bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 trial of durvalumab and radiation revaccination in patients with metastatic adenocarcinoma of the pancreas who have progressed through first-line chemotherapy.
Authors: Chuong Michael David , Badiyan Shahed Nicolas , Mehta Minesh P. 
Published: January 2019

TPS461 Background: Emerging data suggest that immunotherapy combined with radiation therapy (RT) can lead to robust anti-tumor immune responses within many tumor types. While not highly immunogenic, pancreatic cancer has been shown to respond to immunotherapy especially when combined with RT. Our research hypothesis is that the combination of RT and immunotherapy (durvalumab) is well tolerated and stimulates a clinically significant pancreas-cancer specific immune response. Methods: Metastatic pancreatic cancer patients who have progressed through first-line chemotherapy will receive durvalumab every 4 weeks and will concurrently receive 24 Gy in 3 daily fractions to one pancreatic cancer lesion during week 3 followed by 24 Gy in 3 daily fractions to a second lesion during week 5. Durvalumab will continue until disease progression or unacceptable toxicity. Two lesions (instead of only one) will receive RT sequentially because of the potential for radiation “revaccination” to generate a more robust anti-tumor immune response, as our group previously published from a pancreas cancer mouse model. The primary objective is to evaluate whether the combination of RT and durvalumab can improve median PFS compared to chemotherapy historical control data. Secondary endpoints include evaluation of toxicity, overall survival, overall response rate, clinical benefit rate, and time to in-field progression. We will evaluate whether there is any correlation between durvalumab plus RT and levels of CD8 T cells, regulatory T cells, or myeloid derived suppressor cells in the peripheral blood at various intervals before, during, and after therapy. We will use a 1-sided test with a 5% significance level (a) to test the uni-directional hypothesis that the median PFS is prolonged from 3 to 4.5 months by combining RT with durvalumab. With a statistical power (1-b) of the study of 80%, we estimate an accrual time of 26 months for a total sample size of 39 patients. A positive signal from this trial that RT revaccination with concurrent checkpoint inhibitor is effective and well tolerated would provide support for a randomized trial. Clinical trial information: NCT03490760.
PANOVA-3: A phase III study of tumor treating fields with nabpaclitaxel and gemcitabine for front-line treatment of locally advanced pancreatic adenocarcinoma (LAPC).
Authors: Weinberg Uri , Giladi Moshe , Bomzon Zeev , Kirson Eilon David 
Published: January 2019

TPS469 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of patients with glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. The Phase 2 PANOVA study was the first trial testing TTFields in pancreatic cancer patients, and demonstrated the safety of TTFields when combined with nab-paclitaxel and gemcitabine in both metastatic and LAPC. The Phase 3 PANOVA-3 trial (NCT03377491) is designed to test the efficacy of adding TTFields to nab-paclitaxel and gemcitabine combination in LAPC. Methods: Patients (N = 556) with unresectable, LAPC (per NCCN guidelines) will be enrolled in this prospective, randomized trial. Patients should have an ECOG score of 0-2 and no prior progression or treatment. Patients will be stratified based on their performance status and geographical region, and will be randomized 1:1 to TTFields plus nab-paclitaxel and gemcitabine or to nab-paclitaxel and gemcitabine alone. Chemotherapy will be administered at standard dose of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2 once weekly). TTFields (150kHz) will be deilvered at least 18 hours/day until local disease progression per RECIST Criteria V1.1. Follow up will be performed q8w, including a CT scan of the chest and abdomen. Following local disease progression, patients will be followed monthly for survival. Overall survival will be the primary endpoint and progression-free survival, objective response rate, rate of resectability, quality of life and toxicity will all be secondary endpoints. Sample size was calculated using a log-rank test comparing time to event in patients treated with TTFields plus chemotherapy with control patients on chemotherapy alone. PANOVA-3 is designed to detect a hazard ratio 0.75 in overall survival. Type I error is set to 0.05 (two-sided) and power to 80%. Clinical trial information: NCT03377491.
Phase II HEPANOVA trial of tumor treating fields concomitant with sorafenib for advanced hepatocellular carcinoma.
Authors: Grosu Anca , Gkika Eleni , Brunner Thomas B. , Thimme Robert , Weinberg Uri 
Published: January 2019

