bluuebunny/crossref_metadata_2025_split huggingface dataset:
RT-PACE: Phase I/II study of adjuvant whole pelvic hypofractionated radiotherapy for non-metastatic cervical and endometrial cancer.
Authors: Son Christina H. , Suneja Gita , Chipman Jonathan , Cursio John , Al-Hallaq Hania A , Gaffney David K. , Hasan Yasmin 
Published: June 2023

TPS5631 Background: Whole pelvic radiation therapy (WPRT) improves locoregional control in women with high-intermediate and high-risk endometrial cancer. The standard treatment course consists of 25-28 fractions (5-5.5 weeks) of 1.8-2 Gy/fraction, and is delivered using intensity-modulated radiation therapy (IMRT), which allows for superior sparing of normal tissue with a subsequent lower rate of acute and late toxicity compared to less conformal treatment techniques. Moderate hypofractionation (HF, >2 Gy/fraction) has been studied in other disease sites, such as breast and prostate cancer, and is associated with lower or comparable toxicity, improved patient convenience, and greater cost savings compared to standard fractionation. However, HF has not been well-studied in the setting of WPRT for gynecologic cancers. Methods: This phase I/II multi-institutional study evaluates the feasibility, safety, and toxicity profile of HF-WPRT in women with non-metastatic cervical or endometrial cancers who have undergone curative hysterectomy and are recommended adjuvant WPRT by their treating physician. Concurrent chemotherapy is not allowed, but can be administered sequentially prior to or after WPRT. Para-aortic radiation or nodal boosts are not allowed, however vaginal brachytherapy boost is permissible. Phase I is a safety study of increasing dose-per-fraction. All treatment regimens have an approximate biologic effective dose of 53 Gy (α/β =10). A keyboard design is utilized to identify the maximum tolerated dose-per-fraction (MTD), defined in this study as the regimen that is associated with a CTCAE grade 3+ gastrointestinal/genitourinary toxicity rate of ≤10% on the last day of WPRT. There are 3 dose cohorts of increasing dose-per-fraction. Phase II will accrue 64 evaluable patients to HF-WPRT using the MTD determined in phase I. The primary endpoint is to evaluate the change in patient-reported gastrointestinal toxicity from baseline to the last day of WPRT using the EPIC bowel score. The study is powered to compare results to the RTOG 1203 IMRT standard fractionation arm. The phase 1 portion of the study completed accrual; the phase II portion opened in April 2022 with a fractionation of 42.56 Gy in 16 fractions. Secondary endpoints include genitourinary toxicity (EPIC, CTCAE), quality of life (FACT-Cx, PRO-CTCAE), financial toxicity (FACIT-COST), and decision-making (Decision Regret Scale). Pelvic control at 2 years is an exploratory endpoint. Clinical trial information: NCT04683653 .
The RAINBO MMRd-GREEN trial (GCIG/DGOG/ENGOT-EN142): A phase III trial on the addition of adjuvant durvalumab to radiotherapy in patients with high-risk MMRd endometrial cancer.
Authors: Kaya Merve , Horeweg Nanda , Leary Alexandra , Welch Stephen , Kommoss Stefan , Weidner Nicola , Fanfani Francesco , Lorusso Domenica , McGrane John , Van Gorp Toon , Boere Ingrid , Westermann Anneke M. , Heijns Joan B. , Putter Hein , Verhoeven-Adema Karen , Smit Vincent T.H.B.M. , Creutzberg Carien L. , Bosse Tjalling , Kroep Judith R. 
