Phase Ib/II study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS510-TPS510 ◽  
Author(s):  
Jared David Acoba ◽  
Amy Rock ◽  
Hing C. Wong
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Half Life ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Two Stage ◽  
Phase Ib ◽  
Advanced Phase

TPS510 Background: IL-15 is one of the most promising new candidates in cancer immunotherapy. Similar to IL-2, IL-15 stimulates natural killer (NK) and CD8+ T cells, however IL-15 may be a more effective and safer therapy as it does not trigger regulatory T cells or induce capillary leak syndrome. Preclinical data also show that IL-15 is effective in eradicating murine pancreatic cancers. However, the use of rhIL-15 in the clinic however has been limited by its short half-life (30 minutes) and cytokine related adverse effects, such as fever and hypotension. Compared with IL-15, ALT-803, a novel IL-15 superagonist complex (IL-15N72D:IL-15RαSu/Fc), has a prolonged serum half-life and is capable of potently inducing NK and CD8+ T cell proliferation in vivo. Pancreatic cancer remains one of the most common causes of cancer death and novel therapies are needed. This study represents the first clinical experience of ALT-803 in the treatment of pancreatic cancer. Methods: This is a Phase Ib/II, multi-institution study of ALT-803 in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic cancer. The study involves a phase Ib dose escalation phase to determine the MTD using a standard 3+3 design. Patients will receive gemcitabine 1,000 mg/m2 and nab-paclitaxel 125 mg/m2 D1, 8, 15 and ALT-803 at assigned dose on D2, 9, 16 of a 28d cycle. Primary endpoints are safety and tolerability. Phase II will be a two-stage expansion phase using a Simon two-stage design with a primary endpoint of survival at 8.5 months. Secondary endpoints include response rate, progression free survival, and overall survival. Response will be assessed q8 weeks by RECIST v1.1. Major inclusion criteria include: locally advanced (Phase Ib only) or metastatic pancreatic adenocarcinoma, adequate organ function, PS ECOG 0-2, and 0 or 1 (Phase Ib only) line of prior therapy for advanced pancreatic cancer. Prior nab-paclitaxel is not allowed Current enrollment: Enrollment to the first dose level is ongoing. Complete accrual of phase Ib is expected within nine months. Clinical trial information: NCT02559674.

Effect of neoantigen reactive T cells combined with chemotherapy and radiation on survival in advanced pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15756-e15756
Author(s):  
Qin Liu ◽  
Zhengyun Zou ◽  
Baorui Liu ◽  
Weiwei Kong ◽  
Fangjun Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Standard Regimen ◽  
Free Survival ◽  
Therapeutic Modalities ◽  
Lymphocyte Transfer

e15756 Background: Pancreatic cancer (PC) is one of the most aggressive and death-relating malignancy. Gemcitabine (GEM) is the key agent in the first-line standard regimen for advanced PC, which is mostly diagnosed at advanced stage and unsuitable for curative resection. The objective responsive rate (ORR) and medium progression free survival (PFS) of various GEM-based regimens are still unsatisfied. Therefore, development of new therapeutic modalities, including immunotherapy, is needed. This study is to investigate the efficacy, safety and clinical beneficial of combination neoantigen based immunotherapy with GEM and radiotherapy in locally advanced and metastatic PC patients. Methods: Three locally advanced unresectable and seven metastatic PC patients received at least two cycles of GEM (1000mg/m2 on day 1 and day 6), radiotherapy combing with neoantigen induced DC vaccination on day 7 and cytotoxic T lymphocyte transfer from day 12 to 15 (repeated every 21 days). The locally advanced unresectable PC patients received stereotactic body radiotherapy (SBRT) with a total amount of 50-66Gy during the first cycle. For metastatic patients, their partial lesions received a low dose radiation (0.5Gy bid*2days ) on day 10 and 11 in each cycle. Results: Two cases were observed with partial remission (PR), five with stable disease (sd), and three with progressive disease (PD). The disease control rate (DCR) was 70%. Median progression free survival (PFS) was 6.4 months. After the first treatment cycle, the total effectiveness for pain easement and increasing appetite are 100% (8/8)and 66.7%, respectively. Haematotoxicities with a 40% incidence rate were the most common adverse drug reactions. Two patients had grade 1 to 2 neutropenia, two with grade 3 to 4 thrombocytopenia. Three patients suffered grade 1 to 2 gemcitabine-induced skin rash. No treatment-related mortality occurred. Conclusions: Neoantigen reactive T cells combined chemoradiotherapy demonstrated an acceptable response and safety in advanced pancreatic cancer patients.