TPS470 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of hepatocellular carcinoma (HCC), leading to a significant increase in cell death. The Phase 2 HEPANOVA study is the first trial testing TTFields in HCC patients, and is designed to test the safety and efficacy of adding TTFields to sorafenib in advanced HCC. Methods: Patients (N = 25) with unresectable HCC who are not amenable to any local treatment will be enrolled in this prospective, single-arm study. The study enrolls patients with ECOG score of 0-2 and Barcelona clinic liver cancer (BCLC) stage 0-C. Patients must have a measurable disease per RECIST Criteria. Having implanted electronic devices in the torso is exclusionary. Sorafenib will be administered at standard dose (400 mg twice daily). TTFields (150 kHz) will be delivered for 18 hours/day until local disease progression per RECIST Criteria. Clinical follow up will be performed q4w, and a CT/MRI scan q12w. Following disease progression in the liver, patients will discontinue TTFields and be followed monthly for survival. Overall response rate will be the primary endpoint and in-field control rate, progression-free survival rate at 12 month (PFS12), OS rate at 1 year and toxicity will all be secondary endpoints. Sample size was calculated using an Exact test for proportions considering the weighted average of ORR of patients who had either complete or partial response per RECIST criteria in historical studies with sorafenib is 4.5%. A sample size of 25 patients was required to achieve a power of approximately 80% at a one-sided alpha level of 0.05 using a single sample Exact test for proportions. Clinical trial information: NCT03606590.
NSABP FC-11: A phase II study of neratinib (N) plus trastuzumab (T) or n plus cetuximab (C) in patients (pts) with "quadruple wild-type (WT)" (KRAS/NRAS/BRAF/PIK3CA WT) metastatic colorectal cancer (mCRC) based on HER2 status—Amplified (amp), non-amplified (non-amp), WT, or mutated (mt).
Authors: Jacobs Samuel A. , Lee James J. , George Thomas J. , Yothers Greg , Kolevska Tatjana , Yost Kathleen J , Wade James Lloyd , Buchschacher Gary L , Stella Philip J. , Shipstone Asheesh , Pogue-Geile Katherine L. , Srinivasan Ashok , Lucas Peter C. , Allegra Carmen Joseph 
Published: January 2019

TPS716 Background: HER2 has been shown to be a validated therapeutic target for the treatment of mCRC. Preclinical and clinical evidence supports the use of HER2-targeted agents in each of these mCRC cohorts. In HERACLES, treatment–refractory, KRAS exon 2 (codons 12 and 13) WT, HER2 amp mCRC pts were treated with T and lapatinib (L). Objective response rate (CR or PR) was 8/27 and disease control rate (CR, PR, and SD > 16 wks) was 16/27. Duration of response ranged from 24-94+ wks. Anecdotal reports have shown activity of N in HER2 mts from several cancer types. In mCRC PDX models with qualifying HER2 mts, T plus N is more active than either drug alone. In quad WT, HER2 non-amp PDX models, C plus TKI resulted in major tumor regressions not seen with C monotherapy. In NSABP FC-7, a trial of C + N in cetuximab refractory pts, HER2 amp was observed in 2/23 primary tissue samples; after C exposure, HER2 amp was seen in 5/17 samples, presumably signal upregulation under selective pressure of C. HER2 amp was concordant in tissue (CISH) and blood using cfDNA. Methods: This multi-center 3-cohort phase II trial is currently enrolling pts (total planned N = 35). Pts with quad WT, HER2 amp (n = 15) with prior anti-EGFR therapy and/or HER2 mt mCRC (n = 5) will receive T 4 mg/kg iv loading dose followed by 2 mg/kg/wk and N 240 mg po daily (Arm 1). Pts with quad WT, HER2 non-amp (n = 15) with no prior anti-EGFR therapy will receive C 400 mg/m2 iv loading dose followed by 250 mg/m2/wk, and N 240 mg (Arm 2). Specific pt eligibility for quad WT and HER2 status are defined below: Arm 1: HER2 amp confirmed in blood by Guardant360 assay, and prior treatment with C or panitumumab (P). HER2 mt (with qualifying mt) with or without prior treatment with C or P. Arm 2: HER2 non-amp or HER2 amp and no prior therapy with C or P. The primary aim is 6-mos progression-free survival for each cohort. Secondary aims: response rates and toxicity. Exploratory aims: genetic and molecular analyses. Specific drug combinations will be evaluated in PDX models. NCT03457896. Support: Puma Biotechnology, Inc.; NSABP Foundation, Inc. Clinical trial information: NCT03457896.
Nintedanib in metastatic appendiceal carcinoma.
Authors: Kc Birendra , Ahmad Mufti Naeem , Kadakia Kunal C. , Nazemzadeh Reza , Salem Mohamed E. , Chai Seungjean , Salmon John Stuart , Symanowski James Thomas , Boselli Danielle , Hwang Jimmy J. 
Published: January 2019

