bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II study of stereotactic radiosurgery with concurrent olaparib followed by adjuvant durvalumab and physician’s choice systemic therapy in patients with breast cancer brain metastases.
Authors: Shen Colette , Abdou Yara , Chen Linda , Tan Xianming , Gupta Gaorav P. , Lynce Filipa , Lobbous Mina , Stringer-Reasor Erica Michelle , Anders Carey K. 
Published: June 2023

TPS1133 Background: Despite progress in the treatment of brain metastasis for HER2+ breast cancer, outcomes for patients with HER2-negative breast cancer brain metastases remain poor. Current standard of care consists of local therapies, including surgery and radiotherapy, followed by systemic therapy. Preclinical studies show inhibitors of poly(ADP-ribose) polymerase (PARP) are effective in combination with radiation therapy as a DNA damage response inhibitor. Triple-negative breast cancer (TNBC) has higher rates of homologous recombination deficiency compared to other breast cancer subtypes, and together with HER2-negative, BRCA-mutated breast cancer would be particularly sensitive to PARP inhibition. PARP inhibition has also demonstrated promising efficacy combined with immunotherapy in patients with germline BRCA-mutant and metastatic TNBC in clinical trials (MEDIOLA, TOPACIO). In addition, immunotherapy with stereotactic radiosurgery (SRS) is associated with favorable intracranial control and survival in patients with brain metastases. We hypothesize that this biologically-driven combination will enhance local control of SRS-treated brain metastases through synergy with PARP inhibition, while controlling micrometastatic disease in the brain and extracranial sites via potentiation of the immune response. Methods: We are conducting a multi-institution, Phase I/II trial of SRS plus olaparib, followed by durvalumab (with physician’s choice systemic therapy), for patients with TNBC (any BRCA status) or HER2-negative with BRCA-mutated (germline or somatic) breast cancer brain metastases [NCT04711824]. A total of 41 patients are planned for enrollment at 8 sites. The primary objectives are to evaluate safety and tolerability (Phase I) and determine intracranial disease control at 6 months (Phase II) of this treatment combination. Secondary objectives include determining clinical activity via intracranial and global progression-free survival, overall survival, and intracranial and extracranial response rate. Exploratory objectives will assess potential biomarkers of treatment response, including changes in circulating tumor cells and DNA in blood and cerebrospinal fluid, germline and tumor mutations in DNA repair pathway genes, and PD-L1 expression, as well as quality of life and patient-reported outcomes. A surgical sub-study (n=5) will evaluate olaparib concentration/distribution in resected brain metastases. As of January 2023, cohort 1 of phase I has been completed without dose-limiting toxicity. Clinical trial information: NCT04711824 .
A randomized, open-label, phase 2 study evaluating abemaciclib in combination with irinotecan and temozolomide in participants with relapsed or refractory Ewing sarcoma.
Authors: VAN HAL Gertjan , Rubio-San-Simón Alba , Ogawa Chitose , Juan-Ribelles Antonio , Knoderer Holly , Lewin Jeremy Howard 
Published: June 2023

TPS11580 Background: Ewing’s sarcoma (ES) is the second most common malignant bone tumor affecting children and young adults. Patients with relapsed disease have a poor prognosis and need effective therapies. EWS-FLI1, the most common ES fusion gene (90-95% of cases), is an oncogenic transcription factor that downregulates intrinsic cyclin-dependent kinase (CDK) inhibitors, CDKN1A and CDKN1C, which promote cell cycle arrest and upregulates CDK4, which drives entry into the cell cycle. This provides a biological rationale for the clinical evaluation of CDK4/6 inhibitors in ES. Abemaciclib is a selective CDK4/6 inhibitor approved for the treatment of breast cancer. It is approximately 14 times more potent against CDK4/cyclin D1 than CDK6/cyclin D3 in enzymatic assays and has the advantage of continuous dosing schedule without breaks for neutrophil recovery. Abemaciclib is currently also in clinical development for paediatric patients with relapse/refractory solid tumors in combination with irinotecan and