bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of chemotherapy and immune checkpoint blockade with pembrolizumab in the perioperative and maintenance treatment of locoregional gastric or GE junction adenocarcinoma.
Authors: Oberstein Paul Eliezer , Schrope Beth , Gonda Tamas , Sethi Amrita , Han Arnold , Schwartz Gary K. , Shah Manish A. 
Published: January 2019

TPS197 Background: Gastric cancer is a prevalent worldwide disease for which surgical resection alone is insufficient to cure the majority of localized patients. Peri-operative chemotherapy is a standard of care approach that has demonstrated modest improved survival rates. Immune checkpoint therapy has proven efficacy in a subset of patients with refractory disease but it’s role in earlier stage disease and in combination with chemotherapy is not defined. By combining chemotherapy with immune checkpoint blockade utilizing pembrolizumab we hypothesize that we will obtain improved tumor response and prolonged disease control compared to chemotherapy alone. Tissue specimens will be obtained at baseline and at the time of surgery for novel correlative studies including single cell T cell receptor characterization and expression profiling. Methods: This Phase 2, multicenter study investigates the efficacy and safety of oxaliplatin/FU based chemotherapy plus pembrolizumab in the perioperative treatment of locally advanced, resectable gastric or GE junction adenocarcinoma. A total of 40 eligible patients with T2-4 and/or N1, M0 tumors on imaging or EUS will be treated with capecitabine, oxaliplatin and epirubicin (epirubicin can be omitted at investigator discretion) plus fixed dose pembrolizumab at 200mg for 3 cycles prior to surgery plus one additional dose of pembrolizumab alone before surgery. Following completion of post-operative chemotherapy with pembrolizumab, patients continue pembrolizumab for 1 year of maintenance therapy (17 cycles). The primary endpoint is disease free survival at 24 months (DFS 24) with an estimated 80% power to detect a clinically significant 24 month DFS rate of 65%. A key secondary endpoint is pathCR at surgery, additional endpoints include response rate (RECIST 1.1), 12 month DFS, and overall survival. Safety, including surgical outcomes, will be assessed. Multiple correlative analyses utilizing baseline and post-treatment tissue, PD-L1 staining, and serum samples will also be performed. Enrollment opened in March 2017. Clinical trial information: NCT02918162.
A phase I/II multi-center study of nivolumab and carboplatin/paclitaxel with radiation therapy (RT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Giuroiu Iulia , Ku Geoffrey Yuyat , Leichman Lawrence P. , Du Kevin Lee , Oh Philmo , Levinson Benjamin A. , Iqbal Syma , Thomas Charles R. , Wu Jennifer J. 
Published: January 2019

TPS199 Background: ESCC comprises 80% of esophageal cancers worldwide. Preoperative chemoRT is a standard-of-care based on the CROSS trial ( N Engl J Med 2012;366:2074-2084), which reported encouraging pathologic complete response (pCR) and overall survival (OS). Surgery is often deferred in patients with clinical CR (cCR) based on lack of overall survival (OS) benefit ( J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC ( Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. ESCC has a high somatic mutation rate and treatment with chemoRT may augment the abscopal effect. Methods: Our trial aims to establish the safety and tolerability (phase I), as well as the efficacy (phase II) of nivolumab added to a standard chemoRT backbone for patients with TanyN1-3 or T3-4N0M0 ESCC. Phase I will enroll up to 12 patients and phase II, up to 44, per an optimal two-stage design. The phase I primary endpoint is unacceptable toxicity at 28 days after the last dose of chemotherapy. Phase II primary endpoints are cCR (endoscopy + PET/CT), pCR for patients undergoing surgery, and median progression-free survival and OS, which will be estimated via Kaplan Meier curves. Extensive tumor and blood immune correlative studies are planned. Clinical trial information: NCT03278626. [Table: see text]
A phase 1b (open-label)/phase 2 (randomized, double-blinded) study evaluating nab-paclitaxel and gemcitabine with or without olaratumab in first-line treatment of metastatic pancreatic cancer.
Authors: Bendell Johanna C. , Pelzer Uwe , Womack Mark S. , Borazanci Erkut Hasan , Bahary Nathan , Garrido-Laguna Ignacio , Maur Michela , Prater Tyler , Levy Donna Elise , Cronier Damien , Ramage Sam , Macarulla Teresa 
Published: January 2019