PANOVA: A pilot study of TTFields concomitant with gemcitabine for front-line therapy in patients with advanced pancreatic adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 269-269 ◽  
Author(s):  
Fernando Rivera ◽  
Javier Gallego ◽  
Carmen Guillen ◽  
Manuel Benavides ◽  
Jose A. Lopez-Martin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Electric Fields ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Grade 3 ◽  
Advanced Pancreatic Adenocarcinoma

269 Background: TTFields are alternating electric fields delivered to the region of the tumor by means of non-invasive transducer arrays. TTFields interfere with mitotic spindle formation, thus having an anti-mitotic activity. In pancreatic cancer, TTFields decreased proliferation and clonogenic potential in vitro, and reduced tumor volume in vivo. The PANOVA trial was designed to test TTFields, combined with chemotherapy, in pancreatic cancer. Methods: Twenty patients with advanced pancreatic adenocarcinoma were enrolled in a prospective, single arm study of TTFields at 150 kHz, concomitant with standard weekly gemcitabine. All patients had histologically-confirmed unresectable tumors, with an ECOG performance score of 0-1 and no prior chemotherapy or radiation therapy. The primary endpoint was incidence and severity of treatment emergent adverse events (AEs). Secondary endpoints included progression free survival (PFS), PFS rate at 6 months, overall survival (OS) and response rate. Results: The median age was 73 (range – 49-81) and 60% of the patients were females. Most patients (80%) had an ECOG score of 1. Twelve patients (60%) had distant metastases, while the others had locally advanced disease. Median compliance with TTFields was 78% (14 hours/day), with median duration of 5 months. Fourteen patients (70%) had serious (grade 3-5) AEs during the study period. Six patients (30%) had hematological, 45% gastrointestinal and 15% pulmonary AEs. Ten patients (50%) had treatment-related skin toxicity, of which only 2 were grade 3, both resolved with appropriate treatment. No TTFields-related serious AEs were reported. The median PFS was 8.3 months (95% CI 4.3, 10.3). PFS rate at 6 months was 56%. Of the evaluable tumors, 30% had partial response and another 30% stable disease. The median OS was 14.9 months and 1-year survival rate was 55%. Conclusions: TTFields concomitant to gemcitabine are tolerable and safe for advanced pancreatic cancer patients. The efficacy results are promising and support further research in this indication. An extension of the PANOVA protocol, including 20 additional patients who receive gemcitabine, nab-paclitaxel and TTFields is ongoing. Clinical trial information: NCT01971281.

scholarly journals Failure patterns and outcomes of dose escalation of stereotactic body radiotherapy for locally advanced pancreatic cancer: a multicenter cohort study

2020 ◽  
Vol 12 ◽  
pp. 175883592097715
Author(s):  
Xiaofei Zhu ◽  
Yangsen Cao ◽  
Tingshi Su ◽  
Xixu Zhu ◽  
Xiaoping Ju ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Multicenter Cohort Study ◽  
Failure Patterns ◽  
Kaplan Meier ◽  
Prescription Dose ◽  
Contrast Ct

