bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).
Authors: Morris Van K. , Yothers Greg , Kopetz Scott , Jacobs Samuel A. , Lucas Peter C. , Iqbal Atif , Boland Patrick M , Deming Dustin A. , Scott Aaron James , Lim Howard John , Wolmark Norman , George Thomas J. 
Published: May 2020

TPS4121 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint across all US and Canadian cooperative groups. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103 .
Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin 18.2+/HER2−advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW.
Authors: Shah Manish A. , Ajani Jaffer A. , Al-Batran Salah-Eddin , Bang Yung-Jue , Catenacci Daniel , Enzinger Peter C. , Ilson David H. , Kim Sunnie , Lordick Florian , Shitara Kohei , Van Cutsem Eric , Arozullah Ahsan , Park Jung Wook , Xu Rui-hua 
Published: May 2020

TPS4648 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. Claudin (CLDN)18.2 has emerged as a promising targetable biomarker. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Upon malignant transformation, structural loss in gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Results of a phase 2 study (NCT01630083) showed prolonged survival of patients with CLDN18.2-positive (CLDN18.2+) advanced G/GEJ adenocarcinoma treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone. Methods: This phase 3, double-blind, placebo-controlled study (NCT03653507) will enroll ~500 adult patients from global sites. Patients are required to have CLDN18.2+/HER2− locally advanced unresectable or metastatic G or GEJ adenocarcinoma that is radiographically evaluable per RECIST v1.1. Patients are not permitted to have received prior treatment with chemotherapy for advanced or metastatic G or GEJ adenocarcinoma. Patients will be randomly assigned 1:1 to receive either zolbetuximab plus CAPOX or placebo plus CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at a loading dose of 800 mg/m2 IV on Cycle 1 Day 1 followed by 600 mg/m2 IV every 3 weeks. Central testing of tumor tissue will determine CLDN18.2 and HER2 status (if unknown); patients will be considered CLDN18.2+ if ≥75% of tumor cells demonstrate moderate-to-strong membranous immunohistochemical staining. The primary objective is to compare progression-free survival between treatment arms. Secondary endpoints are overall survival; objective response rate; duration of response; and the safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of January 31, 2020, 127 sites were active and open to enrollment. Clinical trial information: NCT03653507 .
A randomized phase II/III study of paclitaxel/cisplatin versus cisplatin/5-fluorouracil in neoadjuvant chemoradiotherapy (CRT) followed by surgery for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Huang Ta-Chen , Hsu Chih-Hung , Cheng Jason C. , Lin Chia-Chi , Guo Jhe-Cyuan , Kuo Hung-Yang , Hsu Feng-Ming , Huang Pei-Ming , Ko Kuan-Yin , Lee Jang-Ming 
Published: May 2020