Published: June 2023

TPS5633 Background: The molecular class of endometrial cancer (EC) is both prognostic and predictive in high-risk EC (HREC). The TransPORTEC research consortium showed that patients with MMRd HREC did not benefit from adjuvant chemotherapy added to radiotherapy. MMRd tumors are particularly sensitive to immunotherapy. We hypothesize that adjuvant durvalumab added to standard radiotherapy will increase recurrence-free survival (RFS) in patients with MMRd HREC. Methods: MMRd-GREEN is an international, open-label, randomized phase III trial and part of the RAINBO program (NCT05255653). Eligible patients will be allocated (1:1) to adjuvant durvalumab 1500 mg once every 4 weeks for 1 year combined with radiotherapy or standard radiotherapy alone. The primary endpoint is RFS at 3 years. Secondary endpoints are pelvic, vaginal and distant RFS, EC-specific survival, overall survival, treatment-related toxicity, health-related quality of life and exploratory translational research . Main inclusion criteria include histologically confirmed stage IB/II with (substantial) lymph-vascular space invasion (LVSI) or stage IIIA-C MMRd EC, after hysterectomy and bilateral salpingo-oophorectomy (regardless of lymphadenectomy or sentinel lymph node biopsy) without macroscopic residual disease. Molecular classification must be performed according to the WHO 2020 algorithm. The target accrual is 316 patients, accounting for a total drop-out rate of 12%. This sample size yields 80% power to detect a 13% increase in the 3-year RFS (hazard ratio 0.58) as a result of the addition of durvalumab, with an accrual duration of 48 months and follow-up period of 30 months. No interim analysis is planned; an independent data monitoring committee will routinely monitor recurrences and adverse events. Enrollment: Since August 2022, the trial is open for recruitment in the Netherlands and per February 10th 2023, the first 3 patients have been enrolled. Activation of more international centers is ongoing. Clinical trial information: NCT05255653 .
Phase 2 trial of retifanlimab (anti–PD-1) in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) as first-line treatment in patients with PD-L1–positive recurrent/metastatic squamous cell carcinoma of the head and neck.
Authors: Cohen Ezra E.W. , Le Tourneau Christophe , Schaub Richard , Bartenstein Matthias , Cheng Lulu , Licitra Lisa F. 
Published: June 2023

TPS6104 Background: Anti–PD-(L)1 therapies have improved clinical outcomes in PD-L1+ squamous cell carcinoma of the head and neck (SCCHN). However, many patients either do not respond or develop resistance, partly due to additional immune checkpoint receptors including LAG-3 and TIM-3, which are frequently coexpressed with PD-1 on tumor-infiltrating lymphocytes. In preclinical studies, LAG-3 and TIM-3 blockade showed synergistic activity with PD-1 inhibition, and triple blockade improves T-cell reinvigoration and antitumor efficacy over single/double combinations. Emerging clinical evidence also supports blockade of PD-1, LAG-3, and TIM-3 as a promising combination approach in checkpoint inhibitor–naive patients. This study aims to assess the efficacy and safety of the anti–PD-1 antibody, retifanlimab, in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) antibodies as first-line treatment in PD-L1+ recurrent or metastatic SCCHN. Methods: This randomized, double-blind, multicenter, phase 2 study (NCT05287113) includes patients with previously untreated, recurrent or metastatic, PD-L1+ (combined positive score [CPS] ≥1%) SCCHN and ECOG status of 0 or 1. Approximately 162 patients will be randomized 1:1:1 to receive (1) intravenous (IV) retifanlimab 500 mg every 4 weeks (Q4W) plus placebo controls, (2) retifanlimab plus IV INCAGN02385 350 mg Q2W plus placebo, or (3) retifanlimab plus INCAGN02385 plus IV INCAGN02390 400 mg Q2W. Patients will be stratified at randomization by LAG-3 expression (tumor proportion score ≥5% vs < 5%), PD-L1 CPS (1%-19% vs ≥20%), and human papillomavirus p16 status (positive vs negative; oropharyngeal tumors only). Treatment will be administered in 4-week cycles for up to 2 years. The primary endpoint is progression-free survival (PFS; defined per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1). Secondary endpoints are objective response rate per RECIST v1.1, duration of response, disease control, overall survival, and safety. Sample size calculation is based on a median PFS of 3 months, based on historical data for anti–PD-1 monotherapy in the first-line treatment setting for PD-(L)1+ advanced/metastatic SCCHN. PFS, overall survival, and duration of response data will be analyzed by the Kaplan-Meier method. Patient enrollment is ongoing. Clinical trial information: NCT05287113 .
CCTG HN11: SPECT-CT guided elective contralateral neck treatment (SELECT) for patients with lateralized oropharyngeal cancer—A phase III randomized controlled trial.