temozolomide (JPCS study, NCT04238819). This study, NCT05440786, will evaluate the potential benefit of adding abemaciclib to irinotecan plus temozolomide for the treatment of relapsed/refractory ES. Methods: This randomized, open-label, Phase 2 study is part of the CAMPFIRE master protocol. It is enrolling paediatric and young adult patients (1–39 years) with relapsed/refractory ES or ES-like tumors. Approximately 45 patients will be randomized 2:1 between 2 arms: irinotecan and temozolomide with or without abemaciclib. Stratification factors include age, pulmonary/non-pulmonary site of metastases, and time to recurrence from initial diagnosis. Patients will receive irinotecan (50 mg/m2/day intravenously) and temozolomide (100 mg/m2/day orally) on days 1-5. Abemaciclib will be administered orally twice-daily on a continuous 21-day cycle. The abemaciclib dose will be 55mg/m2 BID for patients < 18 years and 100mg BID for those ≥18 years. Besides 25 and 50mg tablets, abemaciclib will be available as 2.5mg granules allowing administration of doses as low as 10mg to patients with a body surface area lower than 0.2m2. Treatment continues until disease progression or other discontinuation criteria are met. The primary endpoint is progression-free survival (PFS) determined by a blinded independent review committee using Response Evaluation Criteria in Solid Tumors, Version 1.1. Key secondary endpoints include overall survival, objective response rate, duration of response, disease control rate, PFS determined by investigator assessment, safety, and pharmacokinetics. Additional analysis includes exploratory biomarker testing. This study is open and actively enrolling in Australia, Europe, Japan, and United States. Clinical trial information: NCT05440786 .
ENLIGHten-01: A phase 1 study of fluorescein-specific (FITC-E2)-CAR T cells in combination with folate-fluorescein (UB-TT170) for osteosarcoma.
Authors: Albert Catherine Michelle , Pinto Navin R. , Taylor Mallory , Wilson Ashley , Rawlings-Rhea Stephanie , Huang Wenjun , Seidel Kristy , Narayanaswamy, Prabha , Mgebroff Stephanie , Brown Christopher , Garcia Jacob , Teoh Jeffrey , Gardner Rebecca Alice , Orentas Rimas , Jensen Michael C. , Park Julie R. 
Published: June 2023

TPS11581 Background: Outcomes for relapsed osteosarcoma (OS) remain poor and there are no systemic therapies that have been shown to provide a survival benefit. Chimeric Antigen Receptor (CAR) T cell immunotherapy involves the adoptive transfer of T-lymphocytes that have been engineered to recognize tumor-specific antigens, resulting in targeted lysis of malignant cells. Folate receptors (FR) are membrane-bound surface proteins that bind folates with high affinity. FRs are overexpressed in OS and have very limited expression in normal tissue. UB-TT170 (Umoja Biopharma) is a small molecule bispecific “adapter” consisting of folate conjugated to fluorescein (FL). It penetrates tumors in minutes and is retained for long periods of time due to high affinity for the FR, while unbound UB-TT170 rapidly clears from the blood and from FR- tissues. We hypothesize that administration of fixed dosing anti-FL(FITC-E2) CAR T cells followed by escalating doses of UB-TT170 will deliver personalized immunotherapy to OS patients. In addition, this approach offers an attractive safety mechanism since administration of NaFL should reverse CAR T cell reactivity. Methods: We designed a Phase I study for young adult (15-30 yr) patients with recurrent/refractory OS to examine the safety and feasibility of administering autologous, peripheral blood-derived T cells that have been genetically modified to express a 2nd generation FL-specific CAR in combination with intra-subject dose escalation of UB-TT170. The primary objective is to identify a recommended dose escalation sequence of UB-TT170 to move forward in clinical development. A 3+3 design will be used to investigate 3 possible dosing sequences. The trial opened in July 2022. As of January 5, 2023, 5 subjects have enrolled and one subject has been treated on dose regimen 1.T cell products have been successfully manufactured for all enrolled subjects. The trial remains open to enrollment. Clinical trial information: NCT05312411 .
PEMBROCABOSARC: Combination of pembrolizumab and cabozantinib in patients with advanced sarcomas.