Objective: This study aims to compare recurrence patterns and outcomes of biologically effective dose (BED10, α/β = 10) of 60–70 Gy with those of a BED10 >70 Gy for locally advanced pancreatic cancer (LAPC). Methods: Patients from three centers with a biopsy and a radiographically proven LAPC were retrospectively included and data were prospectively collected from June 2012 to June 2019. Radiotherapy was delivered by stereotactic body radiation therapy. Recurrences were categorized as in-field, marginal, and outside-the-field recurrence. Patients in two groups were required to receive abdominal enhanced contrast CT or MRI every 2–3 months and CA19-9 examinations every month during follow-up. Treatment-related toxicities were evaluated every month. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: After propensity score matching, there were 486 patients in each group. The median prescription dose of the two groups was 37 Gy/5–8 f (range: 36–40.8 Gy/5–8 f) and 42 Gy/5–8 f (range: 40–49.6 Gy/5–8 f), respectively. The median OS of patients with a BED10 >70 Gy and a BED10 60–70 Gy was 20.3 months (95% CI: 19.1–21.5 months) and 18.2 months (95% CI: 17.8–18.6 months) respectively ( p < 0.001). The median PFS of the two cohorts was 15.4 months (95% CI: 14.2–16.6 months) and 13.3 months (95% CI: 12.9–13.7 months) respectively ( p < 0.001). A higher incidence of in-field and marginal recurrence was found in patients with BED10 of 60–70 Gy (in-field: 97/486 versus 72/486, p = 0.034; marginal: 109/486 versus 84/486, p = 0.044). However, more patients with BED10 >70 Gy had grade 2 or 3 acute (87/486 versus 64/486, p = 0.042) and late gastrointestinal toxicities (77/486 versus 55/486, p = 0.039) than those with BED10 of 60–70 Gy. Conclusion: BED10 >70 Gy was found to have the best survival benefits along with a higher incidence of acute and late gastrointestinal toxicities. Therefore, a higher dose may be required in the case of patients’ good tolerance.

scholarly journals Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Mao Lin ◽  
Xiaoyan Zhang ◽  
Shuzhen Liang ◽  
Haihua Luo ◽  
Mohammed Alnaggar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
T Cell ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Antitumor Efficacy ◽  
Γδ T Cell ◽  
Group A

Abstract Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits. ClinicalTrials.gov ID: NCT03180437.

Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer

2009 ◽  
Vol 27 (33) ◽  
pp. 5513-5518 ◽  
Author(s):  
David Cunningham ◽  
Ian Chau ◽  
Deborah D. Stocken ◽  
Juan W. Valle ◽  
David Smith ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Primary Outcome Measure ◽  
Phase Iii ◽  
Open Label

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

scholarly journals Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jakob Liermann ◽  
Patrick Naumann ◽  
Fabian Weykamp ◽  
Philipp Hoegen ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Free Survival ◽  
Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

scholarly journals The clinical implication of CD45RA+ naive T cells and CD45RO+ memory T cells in advanced pancreatic cancer: A proxy for tumor biology and outcome prediction.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 196-196
Author(s):  
Junjie Hang ◽  
Lixia Wu ◽  
Kequn Xu
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cancer Progression ◽  
Cox Regression ◽  
Memory T Cells ◽  
Tumor Biology ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Student’S T

196 Background: Naive and memory T cells play a pivotal role in solid tumor pathogenesis but their role in pancreatic cancer progression remains elusive. Thus, we aimed to investigate their clinical potential in advanced pancreatic cancer (APC). Methods: Flow cytometry was performed to evaluate the level of peripheral naive and memory T cells from APC patients. Interrelationships between naive, memory T cells and clinicopathological variables were evaluated using pearson’s correlation. The prognostic impact of naive and memory T cells were assessed by Kaplan-Meier analysis and Cox regression. The correlation between naive/memory T cells and tumor progression was investigated by Student’s t test. Results: CD4+ naive/memory ratio showed close correlations with hemoglobin, red blood cell (RBC), absolute neutrophil count (ANC) and platelet while CD8+ naive/memory ratio was correlated with hemoglobin, RBC and CEA. Higher baseline lever of CD4+CD45RO+/CD4+ was correlated with better overall survival (OS) (P = 0.036). Patients with CD4+ naive/memory ratio ≥ 0.36 had a poorer OS than those with CD4+ naive/memory ratio < 0.36 (P = 0.021). In addition, CD4+ naive/memory ratio showed independent prognostic impact (HR 1.427, 95%CI 1.033-1.973, P = 0.031). Furthermore, poorer clinical response was correlated with higher level of CD8+ naive/memory ratio after the third cycle of chemotherapy (P = 0.01). Besides, patients with an low level of CD8+ naive/memory ratio had longer progression-free survival (PFS) (P = 0.028). Conclusions: We propose CD4+ naive/memory ratio as a novel prognostic biomarker for APC. In addition, CD8+ naive/memory ratio can be a candidate marker for predicting PFS and the change of its level may reflect the progression of APC.