Authors: de Almeida John R. , Parulekar Wendy R. , Christopoulos Apostolos , Gauthier Isabelle C , Martino Rosemary , McNiven Andrea , Nichols Anthony C. , Parmar Ambika , Prisman Eitan , Ringash Jolie , Smoragiewicz Martin , Subramaniam Rathan M. , Waldron John , Chinn Steven B. , Bates James Edward , Whelan Kate , Tu Wei , Hosni Ali 
Published: June 2023

TPS6114 Background: Lymphatic mapping identifies neck lymph nodes at risk for cancer spread in patients with lateralized oropharyngeal (OPC) squamous cell carcinoma. We hypothesize that a lymphatic mapping guided approach to radiotherapy (RT) treatment of the contralateral neck will enable safe de-escalation of therapy with acceptable disease control with potential benefits in RT related toxicity, QOL, swallowing function and economics. Methods: HN.11 is a Canadian Cancer Trials Group international multi-centre, non-inferiority randomized phase III trial comparing a lymphatic mapping-guided approach for management of the contralateral neck (experimental) vs. bilateral neck radiation therapy (RT) (control). The primary objective is to determine if a lymphatic mapping-guided approach for management of the contralateral neck has a non-inferior disease-free survival (DFS) compared to bilateral neck RT. Secondary objectives: To compare swallowing related QOL, xerostomia, isolated contralateral neck failure, overall survival, loco-regional failure, distant metastases, RT-related toxicities, patient reported adverse events (PRO CTCAE), gastrostomy tube usage, and economics indicators (resource utilization, lost productivity, financial toxicity, EQ5D). Exploratory objectives: Swallowing function using video fluoroscopic swallow studies, head and neck-cancer specific QOL, patterns of lymphatic drainage, radiomic prediction of contralateral lymphatic drainage, correlation of tumour somatic mutations and ctDNA with disease recurrence. Statistical Design: The target sample size is 510 patients. The experimental arm will be considered non-inferior if the upper limit of the one sided 95% confidence interval (CI) of the estimated hazard ratio (HR) does not exceed 1.46 (non-inferiority margin of 6.5% for 2-year DFS). In the primary intention-to-treat (ITT) analysis, the study has 81% power, with a one-sided type I error rate of 5%, assuming 5 years of accrual, 3-years of follow up to observe 178 DFS events, and a 5% loss to follow up. If non-inferiority is demonstrated in the ITT analysis, a secondary per-protocol analysis will be performed, analyzing those patients treated as per their allocation, with 80% power to detect non-inferiority of the experimental arm assuming a conservative 10% cross-over from the experimental to the control arm (i.e. failed lymphatic mapping). Conduct to Date: Study activation September 29, 2022. First enrollment was February 10, 2023. Supported by Canadian Cancer Society, Canadian Institutes of Health Research, National Cancer Trials Network (NCTN). Clinical trial information: NCT05451004 .
Phase 2 study of bintrafusp alfa in recurrent/metastatic olfactory neuroblastoma.
Authors: Bracken-Clarke Dara Mark , London Nyall R , Mallek Marissa , Cordes Lisa M. , Steinberg Seth M. , Marte Jenn , Strauss Julius , Redman Jason M. , Pastor Danielle M. , Schlom Jeffrey , Gulley James L. , Floudas Charalampos S. 
Published: June 2023

TPS6116 Background: Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a rare malignant tumor of the nasal cavity, believed to arise from the basal cells of the olfactory neurosensory epithelium. ONB is often locally advanced at diagnosis with high rates of spread both locoregionally and systemically. Current therapy for locoregional disease is local resection with adjuvant (chemo-) radiotherapy. Actionable mutations are rare, and treatment options for recurrent or advanced, non-resectable, disease are limited and include off-label combination chemotherapy (most frequently platinum-containing) and somatostatin-directed therapies (ONB expresses somatostatin receptors). These are based on limited data, with response rates poorly characterized. Bintrafusp alfa is a first-in-class, bifunctional TGF-β “trap”/anti-PD-L1 fusion protein. Analysis of ONB has demonstrated both PD-1/PD-L1 (London et al, 2018) and TGF-β ligand expression (Romani et al, 2021). Pre-clinical and clinical data in advanced solid tumors demonstrate enhanced antitumor activity with combination PD-L1/TGF-β blockade, with responses observed independently of high PD-L1 levels (Strauss et al, 2020). Thus, combination PD-L1/TGF-β blockade in ONB is a rational approach in a setting of unmet clinical need. Methods: This study is a Phase 2 single-site, single-arm clinical trial of bintrafusp alfa (1200mg IV every 2 weeks for up to 26 doses) for patients with recurrent or metastatic ONB. Participants must co-enroll to the ONB Natural History study at the NCI (NCT4755205). Patients must not be candidates for local therapy, have received at least 1 line of systemic therapy (including a platinum salt), have RECIST 1.1 measurable disease and have adequate organ function. Prior checkpoint inhibitor therapy is permitted with patients cohorted according to checkpoint exposure; up to 21 checkpoint-naïve and 8 checkpoint-resistant patients will be enrolled. The primary objective is objective response rate by RECIST 1.1 with secondary endpoints including safety and tolerability, duration of response and overall survival; exploratory endpoints include pharmacokinetic analyses, PD-L1 and immune cell correlative analyses. The trial follows a Simon two-stage design, requiring ≥1 response in the first 12 patients. Tumor biopsy at enrollment is optional. Imaging for response assessment is planned for 8-week intervals and PET scan (preferably 68Ga-DOTATATE) will be obtained for all patients at baseline and first restaging, then on an individualized basis per radiology advice. This study is presently open at the NCI with 5 patients enrolled as of January 2023. Clinical trial registry:NCT05012098. Clinical trial information: NCT05012098 .
Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after both neoadjuvant and postoperative adjuvant anti-HER2 therapy: Flamingo-01.
Authors: Patel Snehal , Thompson Jaye , Patel Mira , Daugherty F. Joseph , Rimawi Mothaffar F. 
Published: June 2023

TPS617 Background: GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100. In a prospective, randomized, single-blinded, placebo-controlled, multicenter Phase IIb study, no recurrences were observed in the HER2+ population after 5 years of follow-up, if the patient was treated with GLSI-100, survived, and was followed for more than 6 months ( p = 0.0338). Immunotherapy elicited a potent response measured by skin tests and immunological assays. Of the 146 patients that have been treated with GLSI-100 over 4 clinical trials, GLSI-100 was well-tolerated and no serious adverse events observed were considered related to the immunotherapy. Methods: This Phase III trial is a prospective, randomized, double-blinded, multi-center study. After 1 year of trastuzumab-based therapy, 6 intradermal injections of GLSI-100 or placebo will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years for a total of 11 injections over 3 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up for a total of 4 years following the first year of treatment with trastuzumab-based therapy. Patients will be stratified based on residual disease status at surgery, hormone receptor status and region. Approximately 498 patients will be enrolled. To detect a hazard ratio of 0.3 in invasive breast cancer free survival (IBCFS), 28 events will be required. An interim analysis for superiority and futility will be conducted when at least 14 events have occurred. This sample size provides 80% power if the annual rate of events in placebo patients is 2.4% or greater. Up to 100 non-HLA-A*02 subjects will be enrolled in an open-label arm. The patient population is defined by these key eligibility criteria: HER2/neu positive and HLA-A*02; residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy; exclude stage IV; completed at least 90% of planned trastuzumab-based therapy. Trial objectives were to determine if GP2 therapy increases IBCFS, to assess the safety profile of GP2 and to monitor immunologic responses to treatment and assess relationship to efficacy and safety. The study has been initiated at a number of sites in the US. The study is also expected to be opened in Spain, Germany, and France. Clinical trial information: NCT05232916 .
Selective avoidance of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with HER-2 positive/triple negative breast cancer: Prospective, multi-center, single-arm study (ASLAN).