TPS4650 Background: Meta-analyses have shown the survival benefit of cisplatin/5-fluorouracil (PF) neoadjuvant CRT over surgery alone for patients with locally advanced ESCC. The CROSS study has demonstrated the statistically significant survival benefit of paclitaxel/carboplatin neoadjuvant CRT for patients with locally advanced esophageal cancer, especially ESCC. A network meta-analysis based on published phase III trials suggested that paclitaxel/platinum might be superior to PF as neoadjuvant CRT in patients with ESCC (Huang et al: Jpn J Clin Oncol. 2015;45:1023–8). However, a direct comparison of two CRT regimens in a prospective randomized clinical trial has not been performed in ESCC. We designed this clinical trial to test the hypothesis that paclitaxel-platinum is superior to PF as neoadjuvant CRT in patients with locally advanced ESCC. Methods: This single center open-label phase 2/3 study randomizes patients with histologically confirmed ESCC, T3/4aN0M0 or T1-3N1-3M0 (AJCC 7th edition), in 1:1 ratio, to receive TP (paclitaxel, 50 mg/m2/week; cisplatin 30 mg/m2/week; for 5 weeks) or PF (cisplatin 75 mg/m2, d1; 5-FU 1,000 mg/m2, d1-4; on week 1 and week 5)-neoadjuvant CRT (180 cGy/d, 5 days/week, for 5 weeks). Esophagectomy will be performed 6 to 10 weeks after completing CRT. All patients must be eligible to esophagectomy, with tumor length ≤8cm and tumor radial ≤5cm, with adequate organ functions, and have ECOG performance status of 0-2. In the phase 2 stage, 128 patients will be enrolled, assuming the pathologic complete response (pCR) rate of TP and PF as 45% and 25%, respectively, with a power of 80% and one-sided 10% significance level. If the primary endpoint of pCR is met, additional 120 patients will be enrolled for the phase III stage with overall survival as the primary endpoint, assuming the hazard ratio of TP versus PF as 0.65 with a power of 80% and a 5% significance level. The trial started patient enrollment in May, 2017. As of Jan of 2020, 52 of planned 128 patients for phase II part have been enrolled. Clinical trial information: NCT03623737 .
A phase II/III study of perioperative nivolumab and ipilimumab in patients (pts) with locoregional esophageal (E) and gastroesophageal junction (GEJ) adenocarcinoma: A trial of the ECOG-ACRIN Cancer Research Group (EA2174).
Authors: Eads Jennifer Rachel , Weitz Michelle , Gibson Michael K. , Rajdev Lakshmi , Khullar Onkar V , Lin Steven H. , Gatsonis Constantine , Wistuba Ignacio Ivan , Sanjeevaiah Aravind , Benson Al Bowen , Bahary Nathan , Spencer Kristen Renee , Saba Nabil F. , Hamilton Stanley R. , Staley Charles A. , Chakravarthy Anuradha Bapsi , Wong Terence Z. , O'Dwyer Peter J. 
Published: May 2020

TPS4651 Background: E/GEJ adenocarcinoma has a high mortality rate despite curative intent treatment. A pathologic complete response (pCR) is associated with better overall survival (OS) but occurs in less than 30% of pts. Immunotherapy is effective in the metastatic setting. Here we aim to evaluate the contribution of immunotherapy in the neoadjuvant and adjuvant settings in pts with locoregional E/GEJ cancer. Methods: This is a multi-center, randomized phase II/III trial. Surgical candidates with locoregional E/GEJ adenocarcinoma receive carboplatin AUC 2 IV and paclitaxel 50 mg/m2 IV, both weekly x 5 during concurrent radiation (50.4 Gy) either with or without nivolumab 240 mg IV during weeks 1 and 3, followed by surgery. Pts with no post-operative disease receive nivolumab 240 mg IV every 2 weeks for 12 cycles either with or without ipilimumab 1 mg/kg IV every 6 weeks for 4 cycles. Eligibility criteria include pts with T1-N1-3M0 or T2-3N0-2M0 disease whom are candidates for surgery, no prior chemotherapy or radiation for this disease, no prior immunotherapy, no significant autoimmune disease. Pts must be disease free for adjuvant treatment. Primary neoadjuvant endpoint is pCR rate; primary adjuvant endpoint is disease free survival (DFS). Secondary endpoints include toxicity, DFS and OS. Pre- and mid-treatment diffusion weighted imaging MRI will be conducted during the neoadjuvant portion of the study. A neoadjuvant safety run in of 30 pts is underway. Overall, 278 pts will be needed to detect an absolute improvement of 15% in pCR rate in pts receiving and not receiving neoadjuvant nivolumab and 236 pts will be needed to detect a HR of 0.65 in favor of adjuvant ipilimumab/nivolumab over nivolumab (90% power, one sided alpha of 0.10). Accrual is expected over 34 months at a rate of 8 patients per month. If favorable at interim analysis. Clinical trial information: NCT03604991 .
Multicenter phase II study of trastuzumab deruxtecan (DS-8201) for HER2-positive unresectable or recurrent biliary tract cancer: HERB trial.
Authors: Ohba Akihiro , Morizane Chigusa , Ueno Makoto , Kobayashi Satoshi , Kawamoto Yasuyuki , Komatsu Yoshito , Ikeda Masafumi , Sasaki Mitsuhito , Okano Naohiro , Furuse Junji , Hiraoka Nobuyoshi , Yoshida Hiroshi , Kuchiba Aya , Ogawa Gakuto , Nakamura Kenichi , Matsui Naoko , Nakamura Yoshiaki , Okamoto Wataru , Yoshino Takayuki , Okusaka Takuji 
Published: May 2020