Comparison of concurrent chemoradiotherapy and chemotherapy alone for locally advanced pancreatic cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 351-351 ◽  
Author(s):  
Younak Choi ◽  
Tae-Yong Kim ◽  
Do-Youn Oh ◽  
Kyubo Kim ◽  
Eui Kyu Chie ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Outcomes ◽  
Palliative Chemotherapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Positive Lymph Node ◽  
Locally Advanced Pancreatic Cancer ◽  
Hematologic Toxicity

351 Background: The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), especially the role of chemoradiotherapy (CCRT), is still in debate. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with LAPC. Methods: We consecutively enrolled LAPC patients treated between 2003 and 2010. AJCC 7th edition was followed for the diagnostic criteria of LAPC. We retrospectively evaluated the clinical outcomes according to treatment groups (CCRT vs CA). Results: A total of 86 patients were enrolled. Median age was 60 years. ECOG PS was 0-1 in 77 (89.5%) and 2 in 9 (10.5%). Forty five patients (52.3%) were treated with CCRT and 41 patients (47.7%) with CA. Baseline characteristics were not significantly different between CCRT and CA group. In the CCRT group, gemcitabine (n=7, 15.6%), 5-FU (n=10, 22.2%), and capecitabine (n=28, 62.2%) were concurrently used with radiation. Radiation was delivered with 55.8Gy/ 31fraction. All of the CA group patients were treated with gemcitabine-based chemotherapy. Median progression free survival (PFS) and overall survival (OS) of whole patients were 6.9 months [95%CI 4.8-9.0] and 12.7 months [95%CI 11.6-14.3]. PFS and OS of CCRT versus CA was 8.9 months [95%CI 6.8-11.0] vs 3.7 months [95%CI 2.9-4.5] (p<0.001) and 15.8 months [95%CI 13.5-18.1] vs 11.3 months [95%CI 9.3-13.3] (p=0.017). In multivariate analysis, tumor size (≥3cm), positive lymph node, elevated CA 19-9, decreased serum albumin and CCRT was significant for PFS and OS (adjusted hazard ratio of CCRT was 0.424 (p=0.002) in PFS and 0.472 (p=0.014) in OS). Grade 3-4 hematologic toxicity was less frequent during CCRT period (p=0.002). Conclusions: In LAPC, patients who received CCRT show better OS and PFS compared with patients who were treated with palliative chemotherapy alone. It’s worthy to further study the role of CCRT in LAPC.

Clinical study of nab-paclitaxel in combination with S-1 as first-line therapy in patients with advanced pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15765-e15765 ◽  
Author(s):  
Yi Hu ◽  
Danyang Sun
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Medical Center ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Standard Regimen ◽  
First Line Therapy ◽  
Line Therapy

e15765 Background: Pancreatic cancer is one of the highest cancer-mortality diseases worldwide with limited treatment. Most patients had local advanced or metastatic disease at the time of diagnosis. Gemcitabine-based therapy has been standard regimen in the past few decades. It is necessary to find new strategies of treatment. Methods: The aim of this study was to evaluate the efficacy and safety of nab-paclitaxel in combination with S-1 as first-line therapy in advanced pancreatic cancer. We retrospectively evaluated 79 patients with advanced pancreatic cancer from 2014 to 2016 treated in our medical center. All the patients received at least two cycles of combination therapy. Nab-paclitaxel was administered 260mg/ m2 as a total dose on day 1 and 5 or on day 1 and 8. S-1 was administered orally twice a day for 14 days according to body surface area. S-1 monotherapy was administered as maintenance treatment after 6 to 8 cycles of combination therapy until the progression of disease. Results: In all the 79 patients enrolled, the median age was 56, range from 36 to 77, 56 (70.9%) patients had KPS 90, 58 (73.4%) patients had multiple metastatic sites. The overall response rate was 51.9%; median progression-free survival was 5.7 months (95%CI 5.010-6.292); median overall survival was 11.9 months (95%CI 9.731-13.990). The efficacy of CA19-9 decrease > 50% was significant higher compared with those of CA19-9 decrease < 50%. Treatment was well tolerated. Grade 4 toxicity was only reported in neutropenia of 5 patients. Grade 3 adverse events include neutropenia in patients (13.9%), nausea and vomiting in one patient (1.3%), peripheral sensory in one patient (1.3%) and alopecia in 3 patients (3.8%). Conclusions: Nab-paclitaxel in combination with S-1 as first-line therapy demonstrated promising antitumor activity and well-tolerated toxicities and presents a new alternative for locally advanced and metastatic pancreatic cancer.

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