TPS723 Background: Appendiceal carcinomas are rare with an incidence of about 0.12 cases per 1,000,000 people per year. There is limited, mostly retrospective data in the treatment of metastatic appendiceal carcinomas. Generally, fluoropyrimidine-based therapy is used in the first line, adapting regimens for metastatic colorectal cancer. However, beyond progression, no treatments have shown clear activity. In appendiceal cancer, high vascular endothelial growth factor receptor (VEGFR)2 expression has been correlated with poor survival. Moreover, malignant ascites has been demonstrated to have elevated levels of VEGF. Nintedanib is an oral tyrosine kinase inhibitor of VEGFR which demonstrated activity in lung and ovarian cancer in clinical trials, and has undergone investigation in heavily pretreated metastatic colorectal cancer. Given the analogies between appendiceal and colorectal cancer and potentially ovarian cancer, and the limited information about the optimal treatment of metastatic appendiceal carcinomas, further investigation with nintedanib is warranted. Methods: This is a single arm, open label, investigator initiated, two-stage phase II trial (NCT 03287947) in metastatic appendiceal cancer patients after failure (defined as progression on or within 6 months or intolerance) of initial fluoropyrimidine-based therapy and at least one measurable site of disease. The trial started enrolling patients in June 2018, and up to 39 subjects will be enrolled. They will be treated with 200 mg of oral nintedanib twice daily and undergo disease evaluation every two months. The primary objective of this study is to evaluate the disease control rate (DCR), the composite of objective response and stable disease per RECIST 1.1. Secondary objectives include evaluation of safety and toxicity, objective response rate (ORR), 6-month progression free survival (PFS) and overall survival (OS). DCR, ORR & 6-month PFS will be estimated with the corresponding 95% Clopper-Pearson confidence interval. PFS & OS will be estimated using Kaplan-Meier techniques. Exploratory objectives include evaluation of serum VEGF, ascites VEGF, hypertension and paracentesis frequency in subjects with ascites at study entry. Clinical trial information: NCT 03287947.
Phase Ib study of talimogene laherparepvec (T-VEC) injection into liver metastases (LMs) in combination with intravenous (IV) atezolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or colorectal cancer (CRC).
Authors: Hecht J. Randolph , Chan Arlene , Martin Miguel , Mach Nicolas , Hurvitz Sara A. , Rottey Sylvie , Pelzer Uwe , Liu Chunxu , Chan Emily 
Published: January 2019