Authors: Ryu Jai Min , Han Wonshik , Lee Han-Byoel , Ahn Sung Gwe , Kim Hee Jeong , Park Hyung Seok , Choi Ji Soo , Kim Haeyoung , Lee Jeong Eon 
Published: June 2023

TPS624 Background: According to advanced neoadjuvant chemotherapy (NACT), which dual HER2 blockage in HER2+ BC and adding carboplatin or immunotherapy in triple-negative breast cancer (TNBC) increased pathologic complete response (ypCR) rates up to 68% and 80%. Because ypCR patients showed better survival, the indications for NACT have expanded to early BC and the expected ypCR rate has increased. Therefore, it may be reasonable to consider omitting surgery in cases with excellent responses to NACT. Several recent retrospective studies and pilot prospective studies have reported axillary pathologic complete response (ApCR) is highly correlated with breast pathologic complete response (BpCR) in HER2+ or TNBC after NACT. The current report describes the design of omission of sentinel lymph node biopsy (SLNB) after NACT in HER2+ or TNBC patients with excellent response. Similarly, EUBREAST-01 (NCT04101851) study is ongoing omission of sentinel lymph node biopsy (SLNB) after NACT in HER2+/TNBC with radiologic complete remission and a BpCR. Methods: The ASLAN trial is a prospective, multicenter, single-arm, clinical study. Five tertiary care hospitals in South Korea are participating. Inclusion criteria: women aged 20-69; cT1-3N0-1M0; HER2+ or TNBC (defined by ER-negative (< 10% positive cells in IHC) and PgR-negative (< 10% positive cells in IHC)); expected complete remission at physical examination and radiological expected Tumor size ≤ 2cm or non-mass enhancement ≤ 4cm at breast MRI after standard NACT; planned breast conserving surgery (BCS) with whole-breast irradiation; ECOG performance status 0-1. Exclusion criteria: SLNB before NACT; previous axillary surgery; bilateral BC. Patients who are eligible proceed BCS. After BCS, patients who showed BpCR are enrolled with omission of SLNB. Patients with no BpCR proceed with routine axillary surgery. The assumption for acceptable 5-year RFS ≥84% is based on previous study findings. The calculated total case number for per- protocol analysis is N=178. Primary endpoint: 5-year recurrence free survival. Secondary endpoint: local recurrence free survival, breast cancer specific survival, overall survival, ipsilateral axillary recurrence interval, distant metastasis free survival, contralateral breast free survival, re-operation rate according to breast biopsy after NACT, adverse event, and quality of life. The first patient was enrolled on September 2021. Among 147 patients who screened, 106 patients have been enrolled in January 2022. We plan to complete the target accrual by December 2025. Clinical trial information: NCT04993625 .
Tailored axillary surgery (TAS) in patients with clinically node-positive breast cancer in the upfront surgery setting: A prospective, single-arm, multicenter trial.
Authors: Terata Kaori , Sagara Yasuaki , Shien Tadahiko , Sakai Takehiko , Takayama Shin , Kitagawa Dai , Iwatani Tsuguo , Tsukioki Takahiro , Ogita Mami , Sanuki Naoko , Yoshida Masayuki , Tsuda Hitoshi , Yamamoto Seiichiro , Iwata Hiroji 
Published: June 2023

TPS628 Background: Axillary lymph node dissection (ALND), which can induce lymphedema, has been omitted in clinically node-negative(cN0) patients with positive sentinel lymph nodes (SLNs) if they meet the eligibility criteria of ACOSOG Z0011. Furthermore, the omission of ALND has been attempted through targeted axillary dissection (TAD) in patients whose cN+ status converts to ycN0 after neoadjuvant chemotherapy. However, ALND remains the standard of care in patients with cN+ who undergo upfront surgery. The aims of this trial are to establish a surgical method of tailored axillary surgery (TAS), which combines TAD and SLN biopsy among patients with cN+ who undergo upfront surgery, and to determine the appropriate criteria for a Phase III TAS trial. Methods: We have planned a single-arm Phase II trial to confirm the feasibility and assess patient eligibility for TAS. A total of 300 patients will be enrolled from 33 study sites in Japan. The eligibility criteria are as follows: 1) histologically-proven invasive breast cancer, 2) upfront surgery is planned, 3) pathologically-diagnosed metastatic lymph node (cytology or core needle biopsy), 4) 1-3 LN metastases in level I by imaging, 5) cT1-3, and 6) females aged ≥18 and ≤74 years on the enrollment date. TAS involves removing marking lymph nodes by TAD (clip, wire, or tattoo) and SLNB, and ALND up to Level II are performed after TAS. These LNs are defined as non-TAS LNs. The primary endpoint is the non-TAS LNs positive rate. Clinicopathological factors (the number of suspected metastases by imaging, the number of metastases in LNs resected by TAS, tumor size, and invasive ductal/lobular carcinoma) are analyzed to predict the non-TAS LN metastasis rate (e.g., < 10%). By using these clinicopathological factors, we determine the eligibility of TAS to omit ALND safely. The secondary endpoints are TAS LNs identification rate, labeled LNs identification rate, marked lymph node resection rate, arm edema incidence rate, and QOL (FACT-B, QuickDASH). After this feasibility study, we will conduct a phase III trial that omits ALND using TAS to investigate the regional recurrence rate.