TPS4654 Background: Biliary tract cancer (BTC) is one of the most lethal cancers with limited treatment options. Early clinical trials showed a hint of activity of HER2 blockade for HER2 positive BTC, the prevalence of which was reported to be from 5% to 20%. Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable terapeptide-based linker, and a topoisomerase I inhibitor, which showed durable response in HER2 positive breast cancer as well as in a wide spectrum of cancer subtypes in a phase I study. In addition, preclinical research demonstrated the effectiveness of trastuzumab deruxtecan for HER2 positive BTC patient derived xenograft model. This phase II study is being conducted to evaluate the efficacy and safety of trastuzumab deruxtecan for HER2 positive BTC. Methods: The main inclusion criteria are unresectable or recurrent BTC, histologically diagnosed as adenocarcinoma or adenosquamous carcinoma, confirmed HER2-expressing status by central pathological examination, refractory or intolerant to treatment including gemcitabine, and adequate organ function. Patients are registered and receive 5.4 mg/kg trastuzumab deruxtecan every 3 weeks until disease progression or unacceptable toxicities. Primary endpoint is the overall response rate (ORR) in HER2 positive (defined as IHC3+, or IHC2+/ISH+; ISH+ defined as HER2/ CEP17 ≥2.0) patients by central imaging review. The ORR in all HER2-expressing patients (including HER2 low expressing defined as IHC/ISH status of 0/+, 1+/-, 1+/+, or 2+/-), progression-free survival, overall survival, and incidence of adverse events are assessed as secondary endpoints. Thirty-two patients will be enrolled, including 24 with HER2 positive BTC as primary cohort and 8 with HER2 low expressing BTC. The study has 80% power for primary endpoint in HER2 positive BTC patients, with one-sided alpha error of 5%; threshold ORR of 15% and expected ORR of 40%. Pharmacokinetics and circulating tumor DNA analyses serially are performed. The study was initiated in May 2019 with enrollment ongoing. A total of 15 patients were enrolled as of January 2020. Funding: Japan Agency for Medical Research and Development, and Daiichi Sankyo. Clinical trial information: JMA-IIA00423 .
Phase II study of nivolumab (anti-PD1), tadalafil, and oral vancomycin in patients with refractory primary hepatocellular carcinoma or liver dominant metastatic cancer from colorectal or pancreatic cancers.
Authors: Monge B. M. Cecilia , Xie Changqing , Mabry-Hrones Donna , Wood Bradford J. , Steinberg Seth M. , Kleiner David E , Greten Tim F. 
Published: May 2020