Authors: Sellan-Albert Sabrina , Toulmonde Maud , Spalato Mariella , Bertucci Francois , Bompas Emmanuelle , Desmoulins Isabelle , Duffaud Florence , Cousin Sophie , Auzanneau Celine , Lortal Barbara , Pulido Marina , Le Loarer François , Italiano Antoine 
Published: June 2023

TPS11586 Background: Despite optimal treatment, up to 40% of patients with sarcomas will develop locoregional and/or distant relapse and median survival in this setting is less than two years. There are very few options in the treatment of undifferentiated pleomorphic sarcomas whereas there is no specific treatment regimen established for recurrent osteosarcoma (OSS) and Ewing sarcoma (ES). Innovative strategies are therefore urgently needed in these settings. In preclinical studies, while immune checkpoint inhibitors were insufficient in controlling tumour growth, combining them with M2 macrophage or angiogenesis targeting resulted in superior tumour control (Mao et al, Clin Cancer Res 2016; Zhu et al, Cancer Res 2014). Combining both antiangiogenic and MET inhibition properties, cabozantinib has shown both preclinical and clinical activity, notably in osteosarcoma and Ewing sarcoma (Italiano et al. ESMO 2018). Interestingly, cabozantinib has also recently been shown to trigger an innate immune response in a preclinical model (Patnaik et al, Cancer Discov 2017). Altogether, these findings pave the way for studies assessing the impact of targeting angiogenesis, MET and immune response in soft-tissue and bone sarcomas. Methods: PEMBROCABOSARC (NCT05182164) is a multi-stratum, three single-arm phase 2, multicenter, open-label study investigating pembrolizumab combined with cabozantinib in patients with advanced selected sarcomas: undifferentiated pleomorphic sarcoma (stratum 1), osteosarcoma (stratum 2), Ewing sarcoma (stratum 3). Strata 1 and 2 will enroll ~32 patients and stratum 3 ~55 patients, respectively. Each stratum phase II will be conducted using a Simon's optimal two-stage design. Eligible and consented patients must be ECOG PS 0–1, have measurable and progressive disease according to RECIST 1.1 and have received less than 3 previous lines of systemic therapy for advanced disease and consent also to baseline and per treatment biopsies. Cabozantinib will be administered orally, once daily at a fixed dose of 40 mg, continuously. Pembrolizumab will be administered by intravenous infusion every 3 weeks on Day 1 of each cycle, at a fixed dose of 200 mg. Both treatments will start on Day 1 (of cycle 1). The primary endpoint is 6-months non progression rate as per RECIST 1.1. Secondary endpoints include adverse events (AEs)/serious AEs, best overall response, and progression-free survival. Pharmacodynamic and other biomarkers will be explored on blood and tumor tissue. The first patient received study drug on May, 31, 2022; 8 of planned 119 patients have been enrolled and 5 sites across France among the planned 10, are currently enrolling patients. Clinical trial information: NCT05182164 .
SARC041: A phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma.
Authors: Dickson Mark Andrew , Ballman Karla V. , Weiss Mia C. , Attia Steven , Wagner Michael J , Pollack Seth , Choy Edwin , Wagner Andrew J. , Wilky Breelyn A. , Davis Lara E. , Riedel Richard F. , Tap William D. 
Published: June 2023

TPS11587 Background: Recurrent or metastatic dedifferentiated liposarcoma (DDLS) remains a difficult disease to treat. Available agents such as doxorubicin, eribulin, trabectedin, ifosfamide, dacarbazine, or gemcitabine-based regimens are associated with low response rates and only modest improvements in progression free or overall survival. The oncogene CDK4 is ubiquitously amplified in this disease and represents a rational therapeutic target. In single-arm phase 2 studies, treatment with selective CDK4 inhibitors resulted in clinical benefit (12-week progression-free survival (PFS) of 57% with palbociclib and 74% with abemaciclib). We hypothesize that treatment with abemaciclib will improve PFS compared to placebo in patients with recurrent or metastatic DDLS. Methods: This is a phase 3 randomized double-blind study of abemaciclib versus placebo. Eligible patients have recurrent or metastatic dedifferentiated liposarcoma (purely well-differentiated liposarcoma excluded), progression of disease by RECIST 1.1 in the 6 months prior to study entry, any number of prior systemic therapies, and adequate organ function and performance status. Patients are stratified by number of prior lines of therapy (0 vs 1 or more) and randomized 1:1 between abemaciclib 200 mg PO twice a day and matching placebo. Patients are followed with scans every 6 weeks (every 12w after 36w) and those with progression of disease on placebo may cross over to open label abemaciclib. The primary endpoint is PFS. Target enrollment is 108 evaluable patients which provides 80% power with two-sided 10% significance level to detect a hazard ratio of 0.6. Secondary endpoints include response rate, PFS and response rate after crossover, and overall survival. Archival tissue will be collected to explore potential biomarkers. As of Feb 1, 2023, 43 patients have been accrued at 9 participating centers. Clinical trial information: NCT04967521 .
