistant EOC patients not suitable for platinum-based therapy. Methods: OEPRA is a multi-centre, investigator-initiated, two-cohort, single-arm phase II trial recruiting PARPi-resistant EOC patients from five sites in South Korea. The trial includes patients with recurrent EOC who have experienced disease progression despite treatment with PARPis and who have either received bevacizumab or are not eligible for bevacizumab treatment. Mucinous histology type is excluded. Patients who have received one to three prior lines of chemotherapy are to be assigned to Cohort 1 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + pegylated liposomal doxorubicin [PLD] 40 mg/m2 q4w, n = 28), while patients who have received more than three prior lines of chemotherapy are to be assigned to Cohort 2 (oregovamab 2 mg [C1,2,3,5,7 for five doses] + weekly paclitaxel 80 mg/m2 [D1,8,15 q4w], n = 28). A total of 56 patients will be recruited and treated with oregovomab + PLD / weekly paclitaxel until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint is objective response rate by RECIST 1.1. Accrual is expected to be completed in 2023, followed by presentation of results in 2024. The study is registered with Clinicaltrials.gov (NCT05407584). Clinical trial information: NCT05407584 .
A phase II, randomized, double-blind study of the use of rucaparib vs placebo maintenance therapy in metastatic and recurrent endometrial cancer.
Authors: Corr Bradley , Haggerty Ashley Ford , Taylor Sarah E. , Gysler Stefan , Morgan Mark Aloysuis , Behbakht Kian , Lefkowits Carolyn , Alldredge Jill , Brubaker Lindsay , Hopp Samantha , Guntupalli Saketh R 
Published: June 2023

TPS5626 Background: There are currently no approved maintenance therapies for metastatic and recurrent endometrial cancer, which carries a dismal long-term prognosis. The PARP inhibitor drug class has demonstrated significant clinical benefit as a maintenance therapy for patients with germline/somatic BRCA mutations or homologous recombination deficiency (HRD) in ovarian cancers. However, BRCA mutations are not common in endometrial cancer. Loss of function of the tumor suppressor gene PTEN has been demonstrated in greater than 80% of endometrioid endometrial cancers 1. PTEN loss of function is well known to lead to activation of the PI3K-AKT-mTOR pathway but has also been shown to lead to defects in homologous recombination (HR) DNA repair of double strand breaks 2. Specifically, PTEN silencing leads to decreased RAD51 foci formation. Based on this mechanism, in vitro data on endometrial cancer cell lines has demonstrated sensitivity to PARP inhibitors. Notably, sensitivity of PARP inhibition in PTEN loss of function is independent of microsatellite instability (MSI) 3. Methods: This is a multi-center phase II, placebo controlled, double-blinded study of the use of rucaparib as maintenance therapy in patients with metastatic or recurrent endometrial cancer. A maximum of 138 patients will be randomized 1:1 to receive rucaparib at starting dose of 600mg BID dosing vs. placebo. Standard dose reductions of known toxicities will be followed based on FDA approved indications of rucaparib. Patients will remain on therapy until progression of disease or toxicity induced discontinuation. Eligible patients will have Stage III/IV or recurrent endometrial cancer and must have received one or two prior lines of chemotherapy. All histologic subtypes, including carcinosarcoma will be included. Treatment arms will be stratified on histology, number of lines of prior therapy, and complete vs partial response to prior line of therapy. The primary endpoint is progression free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate (ORR), and toxicity. To date, 79 patients have been enrolled. 1. Mutter GL, Lin MC, Fitzgerald JT, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92(11):924-930. 2. Shen WH, Balajee AS, Wang J, et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell. 2007;128(1):157-170. 3. Dedes KJ, Wetterskog D, Mendes-Pereira AM, et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med. 2010;2(53):53ra75. Clinical trial information: NCT03617679 .
ENGOT-EN20/GOG-3083/xport-EC-042: A phase 3, randomized, placebo-controlled, double-blind, multicenter trial of selinexor in maintenance therapy after systemic therapy for patients with P53 wild-type, advanced or recurrent endometrial carcinoma.
Authors: Vergote Ignace , Mirza Mansoor R. , Coleman Robert L. , Perez-Fidalgo Jose Alejandro , Monk Bradley J. , Valabrega Giorgio , Slomovitz Brian M. , Van Gorp Toon , Moore Kathleen N. , Sehouli Jalid , Cibula David , Levy Tally , Aravantinos Gerasimos , Li Kai , Kalyanapu Pratheek , Makker Vicky 
Published: June 2023

TPS5627 Background: Patients (pts) with first-line metastatic or recurrent endometrial cancer (EC) have a poor prognosis. Selinexor is an oral XPO1 inhibitor, which leads to nuclear accumulation of tumor suppressor proteins, including p53. Selinexor is FDA-approved for use in multiple myeloma and diffuse large B-cell lymphoma, and has shown clinical activity in previously treated, advanced EC. Molecular characterization of EC is critical in directing treatment for advanced and recurrent disease. Of the EC molecular subtypes, TP53 wild type (wt) tumors represent 50% of advanced and recurrent tumors. A recent phase 3 study in maintenance after chemotherapy found that, despite the primary endpoint (PFS) not reaching statistical significance, prolonged PFS of oral once-weekly selinexor versus placebo (13.7 months and 3.7 months, respectively) was observed in a prespecified exploratory subgroup analysis of patients with advanced or recurrent TP53wt EC. Methods: XPORT-EC-042 (NCT05611931) is a Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of selinexor as maintenance therapy in pts with TP53wt advanced or recurrent EC, who have achieved a partial response or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 after completing at least 12 weeks of platinum combination chemotherapy ±immunotherapy for primary stage IV or recurrent disease. Eligible pts must be ≥18 years of age, have histologically confirmed EC, and TP53 wt disease based on NGS sequencing assessed by Foundation Medicine. Pts will be randomized 1:1 with either selinexor 60 mg or placebo once weekly in 28-day cycles until progressive disease, toxicity, or 3 years if in complete response. A total of 220 pts will be enrolled at sites across the United States, Canada, Europe, and Israel. The primary objective is to compare PFS in pts treated with selinexor compared to placebo based on RECIST v1.1 criteria as assessed by the Investigator. Key secondary objective is overall survival. Other secondary objectives are safety, time to first subsequent therapy, time to second subsequent therapy, time from randomization until the second progression event (PFS2), and PFS by a blinded independent central review. Patient enrollment is ongoing. Clinical trial information: NCT05611931 .