bluuebunny/crossref_metadata_2025_split huggingface dataset:
NSAB C-14: CORRECT-MRD II—Second colorectal cancer clinical validation study to predict recurrence using a circulating tumor DNA assay to detect minimal residual disease.
Authors: Salem Mohamed E. , Huggins-Puhalla Shannon Leigh , George Thomas J. , Allegra Carmen Joseph , Palomares Melanie R. , Baehner Frederick L , Wolmark Norman 
Published: June 2022

TPS3632 Background: Patients (pts) with stage II and III colon cancer (CC) have unique post-operative decisions regarding adjuvant chemotherapy (ACT). There is a subset of stage II pts with defined clinicopathologic features associated with poor prognosis who may benefit from ACT, although more discriminating and objective predictors of benefit are needed. In addition, there may be a subset of Stage III CC pts who could tolerate a de-escalation of ACT or who may require intensification of ACT to improve clinical outcome. Detectable ctDNA after resection of early-stage solid tumors has been associated with very high risk of recurrence, suggesting ctDNA is evidence of minimal residual disease (MRD). Several studies are ongoing to investigate the role of ctDNA in the optimal management of pts with CC using different assay technologies. Methods: This is a prospective, observational, multicenter study in the United States and Canada of 750 pts who have undergone complete surgical resection for stage II or III CC, have FFPE tissue available from the primary resection sufficient for a novel bespoke MRD assay, and are willing to provide serial whole blood specimens for ctDNA analysis. Subjects are asked to provide study specimens at baseline, pre-recurrence follow-up, and clinical recurrence (if applicable) study visits. ctDNA will be analyzed with an NGS-based MRD assay that identifies somatic genetic alterations from DNA derived from the pt’s tumor tissue, subtracts germline variants, and detects a subset of these tumor-specific (bespoke) ctDNA in the pt’s blood. The primary objective is to validate the association of post-definitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI). Further objectives are to assess the: sensitivity and specificity of ctDNA positivity for subsequent clinical recurrence; contribution of post-surgery baseline, post-adjuvant therapy, and pre-recurrence follow-up ctDNA results on RFI; time from positive ctDNA to clinical recurrence in subjects who had a positive ctDNA result; and compare the Oncotype Colon Recurrence Score estimate of 3 yr recurrence risk with the observed 3 yr recurrence rate. The primary analysis will use a Cox proportional hazards regression applied to the RFI with ctDNA result (positive or negative) measured at post-surgical baseline (or end of ACT if ACT was used) and serially after that as a single, time-dependent covariate. Protocol: 16-002/NSABP C-14. Support: NSABP Foundation. Clinical trial information: 05210283.
SEAMARK: Randomized phase 2 study of pembrolizumab + encorafenib + cetuximab versus pembrolizumab alone for first-line treatment of BRAF V600E-mutant and microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).
Authors: Kopetz Scott , Bekaii-Saab Tanios S. , Yoshino Takayuki , Chung Chin-Hee , Zhang Xiaosong , Tabernero Josep 
Published: June 2022