TPS524 Background: Olaratumab is a human IgG1 monoclonal antibody that specifically binds human platelet-derived growth factor receptor (PDGFR)-α and blocks PDGF-mediated signaling pathways. Increased PDGFRα expression is observed in pancreatic cancer tissue, and has been suggested to play a role in the mesenchymal transition of pancreatic cancer. An ongoing trial designed to evaluate the safety and efficacy of olaratumab in combination with nab-paclitaxel/gemcitabine (nPG) in patients with unresectable metastatic pancreatic cancer not previously treated for metastatic disease is currently being conducted. Methods: JGDP (NCT03086369) is a global Phase 1b/Phase 2 study being conducted to evaluate the safety and efficacy of olaratumab in combination with nPG as first-line therapy in patients with Stage IV pancreatic cancer (ECOG PS ≤1). In the Phase 1b portion of the study, patients will receive intravenous (iv) olaratumab following a 3+3 dose escalation scheme at two different schedules: on Days 1, 8 and 15 at doses of 15 mg/kg and 20 mg/kg, or on Days 1 and 15 at 20 mg/kg and 25 mg/kg. Olaratumab will be given in combination with nPG (125 mg/m2 iv/1000 mg/m2 iv) on Days 1, 8, and 15 of a 28-day cycle. After the maximum tolerated dose has been identified, additional patients will be enrolled in a cohort expansion to confirm the safety of the combination prior to proceeding to the Phase 2 portion of the study. In the Phase 2 study, approximately 162 patients will be randomized at a 1:1 ratio to receive olaratumab at the recommended Phase 2 dose regimen or placebo, both in combination with nPG (125 mg/m2 iv/1000 mg/m2 iv). Treatment will continue until disease progression or other discontinuation criteria are met. The primary end point of the Phase 2 study is overall survival; a 2-sided α level of 0.20 will be applied. Assuming OS HR = 0.67, there is ≥80% power to show a significant difference in OS between study arms. Secondary end points include progression free survival, duration of response, objective response rate, patient-reported outcomes, and safety. As of September 2017, enrollment for the Phase 1b study is currently ongoing. Clinical trial information: NCT03086369.
A single arm phase II study of rucaparib maintenance in patients with advanced pancreatic adenocarcinoma and a known deleterious BRCA1, BRCA2 or PALB2 mutation who have achieved stability on platinum therapy.
Authors: Reiss Kim Anna , Maxwell Kara Noelle , Nathanson Katharine , Teitelbaum Ursina R. , O'Hara Mark H. , O'Dwyer Peter J. , Schneider Charles , Carpenter Erica L. , Mick Rosemarie , Domchek Susan M. 
Published: January 2019

TPS531 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a median overall survival of < 1 year. A subset of PDAC is characterized by a homologous recombination deficiency (HRD). The most well-defined patients within this group are those with deleterious mutations in BRCA1, BRCA2 and PALB2. This subset of tumors respond exceptionally well to treatment with platinum agents, leading to durable responses. However, cumulative toxicity can complicate or even prevent continued therapy, and there is an unmet need to establish maintenance strategies for such patients.Prior studies have shown that BRCA1 and BRCA2 associated PDACs respond to PARP inhibitors. Cross-resistance to platinum and PARP inhibitors exists, so initiating PARP inhibitor therapy after the development of platinum-resistance is an inferior approach. In this setting, we have designed a phase II trial of rucaparib as maintenance therapy for patients with deleterious BRCA1, BRCA2 or PALB2 who have sustained stability on platinum-based treatment. Methods: We have enrolled 2 of 42 planned patients on study NCT03140670. Eligibility criteria include inoperable PDAC, a known somatic or germline deleterious mutation in BRCA1, BRCA2 or PALB2 and stability on platinum-based chemotherapy for ≥16 weeks. Patients who have progressed on platinum-based treatment or who have received prior therapy with PARP inhibitors are excluded. Patients will receive oral rucaparib twice daily continuously in 28-day cycles. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include response rate, duration of response and overall survival. A pre-treatment tumor biopsy and biopsy at progression will be obtained, as well as serial blood collections for circulating tumor material. Correlative assays will include tumor and circulating tumor DNA sequencing to identify genomic predictors of outcome and study resistance mechanisms. Clinical trial information: NCT03140670.
A study of ramucirumab (LY3009806) versus placebo in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein (REACH-2).
Authors: Zhu Andrew X. , Galle Peter R. , Kudo Masatoshi , Finn Richard S. , Qin Shukui , Xu Yihuan , Abada Paolo , Llovet Josep 
Published: January 2019