Phase 1 dose-expansion study of oral TP-1287, a cyclin-dependent kinase 9 (CDK9) inhibitor, in patients with Ewing sarcoma (EWS).
Authors: Cote Gregory Michael , Wagner Andrew J. , Charlson John A. , Hu James S , Dickson Mark Andrew , D'Amato Gina Z. , Kabir Sujan , Xu Bo , Lebedinsky Claudia , von Mehren Margaret 
Published: June 2023

TPS11589 Background: Cyclin-dependent kinase 9 (CDK9) blockade inhibits tumor growth and progression by impairing the transcription of key oncogenes, such as myeloid cell leukemia-1 (MCL-1) and c-MYC. CDK9 overexpression has been observed in sarcoma patients (pts), and CDK9 has emerged as a potential therapeutic target in pts with sarcoma. TP-1287 is an investigational orally delivered phosphate prodrug of the CDK9 inhibitor alvocidib. In preclinical studies, TP-1287 has been shown to decrease MCL-1 expression and phosphorylation of RNA polymerase II (RPB1), and inhibit tumor growth in an Ewing sarcoma (EWS) mouse model. Phase 1 dose-escalation in solid tumors has completed and TP-1287 is being investigated in a dose expansion cohort in pts with EWS (NCT03604783). The design of the expansion part of the trial in pts with EWS is herein described. Methods: Up to thirty pts with EWS will be enrolled in this dose expansion cohort. Key eligibility criteria are age ≥18 years (≥12 years, if weight ≥40 kg); histologically confirmed locally advanced or metastatic unresectable EWS; received 1 to 5 prior lines of treatment including an anthracycline; one or more measurable tumors per the RECIST v1.1; ECOG performance status of ≤1; acceptable liver and renal function, and acceptable hematologic and coagulation status; no treatment with surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives. Eligible pts will be treated with oral TP-1287 monotherapy RP2D established from the dose escalation part (11 mg BID, continuous dosing in a 28-day treatment cycle) and will continue treatment until treatment-related adverse event or disease progression. Assessments will be performed on Day 1 and Day 15 of each cycle. Tumor response assessment will be done after Cycle 2 and at the end of every other cycle thereafter. The primary objectives are objective response rate (ORR) and clinical benefit rate (CBR) ; secondary objectives are median progression-free survival (PFS), PFS rate at 16-weeks and 24-weeks and safety; and exploratory objectives include evaluation of systemic exposure and pharmacodynamics. Safety data will be reviewed on an ongoing basis and a Bayesian approach will be used to assess the efficacy data. Statistical analysis for safety and efficacy parameters will be primarily descriptive in nature. EWS dose expansion cohort is currently recruiting in the United States. Clinical trial information: NCT03604783 .
The FARGO study: Frailty assessment for risk prediction in gynecologic oncology.