TPS3634 Background: Among patients with MSI-H/dMMR CRC, BRAF mutations occur in approximately 30%. MSI-H/dMMR and BRAF mutations are both associated with poor prognosis; in patients who have both biomarkers, poor prognosis is thought to be driven by the BRAF mutation. Pembrolizumab is indicated for the treatment of patients with MSI-H/dMMR unresectable or metastatic CRC (mCRC). The BRAF inhibitor encorafenib, in combination with cetuximab, is indicated for previously treated patients with BRAF V600E-mutant mCRC. Currently, there are no first-line treatment options indicated specifically for patients with both MSI-H/dMMR and BRAF V600E-mutant mCRC. To assess the safety and efficacy of combining pembrolizumab with encorafenib + cetuximab, the SEAMARK study (NCT05217446) will evaluate this combination vs pembrolizumab alone in patients with previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC. Methods: SEAMARK is an open-label, multicenter, randomized, phase 2 study. Approximately 104 patients (randomized 1:1; stratified by Eastern Cooperative Oncology Group Performance Status [ECOG PS] 0 vs 1) will receive either pembrolizumab + encorafenib + cetuximab or pembrolizumab. Enrolled patients must be aged ≥16 or ≥18 years (per country-specific regulations) and have previously untreated BRAF V600E-mutant MSI-H/dMMR mCRC; measurable disease (Response Evaluation Criteria in Solid Tumors v1.1); ECOG PS 0 or 1; and adequate bone marrow, hepatic, and renal function. Patients who received prior treatment with BRAF/EGFR inhibitors or immune checkpoint inhibitors, or who have brain metastases (unless radiologically stable) or RAS mutation (or unknown RAS status), will be excluded. The primary endpoint is investigator-assessed progression-free survival. Secondary endpoints include safety and tolerability, overall survival, objective response rate, duration of response, and quality of life. Enrollment will begin in April 2022. Clinical trial information: NCT05217446.
TALENTop: A multicenter, randomized study evaluating the efficacy and safety of hepatic resection for selected hepatocellular carcinoma with macrovascular invasion after initial atezolizumab plus bevacizumab treatment.
Authors: Sun Hui-Chuan , Shen Feng , Liu Lianxin , Huang Zhi-Yong , Song Tianqiang , Kuang Ming , Xiang Bang-De , Bai Xueli , Zhu Xiaodong , Zhou Jian , Fan Jia 
Published: June 2022

TPS4175 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion are consistently considered to be at an advanced stage of disease. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has been the new standard-of-care for those patients. In patients responding to systemic therapy, hepatic resection may provide additional benefit. Here we propose a phase 3 study to investigate whether hepatic resection following atezo/bev can bring more benefits for HCC patients with macrovascular invasion when compared with atezo/bev alone. Methods: This is a multicenter, open-label, two-arm, randomized study designed to evaluate the efficacy and safety of surgical resection plus peri-operative atezo/bev compared with regular systemic atezo/bev (Q3W, every three weeks) in HCC patients with macrovascular invasion and without extrahepatic metastasis. Initially eligible patients have enrolled into induction phase, during which they receive 3 cycles of atezo/bev and 1 cycle of atezo alone as primary systemic therapy. Patients who are assessed as partial response or stable disease (RECIST v1.1 criteria) and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection with post-operative atezo/bev for 1 year (or until loss of clinical benefit or intolerable toxic effects), or Arm B, continuing atezo/bev for 1 year (or until loss of clinical benefit or intolerable toxic effects). The primary endpoint of this study is time-to treatment failure (TTF), defined as time from randomization to the first documented treatment failure (i.e., tumor recurrence or metastasis [Arm A], disease progression [Arm B] according to RECIST v1.1, or death from any cause). We hypothesize that hepatic surgery with peri-operative atezo/bev will improve the TTF from 5.8 months to 9.2 months, with the hazard ratio of 0.63. With 2-sided significance level of 0.05, the sample size for randomization will be 198. The study, registered with clinical trial ID of NCT04649489, started enrollment in Apr 2021. As of Jan 2022, 65 patients have been enrolled and 15 patients have been randomized. Research funding: Shanghai Roche Pharmaceuticals Ltd. Clinical trial information: NCT04649489.
Randomized controlled trial of the efficacy of lymph node dissection on stage IIICr of cervical cancer (CQGOG0103).
Authors: He Misi , Zhong Lin , Wang Haixia , Tang Ying , Zhou Qi , Zou Dongling 
Published: June 2022

TPS5604 Background: In FIGO 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopically positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. No prospective study reported that resecting macroscopic nodes before Concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer. The CQGOG0103 study is a national, prospective, multicenter and randomized clinical study evaluating lymph node dissection on stage IIICr of cervical cancer. Methods: Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by CT/MRI/PET/CT) and the short diameter of image-positive lymph node ≥15mm. 452 patients will be equally randomized to receive either CCRT (Pelvic EBRT/Extended-field EBRT + cisplatin (40mg/m2) or carboplatin (AUC = 2) every week for 5 cycles + brachytherapy) or Open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. The sample size calculation of 346 patients provides 80% power to detect a difference in survival at the two-sided 5% significance level using the log-rank test, considering a 20% reduction, a total of 452 patients are required. This study began in January 2021 and will be accrued within 4 years. Enrollment is ongoing.
A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H-positive triple-negative breast cancer.
Authors: Rugo Hope S. , Cortes Javier , Xu Binghe , Huang Chiun-Sheng , Kim Sung-Bae , Melisko Michelle E. , Nanda Rita , Sharma Priyanka , Schwab Richard , Hsu Pei 
Published: June 2022