TPS538 Background: Ramucirumab (RAM), a human IgG1 mAb, inhibits ligand activation of VEGFR2. In REACH, while improvement in overall survival (OS) in the overall population was not statistically significant, meaningful improvement was observed in a patient subgroup with baseline alpha-fetoprotein (AFP) ≥400 ng/mL (N = 250) (HR = 0.67, p = 0.006; median OS [months] RAM 7.8 vs placebo [pbo] 4.2). RAM treatment was generally well tolerated in patients with advanced hepatocellular carcinoma (HCC) after prior sorafenib (SOR). Methods: REACH-2 is a randomized, double-blind, pbo-controlled, global phase 3 study of RAM+best supportive care (BSC) vs pbo+BSC in patients with HCC and elevated baseline AFP following therapy with SOR. Eligibility includes Child-Pugh < 7; Barcelona Clinic Liver Cancer Stage C or B disease not amenable/refractory to locoregional therapy; AFP ≥400 ng/mL; ECOG PS 0 or 1; ≥1 measurable lesion; and disease progression during/after SOR, or SOR intolerance. Patients with history of hepatic encephalopathy, clinically meaningful ascites, liver transplant, or hepatic locoregional therapy after SOR are not eligible. Eligible patients will be randomized 2:1 to 8 mg/kg RAM or pbo (14-day cycle) and treated until radiographic/clinical disease progression or discontinuation criteria are met. The primary objective is OS; secondary objectives include progression-free survival (PFS), objective response rate, safety, and patient-focused outcomes. Recognizing expanding treatment options for HCC, a second, single arm, open-label cohort of ~44 patients will be enrolled with the same eligibility and treatment as the main cohort except a requirement for prior treatment other than SOR (eg, mTKIs, immune checkpoint inhibitors) and some exclusions of checkpoint inhibitor-related adverse events. The primary objective is safety; secondary objectives include OS, PFS, and patient-focused outcomes. Additionally, a third randomized cohort of ~65 Chinese patients will be enrolled with the same objectives, eligibility, treatment, and evaluations as the main cohort. Analysis of Open-Label and Chinese cohorts will be independent of the main REACH-2 cohort. Clinical trial information: NCT02435433.
Randomized phase III study of observation versus adjuvant capecitabine and oxaliplatin in curatively resected small bowel adenocarcinoma: A Japan Clinical Oncology Group study (JCOG1502C).
Authors: Honma Yoshitaka , Ueno Makoto , Kanemitsu Yukihide , Ohkawa Shinichi , Kitahara Hideaki , Mizusawa Junki , Katayama Hiroshi , Nakamura Kenichi , Furuse Junji , Shimada Yasuhiro 
Published: January 2019

TPS539 Background: Small bowel adenocarcinoma (SBA) is extremely rare tumor. Surgery is broadly applied as a standard treatment for localized SBA. However, the patients with localized SBA have poor prognosis even after curative resection (5-year survival: 40-65%), and most of them experience relapse. To prevent relapse, postoperative therapies are considered as most promising. However, there is no prospective study of postoperative therapies for curatively resected SBA patients and which regimens improve prognoses is unknown. For metastatic SBA, fluoropyrimidine and oxaliplatin is now regarded as global standard chemotherapy. Therefore, Japan Clinical Oncology Group (JCOG) planned a multicenter randomized phase III trial to confirm the superiority of postoperative capecitabine and oxaliplatin (CAPOX) to observation for curatively resected SBA under the Advanced Medical Care System of the Ministry of Health, Labour and Welfare, Japan. This study is a counterpart trial of BALLAD trial conducted in International Rare Cancer Initiative (IRCI) (clinical trials gov; NCT02502370), and the integrated analysis of BALLAD trial and JCOG1502C is planned. Methods: Eligibility criteria include histologically proven adenocarcinoma located in the duodenum (except Ampulla of Vater) / jejunum / ileum, curatively resected with regional lymph nodes dissection, pathological stage I (T1b-2N0M0) / stage II / stage III. Eligible patients are randomized into observation arm or CAPOX arm. CAPOX (130 mg/m2 of oxaliplatin on day 1, and 1000 mg/m2 of capecitabine twice a day for 14 days) is repeated every 3 weeks for 6 months (total 8 courses). The primary endpoint is RFS. The 3-year RFS of observation arm is assumed to be 70% and expected a 10% increase in CAPOX arm. The sample size was calculated as 150 (75 per arm) with a one-sided alpha level of 10%, a statistical power of 70%, an accrual period of 6.5 years. This study has been registered in the UMIN Clinical Trials Registry (UMIN000027280). This trial was activated in 9 May 2017, and no patients was enrolled as of Sep 2017. We will increase the number of participating sites up to 20 throughout Japan. Clinical trial information: UMIN000027280.
A phase I/II trial of NBTXR3 nanoparticles activated by SBRT in the treatment of liver cancers.
Authors: Chajon Enrique , Pracht Marc , De Baere Thierry , Nguyen France , Bronowicki Jean-Pierre , Vendrely Veronique , Baumann Anne-Sophie , Croisé-Laurent Valérie , Deutsch Eric 
Published: January 2019