TPS4656 Background: Treatment options for advanced hepatocellular carcinoma (HCC) and liver dominant metastatic disease from colorectal or pancreatic cancers are limited with poor overall survival. Tadalafil has shown to increase anti-tumor immunity by decreasing myeloid derived suppressor cells (MDSC) and impair tumor growth in preclinical HCC models. Oral vancomycin affects bile acid metabolizing gut commensal bacteria leading to increased CXCL16 expression in the liver resulting in NKT mediated liver-selective anti-tumor effects. This study combines immune checkpoint inhibition (ICI) treatment with nivolumab in combination with tadalafil and oral vancomycin. We aim to evaluate the synergy of the antitumor effect induced by the change in gut microbiome with oral vancomycin and the immunomodulatory effect of PDE5 inhibition combined with ICI with nivolumab in advanced liver cancer or liver metastasis. Correlative Studies: Paired liver tumor biopsies are analyzed for genomic analysis (WES, RNA-seq), immune cell infiltration, proteomics and metabolomic studies (bile acids) and chemokine expression. Stool samples are analyzed for microbiota. Blood samples are analyzed for immune monitoring, cytokine profiles and pharmacokinetics of study drugs. Serum bile acid levels are determined in blood in the 2 hour period after test meal ingestion. Methods: This is a single-arm study of nivolumab, oral vancomycin and tadalafil. Treatment is delivered in 4-week cycles (C) and continues until off treatment. Imaging is done every 8 weeks. Biopsies are done at baseline and during week 3 of C2. Nivolumab is administered on day (D)1 of each C at a dose of 480 mg IV. Tadalafil is administered orally (PO); 10 mg daily starting on D1 of C1 and continues daily until off study. Vancomycin administration starts on D1 of C1 at 125 mg PO every 6 hours for a total daily dose of 500 mg. Patients will be on vancomycin 3 weeks on, 1 week off per regimen. The study is currently enrolling without DLT. Clinical trial information: NCT03785210 .
Phase II study of pembrolizumab plus olaparib in the treatment of patients with advanced cholangiocarcinoma.
Authors: He Aiwu Ruth , Weinberg Benjamin Adam , Noel Marcus Smith , Milic Violeta P , Prins Petra , Wang Hongkun , Hartley Marion L. , Marshall John 
Published: May 2020

TPS4659 Background: Lack of an effective second-line treatment of patients (pts) with advanced cholangiocarcinoma (CC) necessitates the development of new therapies. Preclinical studies suggest CC susceptibility to PARP inhibition (PARPi): ERCC1 is underexpressed in 74% of CCs, and olaparib is selective for ERCC1 deficiency, profoundly inhibiting DNA repair. Additionally, PARPi exploits IDH mutation-related DNA damage repair deficiency, which is found in about 25% of CCs. Unfortunately, PARPi also upregulates PD-1-PD-L1 receptor-ligand binding, which attenuates anticancer immunity and counteracts the efficacy of PARPi. However, this can be prevented by PD-1 inhibition—blockade of PD-1-PD-L1 acts to re-sensitize cancer cells to T-cell killing. Hence, we hypothesize that the combination of olaparib and pembrolizumab will produce a durable anti-tumor response against CC by synergistically inducing DNA damage and increasing immune response. Methods: Thirty-six pts with advanced CC, who either failed to respond to or progressed on first-line therapy, will be enrolled to receive olaparib (300 mg PO bid) daily plus pembrolizumab (200 mg IV Q3 weeks) for 12 months, unless unacceptable toxicities or cancer progression occur, in which cases therapy will cease. MRI or CT tumor assessment will occur just before therapy, every 6 weeks for the first 6 months of therapy, and then every 9 weeks for the next 6 months of therapy (total, 12 months). Three tumor biopsies will be collected: at baseline; at week 4; and at time of progression. In each biopsy, ERCC1, PD-1, and PD-L1 expression, IDH1/2 mutation status, and immune cell (CD3 and CD8) response will be assessed. The total study duration will be 20-36 months. The primary endpoint will be overall response rate; the secondary endpoints will be PFS, OS, duration of response, and safety and tolerability. It is hypothesized that in pts with advanced CC, second-line therapy with olaparib plus pembrolizumab will improve the response rate from 17.5% to 35%, as well as increase PFS and OS compared to cytotoxic chemotherapy. Study enrollment began in Q1 2020. NCI number pending at time of abstract submission. Clinical trial information: pending at time of submission .
HGCSG 1803: Single-arm phase II study evaluating efficacy of oxaliplatin, irinotecan and S-1 combination therapy (OX-IRIS) in metastatic pancreatic cancer as first-line treatment.
Authors: Nakano Shintaro , Kawamoto Yasuyuki , Yuki Satoshi , Harada Kazuaki , Sogabe Susumu , Dazai Masayoshi , Sato Atsushi , Ishiguro Atsushi , Nakamura Michio , Kajiura Shinya , Takahashi Yasuo , Karasaki Hidenori , Tateyama Miki , Hatanaka Kazuteru , Tsuji Yasushi , Sasaki Takahide , Shindo Yoshiaki , Kobayashi Tomoe , Sakata Yuh , Komatsu Yoshito 
Published: May 2020