TPS725 Background: T-VEC is a genetically modified, oncolytic herpes simplex virus type 1 designed to selectively replicate within tumors and produce GM-CSF to enhance systemic antitumor immune responses. Atezolizumab is a monoclonal antibody checkpoint inhibitor (CPI) that targets PD-L1. The safety of intrahepatic administration of T-VEC has been demonstrated in a prior clinical trial (NCT02509507). A previous trial of T-VEC in combination with a CPI in advanced melanoma demonstrated improved responses compared to those with a CPI alone (Puzanov et al. JCO. 2016; 34:2619-26). We hypothesize that T-VEC combined with a CPI may also be effective in other tumor types. This phase 1b, multicenter study evaluates the safety of intrahepatic injection of T-VEC in combination with IV atezolizumab in pts with TNBC or CRC with LMs. Methods: The study will enroll up to 36 pts in two parallel cohorts (18 TNBC, 18 CRC) at sites in the USA, Europe, and Australia. The primary objective is to evaluate the incidence of dose-limiting toxicities (DLTs). Secondary objectives include objective response rate, lesion-level responses in injected and uninjected tumors, progression-free survival, and overall survival. Key eligibility criteria include age ≥ 18 years, confirmed diagnosis of TNBC or CRC with LMs, ECOG performance status 0/1, adequate organ function, disease progression during or after ≥ 1 prior standard-of-care systemic therapy for metastatic disease, and ≥ 1 measurable, injectable LM. T-VEC will be given by image-guided intralesional injection of up to 4 mL of 106 plaque forming units (PFU)/mL on day 1 and up to 4 mL of 108 PFU/mL every 21 days thereafter; atezolizumab 1,200 mg IV will be given on day 1 and every 21 days thereafter. The DLT-evaluation period is the first two cycles (1 cycle = 21 days). Interim safety analysis will occur after the first 4–6 pts have become DLT evaluable. Up to six cycles of T-VEC will be given with an additional 6 cycles allowed. After cycle three, nonhepatic lesions may be injected, subject to protocol-defined criteria. The study opened for enrollment in January 2018. (NCT03256344) Clinical trial information: NCT03256344.
Evaluation of health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC): A prospective, multicenter, open-label, double-arm trial of trifluridine/tipiracil (FTD/TPI) versus best supportive care (BSC).
Authors: Karthaus Meinolf , Welslau Manfred , Riera-Knorrenschild Jorge , Kretzschmar Albrecht , Vehling-Kaiser Ursula , Mahlberg Rolf , Pelz Henning , Lindig Udo , Fischer von Weikersthal Ludwig , Heinemann Volker ,   TALLISUR Study Group
Published: January 2019

TPS726 Background: The RECOURSE trial in pts with refractory mCRC showed improvement in OS (7.1 vs 5.3 mo, p < 0.001), but had no formal assessment of QoL. Thus, the TALLISUR trial is designed to investigate the HRQoL in pts treated with FTD/TPI and those who are treated with BSC alone on patient´s request while being suitable for treatment (Tx) with FTD/TPI prospectively. This novel design of a double-arm trial with BSC as appropriate comparative Tx is addressing assessment requirements (i.e. data on survival, morbidity and QoL) for the German Federal Joint Committee (GBA). Methods: Pts who have been previously treated with, or are not candidates for available Ctx including 5-FU, oxaliplatin, irinotecan, anti-VEGF-, and anti EGFR-agents with adequate organ functions independent from their ECOG status. Tx is FTD/TPI 35 mg/m2 d 1-5 and 8-12 qw d 28 or BSC. Efficacy is documented by PFS (clinical or radiological), OS and an exploratory analysis of RR while safety includes type, incidence and severity of FTD/TPI-related AEs. QoL will be assessed by means of the EORTC QLQ-C30 and EQ-5D-5L questionnaires for one year, close safety observation and/or FU phase. The primary endpoint (EP) is the rate of responders with unchanged or improved HRQoL. Major exclusion criteria include other tumor therapy as Rtx, and intestinal obstruction. Response will be defined as an improvement or stabilization compared to the baseline score of the global health status/QoL scale. Response is calculated as mean of the score of the EORTC QLQ-C30, global health status/QoL scale at all scheduled time points of QoL analysis in the time interval from d -2 before start of Cycle 2 until the end of Tx/close observation compared to the baseline score of the global health status /QoL scale. A RR of 45%±10% is assessed as appropriate in pts with ≥2 cycles FTD/TPI. A total of 195 pts are needed to answer the question with a 2-sided type I error of 5%. The strategy will be regarded successful if the lower boundary of the CI for the RR is ≥35%. TALLISUR started 09/2017 (EudraCT-No 2017-000292-83) and has recruited 160 mCRC pts in total (17th Sep 2018). Clinical trial information: 2017-000292-83.
PD-1 antibody combined with COX inhibitor in MSI-h/dMMR or high TMB colorectal cancer: A single arm phase II study.
Authors: Wu Zehua , Deng Yanhong , Zhang Jianwei , Hu Huabin , Cai Yue , Ling Jiayu , Deng Ru 
Published: January 2019