TPS551 Background: A new class of material with high electron density, hafnium oxide, was designed at the nanoscale (NBTXR3) to efficiently enhance the energy dose deposit from within the tumor cells and increase lethality of tumors, when exposed to radiotherapy (RT). The physical mode of action of NBTXR3 may represent a breakthrough approach for the local treatment of liver cancers, as it does not engage liver and renal functions, i.e. nanoparticles are not metabolized and not excreted by kidney. A phase I/II trial has been implemented for the treatment of hepatocellular carcinoma and liver metastasis [NCT02721056]. The study is currently recruiting patients. Methods: Patients (pts) receive a single intralesional (IL) injection of NBTXR3 (53.3g/L) at Volume levels equivalent to 10%, 15%, 22% and 33% of the baseline tumor volume, followed by RT (SBRT, 45Gy / 3 fractions / 5 to 7 days). For the Phase I part, primary endpoints include determination of the Recommended Dose and Dose Limiting Toxicities (DLT). The Phase II part will test three different groups of patients, HCC with portal vein thrombus, HCC without portal vein thrombus and a third cohort with liver metastases. Primary endpoints are complete response rate and safety. Results: Enrollment was completed for Volume levels 10% (6 pts) and 15% (4 pts) and is currently recruiting patients at 22% level. The NBTXR3 injections were successful in all cases. Radiotherapy has been delivered as planned without any DLT occurrence. No serious adverse event (SAE) related to NBTXR3 or the treatment procedure occurred. Three adverse events related to the injection were reported and no adverse event related to NBTXR3. Importantly, NBTXR3 nanoparticles did not have any impact on the reliability of image-guided radiation therapy (IGRT). Conclusion: The injection of NBTXR3 was safe and well tolerated at these levels. Patients received the planned RT. No DLT occurred. Enrollment is now opened at the 22% level. NBTXR3 shows promising results in terms of safety and antitumor activity and is also currently evaluated in other six clinical studies. Clinical trial information: NCT02721056.
A prospective biomarker trial of microbiome, immune, and genomic markers as predictors of radiation response in anal squamous cell carcinoma.
Authors: Colbert Lauren Elizabeth , Lin Daniel , Minsky Bruce D. , Holliday Emma Brey , Klopp Ann , Das Prajnan , Eng Cathy , Morris Van Karlyle , Taniguchi Cullen M. 
Published: January 2019

TPS869 Background: Preclinical evidence suggests that the microbiome plays a significant role in carcinogenesis and in response to immunotherapy and chemotherapy, but little is known about the role of the microbiome in response to radiation. Our group previously demonstrated that in patients with cervical squamous cell carcinoma (SCC), radiation response and immune response to radiation are improved with increased rectal microbial diversity. Methods: We are currently enrolling patients with local anal SCC undergoing definitive chemoradiation on a prospective biomarker trial evaluating changes in the gastrointestinal microbiome, immune microenvironment, and whole genome sequencing using a novel, non-invasive swab biopsy technique in addition to serial blood collections. This biopsy technique allows novel evaluation of dynamic changes throughout the course of chemoradiation. Microbiome sequencing is performed using 16s rRNA sequencing. Immune profiling is done using multiparametric flow cytometry for T-cell activation and exhaustion phenotypes and T-cell receptor sequencing. Inclusion criteria are biopsy proven HPV-related SCC of the anus, with no evidence of metastatic disease, and undergoing definitive chemoradiation. Our population is uniquely treated with cisplatin/5-FU based chemotherapy, rather than lymphotoxic mitomycin-C, allowing unique evaluation of immune populations. The primary endpoint of this study is complete tumor response based on pelvic MRI and digital rectal exam at three weeks. Secondary endpoints include FDG-avid diseases at 3 months and disease recurrence. To date we have accrued 10 patients out a planned 30 patient pilot cohort. We expect the remainder of these patients to be accrued by December 2017.
Phase 1b/2 study of binimetinib (BINI) in combination with nivolumab (NIVO) or NIVO plus ipilimumab (IPI) in patients (pts) with previously treated microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) with RAS mutation.
Authors: Bendell Johanna C. , Kopetz Scott , Middleton Mark R. , Eves P. Taylor , Bozon Viviana , Boyd Adam P. , Schellens Jan H.M. 
Published: January 2019