Authors: Nguyen Julie My Van , Vicus Danielle , Hogen Liat Frida , Zigras Tiffany , Roldanbenitez Yetiani , Marcucci Maura 
Published: June 2023

TPS12137 Background: Little is known about how to best predict postoperative outcomes and chemotherapy tolerance in an increasingly aging and complex gynecologic oncology (GO) population. Frailty is a multidimensional age-related and disease-related state of vulnerability to stressors due to reduced capacity of different physiological systems. Resource limitations are a barrier to routine adoption of frailty assessments through comprehensive clinical evaluations in daily practice. This highlights the relevance of studying potential biomarkers of frailty, which could complement or replace clinical assessments. Frailty has been associated with worse perioperative and oncologic outcomes in many subspecialties, however the literature in patients with gynecologic malignancies is very limited. Methods: The FARGO study is a multi-centre prospective cohort study of 280 patients aged ≥55 years-old undergoing surgery, with or without chemotherapy for a suspected or confirmed gynecologic malignancy. Patient recruitment will occur over 13 months. The over-arching goal is to evaluate the predictive value of frailty assessments in predicting surgical and chemotherapy outcomes. The two primary objectives are: 1) To evaluate the predictive value of preoperative frailty assessment based on the Frailty Phenotype (FP), compared to a perioperative cardiovascular risk assessment, in predicting the composite of all-cause death or new disability at 6 months after surgery 2) To create of a biobank to explore possible biomarkers of frailty, including mitochondrial DNA levels. Secondary objectives include to evaluate the predictive value of clinical and biomarker frailty assessment for 30-day postoperative complications, for chemotherapy tolerance and 1-year recurrence-free survival. Patients will undergo frailty and cardiovascular risk assessment prior to surgery and/or neoadjuvant chemotherapy. A trained clinical research assistant will measure frailty based on the clinical frailty scale (CFS) and the FP. The cardiovascular risk calculation will be based on the preoperative Revised Cardiac Risk Index, age, and occurrence of myocardial injury after non-cardiac surgery (MINS). Research personnel blinded to the frailty and cardiovascular risk assessment will evaluate study outcomes including death, disability, and clinical events at 30 days, 6 months, and 12 months after surgery. Disability will be measured with the WHODAS 2.0 (World Health Organization Disability Assessment Schedule), a validated patient-reported outcome measure. Pre-specified blood biomarkers will be measured. Our study emphasizes patient-centered outcomes (i.e. loss of independence, short and long-term disability) and system-level outcomes. Our findings may have important implications to assist in risk stratification and planning for oncologic treatments and perioperative care needs. Clinical trial information: will be added later .
A randomized phase III clinical trial of yoga for chemotherapy-induced peripheral neuropathy treatment.
Authors: Saint Kirin , Han Katherine , Piulson Lauren , Seluzicki Christina , Zhi Iris , Bao Ting 
Published: June 2023

TPS12143 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful, and debilitating side effect of many standard chemotherapy regimens. CIPN symptoms include pain, paresthesia, and muscle weakness, and patients may exhibit functional decline and lower quality of life. Our prior study showed more than half of breast cancer survivors experience persistent CIPN up to a mean duration of 5.6 years, which is associated with a doubled fall risk. Identifying non-pharmacological approaches to reduce CIPN symptoms and improve cancer survivors’ outcomes is urgently needed. Yoga is a meditative movement therapy that includes stretching, and flexibility and balance training. Our pilot study (NCT03292328) demonstrated that yoga reduced CIPN-related symptoms, and improved quality of life and functional reach scores compared to waitlist control. We hypothesize that yoga can reduce CIPN symptoms, improve function, and reduce the risk of falls. Methods: We are conducting a three-arm randomized education and usual care-controlled trial in cancer survivors with chronic CIPN pain at Memorial Sloan Kettering Cancer Center (MSK), New York, NY. Participants in the intervention arm will receive twice-weekly one-hour Hatha yoga classes taught virtually by MSK instructors and practice yoga at home daily for eight weeks. Participants in the education control arm will receive one-hour virtual education classes twice per week taught by an MSK instructor for eight weeks. Participants in the usual care arm will continue their usual care for CIPN for eight weeks. The primary endpoint is the Brief Pain Inventory-Short Form average pain item at weeks 8 and 24. Secondary outcomes include the Neuropathic Pain Scale, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, Patient-Reported Outcomes Measurement Information System Global Health, Brief Fatigue Inventory, Insomnia Severity Index, Hospital Anxiety and Depression Scale, Quality of Life Questionnaire of CIPN twenty-item scale, functional assessments, and quantitative sensory testing at weeks 0, 4, 8, 12, 18, and 24. Eligibility criteria include: 1) Moderate-to-severe CIPN pain, defined by a score of 4 or greater on a 0-10 numerical rating scale; 2) completion of neurotoxic chemotherapy at least three months prior; 3) no changes in anti-neuropathy medications within three months of enrollment; and 4) changes in balance and functionality. As of February 2023, we have accrued 64 of our total target of 268 participants. We anticipate completing accrual in March 2025. We have 35 participants in the yoga intervention, 15 participants in education control, and 14 participants in usual care control. The majority (89%) of participants are female and 11% are male. 78% of our participants are white, 16% are black or African American, 1% are Asian, and 5% identify as more than one race. Clinical trial information: NCT05121558 .