TPS729 Background: Programmed death protein 1 (PD-1) antibody has been to approved in patients with MSI-H/dMMR colorectal cancer and has achieved significant efficacy. It's also reported that tumor mutation burden (TMB) may be another biomarker of response to PD-1 therapy. But there were about 50-60% of patients with MSI-H/dMMR were insensitive to PD-1 antibody. Cyclooxygenase (COX) inhibitor has been proved to prevent adenomas in colorectal and it is safe for most of the patients. Preclinical data demonstrate that inhibition of COX synergizes with anti-PD-1 blockade in inducing eradication of tumors. Methods: This single arm, phase II trial will assess the efficacy and safety of combination of PD-1 antibody and COX inhibitor in patients with MSI-H/dMMR or high tumor mutation burden colorectal cancer. Patients diagnosed with MSI-H/dMMR or high tumor mutation burden colorectal cancer which was unresectable and had at least one lines of chemotherapy fail or refuse to receive chemotherapy were eligible. Eligible patients were assigned to receive BAT1306 (100 mg once every three weeks) plus COX inhibitor (aspirin 200 mg every day or Celebrex 400 mg every day). Chest/abdomen/pelvic CT with IV contrast will be performed to assess clinical response. The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety and duration of response. Adverse events are graded per NCI CTCAE v4.03 and will be monitored for 30 days after treatment. Patients will be followed for survival. Planned enrollment is 54 patients. Clinical trial information: NCT03638297.
A phase I/II multicenter study of ABI-009 (nab-sirolimus) combined with FOLFOX and bevacizumab as first-line (1L) therapy in patients (pts) with metastatic colorectal cancer (mCRC) with or without PTEN loss.
Authors: Sharma Sunil , Becerra Carlos Roberto , Matrana Marc Ryan , Alistar Angela Tatiana , Chiorean E. Gabriela , Schmid Anita Nagypal , Grigorian Berta , Hou Shihe , Desai Neil 
Published: January 2019

TPS730 Background: Very few treatment options are available for pts with mCRC beside the standard of care (SOC), 5-FU based chemotherapy + bevacizumab. Immunotherapy is an option for pts with microsatellite instability (~5% of mCRC). The central role of the PI3K/mTOR pathway in cancer biology, including CRC, suggests that mTOR inhibition along with chemotherapy may improve antitumor activity in the metastatic setting. A recent phase I/II study showed promising antitumor activity of everolimus + SOC as 1L treatment for mCRC (96% progression-free [PF] rate at six months at the maximum tolerated dose (MTD), and 86% ORR for pts with PTEN loss (Gilcrease, ASCO 2012). The goal of this prospective, single arm phase I/II study is to evaluate the efficacy and safety of ABI-009, a novel mTOR inhibitor, + SOC as 1L treatment for mCRC. Methods: Eligible pts have an ECOG performance status of 0-2 and histologically confirmed measurable metastatic disease. PTEN loss (by IHC) and mutational status for PIK3CA, KRAS, NRAS, BRAF by NGS is evaluated for all pts. ABI-009 is given weekly x3 every four weeks starting at 30 mg/m2and can escalate to 45 and 60 mg/m2 (3+3 design); mFOLFOX6 + bevacizumab is given every two weeks. After six cycles of therapy, cycles may change to 21-days: ABI-009 weekly x2 every three weeks and mFOLFOX6 + bevacizumab every three weeks. Pts are treated until disease progression. Tumor response is assessed by CT at baseline then every eight weeks for one year, then every 12 weeks thereafter. Phase I will enroll up to 18 pts; the primary endpoints are dose-limiting toxicities and MTD, secondary endpoints include disease control rate (DCR). Phase II will enroll 40 pts; the primary endpoint is PF rate at six months, and secondary endpoints are median PF survival, overall survival, duration of response, and DCR in the intent-to-treat population and based on PTEN status. This study is now active, with first pt enrolled. The anticipated enrollment period is 12 months. This prospective phase I/II study may show evidence of efficacy and safety of ABI-009 combined with the SOC in pts with mCRC with or without PTEN loss to warrant a larger clinical study. Results: N/A. Conclusions: N/A. Clinical trial information: NCT03439462.