TPS611 Background: Adagloxad simolenin (A-S) is an anti-Globo H immunogen comprised of the carbohydrate tumor antigen Globo H, covalently linked to keyhole limpet hemocyanin, a carrier protein that deploys T cells to enhance the humoral response. Administration of A-S in combination with the immune adjuvant OBI-821 serves as an anti-tumor associated carbohydrate antigen vaccine intended to generate anti-Globo H humoral responses in patients with Globo H-expressing tumors. Methods: Study OBI-822-011, a phase 3 study, was initiated in 2018. Following feedback from investigators and advisors the study design was changed from a double-blind, placebo-controlled study to an open-label, standard of care (SOC) study. The revised protocol includes patients who have recovered from surgery and completed all planned neoadjuvant and/or adjuvant multiagent chemotherapy and/or radiation therapy. SOC in the A-S/OBI-821 arm is concomitant therapy of capecitabine or immune checkpoint inhibitor. In the SOC arm patients will receive SOC therapy consisting of observation alone, or adjuvant capecitabine alone, or immune checkpoint inhibitor alone. The key protocol changes included a change from open-label to standard of care, providing unblinding and reconsent guidelines for patients enrolled into the study prior to the protocol amendment, allowing concurrent adjuvant single agent chemotherapy, revising the stratification algorithm from a non-hierarchical to a hierarchical structure and aligning the stratification factors with prognostic factors more representative of the study population, revising the eligibility criteria, number and frequency of assessments to reduce patient burden, revising the interim analysis timepoints for futility, and removed an interim analysis for superiority. Study Objectives: Primary Objective: To determine the effect of A-S/OBI-821 treatment on improving IDFS in the study population. Secondary Objectives: To determine the impact of A-S/OBI-821 treatment on Overall survival (OS), Quality of life (QoL), Breast cancer-free interval (BCFI), Distant disease-free survival (DDFS) in the study population; To determine the safety and tolerability of A-S/OBI-821 in the study population. Key Exploratory Objectives: Beyond the safety, efficacy, and QoL endpoints of this trial, exploratory endpoints will evaluate the relationship between aberrant Globo H expression and baseline characteristics, including tumor pathology and immune factors. Conclusion: An estimated 668 subjects will be enrolled, treated for up to 2 years, and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NCT03562637.
NANORAY-312: A phase III pivotal study of NBTXR3 activated by investigator’s choice of radiotherapy alone or radiotherapy in combination with cetuximab for platinum-based chemotherapy-ineligible elderly patients with locally advanced head and neck squamous cell carcinoma.
Authors: Le Tourneau Christophe , Hoffmann Caroline , Takacsi-Nagy Zoltan , Liem Xavier , Salas Sébastien , Debard Anais , Finzi Laetitia , Farber Leonard A , Gogishvili Miranda , Kristesashvili Giorgi , Makharadze Tamta , Yom Sue S. 
Published: June 2022

TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are largely underrepresented in clinical trials (CT). Broad access to CTs in this population is challenging due to an increased prevalence of comorbidities and ageing-related conditions. However, as population-age increases, more and more elderly patients are diagnosed with LA-HNSCC although many are not eligible to receive standard cisplatin-based concurrent chemoradiation (CRT). CRT-related toxicities, treatment burden and compliance are a concern. NBTXR3, a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral injection and activated by radiotherapy (RT). NBTXR3 is designed to locally amplify the tumor-killing effect of radiotherapy without additional toxicity to surrounding healthy tissue. NBTXR3 has been shown to prime the adaptive immune response in cancer models. NBTXR3 obtained EU marketing approval in preoperative treatment of locally advanced soft tissue sarcomas. In a Phase I trial of NBTXR3 + RT alone in elderly LA-HNSCC patients, the combination was shown to be safe and an Objective Response Rate (ORR) of 85.4% and CRR of 51.2% was reported at ASTRO 2021. A pivotal randomized phase III study was initiated and is now recruiting. Methods: NANORAY-312 [NCT04892173] is a global, open-label, randomized (1:1), 2-arm, Investigator's choice Phase III (Pivotal Stage) study to investigate the efficacy and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly patients with LA-HNSCC. 500 patients will be enrolled. Eligible patients are ≥65 years with at least one measurable (RECIST 1.1) biopsy-confirmed T3-4 (AJCC v8) SCC of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx which is amenable for intratumoral injection. For patients with oropharyngeal cancer, human papilloma virus (HPV) status must be known. In addition to the primary tumor, a single accessible LN in the neck is eligible for intranodal injection. The primary objective is PFS. The key secondary endpoint is OS. Other secondary endpoints include ORR, safety and tolerability and quality of life. Enrollment began in January 2022 and is ongoing. Clinical trial information: NCT04892173.
Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open-label randomized phase II trial.
Authors: McArthur Heather L. , Leal Jorge Henrique S. , Page David B. , Abaya Christina DiLauro , Basho Reva K , Phillips Michelle , Chan David , Hool Hugo , Park Dorothy J. , El-Masry Mary , McAndrew Philomena , Sikaria Swati , Spring Laura , Bardia Aditya , Tighiouart Mourad , Dadmanesh Farnaz , Giuliano Armando E. , Shiao Stephen Lawrence 
Published: June 2022

TPS624 Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: 174 patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer will be randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion including radiotherapy per local clinical standard. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Clinical trial information: NCT03747120.
Emotion and symptom-focused engagement (EASE): A multisite randomized controlled trial of an intervention for individuals with acute leukemia.
Authors: Fitzgibbon Kyle , Malfitano Carmine , Rydall Anne , Hannon Breffni , Richardson Harriet , Schimmer Aaron David , Zimmermann Camilla , Rodin Gary 
Published: June 2022

TPS7072 Background: Acute leukemia (AL) is characterized by rapid symptom onset requiring urgent hospitalization and initiation of intensive treatment with high mortality. Despite this, there is scant research on its psychological and physical impacts and even less on interventions to alleviate them [Bryant 2016]. We conducted a longitudinal study showing substantial physical and psychological distress in these patients [Rodin 2013; Zimmermann 2013; Nissim 2013; Nissim 2014; Gheihman 2016; Rodin 2018a; Shaulov 2019]. Despite this distress, we observed a lack of referrals for specialized psychosocial and palliative care. Based on these findings, we developed an integrated psychosocial and early palliative care (symptom control) intervention, Emotion And Symptom-focused Engagement (EASE), for AL [Rodin 2015]. In a subsequent randomized phase II trial of EASE in patients newly diagnosed with AL, we demonstrated its feasibility and found preliminary evidence that it reduces physical and psychological distress compared to usual care [Rodin 2020]. EASE includes: i) an 8-week manualized psychotherapy intervention tailored to AL to prevent and treat psychological symptoms through: supportive counselling and trauma-focused cognitive-behavioural therapy; and emotional assessment and affect modulation; ii) 4-week systematic screening of physical symptoms with automatic referrals to palliative care for the management of moderate to severe symptoms. Methods: We are conducting a multi-centre randomized controlled phase III trial of 266 AL patients comparing EASE to usual care in collaboration with the Canadian Cancer Trials Group at Princess Margaret Cancer Centre, Sunnybrook Health Sciences, Kingston Health Sciences and the Ottawa Hospital in Ontario, Canada. Patients are newly diagnosed with acute myeloid leukemia or acute lymphoblastic leukemia and randomized within two weeks of hospital admission for induction chemotherapy with curative intent. Patients randomized to EASE will receive psychological support from a trained mental health clinician for 8 weeks and will be assessed for physical symptoms twice weekly until discharged from hospital. Moderate to severe physical symptoms will trigger a referral to a symptom-control team for symptom management. The symptom-control team consists of a physician and nurse with expertise in symptom control and other professionals as needed. All participants will be assessed for physical symptom severity, psychological distress, quality of life and satisfaction with care at baseline, 4, 8, 12 weeks, 6 and 12 months. Hypotheses will be tested using multilevel modeling (MLM) with maximum likelihood estimation, conducted as intention-to-treat analyses. The DMC last reviewed the trial in April 2021 and suggested that the trial continue as planned. Clinical trial information: NCT04224974.