TPS870 Background: Approximately 96% of CRCs have an MSS phenotype, which results in more immunologically quiescent tumors for which immunotherapies are largely ineffective (Lee et al. 2015; Overman et al. 2016). Pts with MSS CRC and activating RAS mutation (35%–45% of CRCs) have treatment options limited still further because anti-EGFR monoclonal antibodies (eg, cetuximab) are ineffective owing to dominant activation of RAS in the MAPK pathway (Douillard et al. 2014). However, preclinical and preliminary clinical data suggest that MAPK pathway inhibition enhances antigen presentation and T-cell cytotoxicity to positively modulate the efficacy of checkpoint inhibitors (Brea et al. 2016; Bendell et al. 2014). The main objective of this open-label multicenter phase 1b/2 study is to evaluate whether the potential positive modulation of NIVO or NIVO plus IPI, when combined with BINI, translates into clinically meaningful overall response in pts with MSS mCRC and RAS mutation. Methods: The study will enroll ~90 previously treated pts (1 or 2 prior regimens), ~42 in phase 1b and ~48 in phase 2. The primary objective of phase 1b will be to determine the recommended phase 2 dose (RP2D) of BINI in combination with NIVO ± IPI. Dose finding in the doublet arm will begin with BINI 45 mg BID + NIVO 480 mg Q4W; the triplet arm will begin with the BINI RP2D from the doublet arm + NIVO 480 mg Q4W + IPI 1 mg/kg Q8W. In phase 2, pts will be randomized 1:1 to doublet or triplet arms, incorporating the BINI RP2Ds found in phase 1b; treatment will continue in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, loss to follow-up, or death. The primary objective for phase 2 will be to assess response by RECIST version 1.1. The study will also characterize safety and PK. CT.gov Identifier: Clinical trial information: NCT03271047.
A randomized phase III clinical trial of sequential capecitabine or 5-FU plus bevacizumab (Cape/5-FU+Bmab) followed by Cape/5-FU plus oxaliplatin plus Bmab (CapeOX/mFOLFOX6+Bmab) versus combination CapeOX/mFOLFOX6+Bmab in advanced colorectal cancer: The C-cubed (C3) study.
Authors: Ojima Hitoshi , Mishima Hideyuki , Sawaki Akira , Nagasaka Takeshi , Shimokawa Mototsugu , Inukai Michio , Shinozaki Katsunori , Tanioka Hiroaki , Nasu Junichiro , Nishina Tomohiro , Hazama Shoichi , Okajima Masazumi , Tsuji Akihito , Tsuji Yasushi , Munemoto Yoshinori , Yamaguchi Shigeki , Yamaguchi Yoshiyuki 
Published: January 2019

TPS872 Background: Less intensive regimens, focusing on survival and disease control, may be better first-line treatments in unresectable metastatic colorectal cancer (mCRC). Several randomized trials suggested that sequential cytotoxic agents in mCRC may improve overall survival compared with combination chemotherapy. This study investigated whether sequential treatment with Bmab-based first-line therapy with oxaliplatin has superior efficacy to combination treatment for unresectable mCRC. Methods: This study is a two-arm, multicenter, open-label, randomized phase III trial in Japan, comparing the efficacy and safety of sequential Cape/5-FU+Bmab with escalation to CapeOX/mFOLFOX6+Bmab versus combination CapeOX/mFOLFOX6+Bmab as the first-line treatment of mCRC. The primary endpoint is Time to failure of strategy (TFS). In the sequential arm (Arm A: oxaliplatin ‘wait-and-go’), treatment escalation from Cape/5-FU+Bmab to CapeOX/mFOLFOX6+Bmab is recommended for progressive disease. In the combination arm (Arm B: oxaliplatin ‘stop-and-go’), de-escalation from CapeOX/mFOLFOX6+Bmab to Cape/5-FU+Bmab is possible after 12 weeks of treatment. Re-escalation to CapeOX/mFOLFOX6+Bmab after progressive disease is considered only for patients who received de-escalation of oxaliplatin, not caused by oxaliplatin-associated toxicity, after 12 weeks of treatment. A target sample size of 304 evaluable patients is considered sufficient to detect a hazard ratio of 0.69 for the TFS of the sequential ‘wait-and-go’ approach compared with the combination ‘stop-and go’ approach with 80% power and a 2-sided significance level of 5%. From December 2014 to September 2016, 311 patients were enrolled across 81 centers in Japan. The follow-up period is until March 2018, and results are expected in 2019, and results are expected in 2019. Clinical trial information: 000015405.