TPS4668 Background: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) showed improved survival compared to gemcitabine monotherapy for patients with metastatic pancreatic cancer and has become the one of the standard regimens. Despite of its clinical benefit, FOLFIRNIOX needs continuous infusion of 5-FU for 46 hours, which impairs quality of life. In other gastrointestinal cancer, infuser pomp free regimens, in which oral 5-FU drug replace the continuous infusion of 5-FU, have developed as alternative regimen. Therefore, we planned to develop new combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. We previously conducted the phase Ⅰ study for assessing the safety and determining the recommended dose of OX-IRIS regimen. Methods: To evaluate efficacy and safety of OX-IRIS, HGCSG1803 study staeted as a multicenter, non-randomized, single arm, prospective, phase II study in December 2019. The patients with untreated metastatic or relapsed pancreatic cancer are eligible for this study. OX-IRIS is administered as follows; a 30-min intravenous infusion (IV) of antiemetic, a 2-h IV of oxaliplatin at 85 mg/m2, a 1.5-h IV of irinotecan at 150 mg/m2 on day 1 and day 15 of each 4-week cycle, and S-1 (40 mg/m2) was taken orally twice daily, from after dinner on day 1 to after breakfast on day 15, followed by a 14-day rest, and to be repeated every 2 weeks until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint is response rate, and the secondary endpoints are overall survival, progression-free survival, safety, and dose intensity for each drug. A total of 40 cases are planned for registration from 18 institutions in Japan within 2.5 years. Clinical trial information: jRCTs011190008 .
Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC).
Authors: Coveler Andrew L. , Bajor David Lawrence , Masood Ashiq , Yilmaz Emrullah , Shields Anthony Frank , Javle Milind M. , Paluri Ravi Kumar , Vaccaro Gina M. , Zalupski Mark , Grilley-Olson Juneko E. , Kindler Hedy L. , Schmitt Michael W. , Gutierrez Martin 
Published: May 2020

TPS4671 Background: SEA-CD40 is an investigational non-fucosylated, humanized IgG1 monoclonal antibody directed against CD40, a co-stimulatory receptor expressed on antigen-presenting cells (APCs). Activation of CD40 on APCs upregulates cytokine production and co-stimulatory receptors, enhancing tumor antigen presentation to T cells. Preclinical data indicate that treatment of PDAC with chemotherapy in conjunction with a CD40 agonist could enhance antigen presentation and initiate an antitumor immune response (Byrne KT and Vonderheide RH, Cell Rep 2016;15, 2719–32). An ongoing Phase 1 study (SGNS40-001) is evaluating SEA-CD40 as monotherapy and in combination with pembrolizumab in patients with advanced solid or hematologic malignancies. A new cohort is enrolling to evaluate the combination of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in PDAC. Methods: The cohort consists of patients with metastatic PDAC who have had no prior therapy for metastatic disease. Patients must be ≥18 years old, with (neo)adjuvant therapy completed >4 months prior to enrollment, ECOG status ≤1, adequate renal, hepatic, and hematologic function, and measurable disease per RECIST v 1.1 criteria. A standard regimen of gemcitabine and nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle is administered with SEA-CD40 IV on Day 3. Pembrolizumab is administered every 42 days starting on Day 8. The primary objective is antitumor activity; secondary objectives are safety and tolerability and SEA-CD40 and pembrolizumab pharmacokinetics. Efficacy endpoints are confirmed RECIST ORR per investigator (primary), disease control rate (response or stable disease ≥16 weeks), duration of response, PFS, and OS. Disease is assessed every 8 weeks using RECIST and immune-based RECIST (iRECIST). Treatment continues until occurrence of unacceptable toxicity, progressive disease per iRECIST, consent withdrawal, or study closure. Assessment of dose-limiting toxicity will occur initially in groups of 6 patients to identify the recommended phase 2 dose of SEA-CD40 for the cohort. Enrollment to this cohort began in November 2019. Clinical trial information: NCT02376699 .