Prospective phase I study of nab-paclitaxel plus gemcitabine with concurrent MR-guided IMRT in patients with locally advanced or borderline resectable pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS480-TPS480
Author(s):  
Jeffrey R. Olsen ◽  
Parag J. Parikh ◽  
Todd A. DeWees ◽  
Lindsey Olsen ◽  
William G. Hawkins ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Locally Advanced ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Cine Mr ◽  
Patient Reported

TPS480 Background: Radiotherapy (RT) for locally advanced and borderline resectable pancreatic cancer (LABPC) is controversial as potential local control benefits are often obscured by high rates of distant progression. However, local failure remains a significant cause of morbidity among patients without distant progression after initial chemotherapy, although toxicity concerns may limit delivery of optimal systemic therapy concurrent with RT. Given known systemic efficacy and radiosensitization effects of nab-paclitaxel (A) with gemcitabine (G), we initiated a phase I study of nab-paclitaxel with gemcitabine (AG) and concurrent intensity modulated radiation therapy with magnetic resonance guidance (MR-IMRT) for LABPC. Methods: A planned 24 patients with LABPC will be enrolled to a phase I dose escalation trial using the Time-to-Event Continual Reassessment Method (TITE-CRM) design. Following one lead-in cycle of GA, MR-IMRT is administered daily with concurrent weekly GA for a total of 25 fractions in 5 weeks. The initial dose levels for RT and AG, respectively, are: 40 Gy MR-IMRT, 75 mg/m2 A and 600mg/m2 G. The maximum possible dose level is 60 Gy MR-IMRT, 100mg/m2 A and 1000mg/m2 G. To reduce toxicity risk, MR-IMRT volumes include the primary tumor only, with cine-MR used for intra-fraction tumor tracking in place of fiducial markers. The primary endpoint is determination of the maximum tolerated dose level, with secondary endpoints including rate of conversion to resectable disease, progression- free survival, overall survival, and patient reported quality of life. Clinical trial information: NCT02283372.

scholarly journals Phase I Study of Nab–Paclitaxel plus Gemcitabine as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer

2017 ◽  
Vol 37 (2) ◽  
pp. 853-858 ◽  
Author(s):  
KEN-ICHI OKADA ◽  
SEIKO HIRONO ◽  
MANABU KAWAI ◽  
MOTOKI MIYAZAWA ◽  
ATSUSHI SHIMIZU ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Neoadjuvant Therapy ◽  
Phase I Study ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer

Management of Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma

2019 ◽  
Author(s):  
Francis Igor Macedo ◽  
Danny Yakoub ◽  
Vikas Dudeja ◽  
Nipun B. Merchant
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
The United States ◽  
Locally Advanced Pancreatic Cancer ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Number Of Patients

The incidence of pancreatic cancer continues to rise, and it is now the third-leading cause of cancer-related deaths in the United States. Only 15 to 20% of patients are eligible to undergo potentially curative resection, as most tumors are deemed unresectable at the time of diagnosis because of either locally advanced disease or distant metastases. Improvements in preoperative CT imaging have enabled better determination of the extent of disease and allowed for better operative planning. Based on their relationship to the surrounding vasculature and structures and presence or absence of distant disease, pancreatic tumors are classified into four categories: resectable, borderline resectable pancreatic cancer (BRPC), locally advanced pancreatic cancer (LAPC), and metastatic. With the recent advent of more effective chemotherapy regimens, efforts have focused on using neoadjuvant therapy approaches to increase the likelihood of achieving an R0 in patients with BRPC and possibly convert unresectable, locally advanced tumors to potentially resectable tumors. Response with neoadjuvant therapy regimens has resulted in increased number of patients eligible for resection, many times requiring vascular resection. Herein, we describe recent changes in the classification, important surgical and pathologic considerations and updated multimodal therapeutic options in the complex management of BRPC and LAPC.  This review contains 5 figures, 2 tables, and 78 references. Key Words: borderline resectable pancreatic cancer, CA 19-9, FOLFIRINOX, locally advanced pancreatic cancer, nab-paclitaxel, neoadjuvant chemotherapy, pancreatectomy, portal vein resection, radiation therapy, gemcitabine

Phase I study of veliparib with gemcitabine and radiation therapy in patients with borderline resectable and locally advanced unresectable pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS487-TPS487 ◽  
Author(s):  
Richard Tuli ◽  
Nicholas N. Nissen ◽  
Alagappan Annamalai ◽  
David M. J. Hoffman ◽  
Miranda Bryant ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Repair ◽  
Phase I ◽  
Phase I Study ◽  
Proportional Hazards Model ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Tumor Control ◽  
Clinical Activity ◽  
Borderline Resectable

TPS487 Background: Targeted inhibition of PARP1/2 is one way to further exploit the well-known synergy between gemcitabine (G) and radiotherapy (RT) in locally advanced pancreatic cancer (LAPC). PARP1/2 inhibitors, such as veliparib (V), have shown excellent anti-tumor activity when used with other cytotoxic therapies. This synergy may be further exploited in pancreatic cancer by targeting tumors with pre-existing defects in double- strand DNA repair. Extrapolating from our own laboratory findings (Tuli et al, Transl Oncol, 2014) and based on our hypothesis that PARP1/2 inhibition with G and RT will result in enhanced tumor control, we are conducting an IRB- approved phase I study in patients with borderline resectable and LAPC. Methods: The primary objective of this study is to determine the maximum tolerated dose (MTD) of V, which is defined as the dose level resulting in a probability (θ = 0.4) that a dose limiting toxicity (DLT) will occur within six weeks. Treatment cycle is 3 weeks followed by weekly evaluation for an additional 3 weeks. G (1000 mg/m2) is administered on days 1, 8, 15. RT (36 Gy) is given in 15 fractions (2.4 Gy/day). V is administered BID in 20 mg increments beginning at a dose of 20 mg. Inclusion criteria: histolopathological diagnosis of borderline resectable or LAPC, age > 18 years, KPS > 70%, life expectancy > 6 months, normal organ and marrow function, and negative pregnancy test. Dose escalation follows a Bayesian escalation without control (EWOC) design, where time to DLT is modeled using a proportional hazards model with constant baseline hazard rate. Secondary objectives: 1) measure clinical activity using RECIST 1.1 for PFS, OS; 2) evaluate pre-treatment tumor biopsy specimen and longitudinal blood samples for baseline levels of DNA repair proteins (ERCC1, XRCC1, PAR, etc.) as potential prognostic, predictive and correlative biomarkers; and 3) assess BRCA1/2, PALB2, PTEN germline and somatic mutations using validated gene sequencing, immunohistochemical and quantitative PCR methods. Since December 2013, 26 patients have consented with 22 enrolled. Clinical trial information: NCT01908478.

Pathologic assessment of tumor regression after neoadjuvant therapy for locally advanced/borderline resectable pancreatic cancer

Pancreatology ◽  
2016 ◽  
Vol 16 (4) ◽  
pp. S92-S93
Author(s):  
Yoko Matsuda ◽  
Jennifer Y. Wo ◽  
Carlos Fernández-del Castillo ◽  
Lawrence S. Blaszkowsky ◽  
Cristina R. Ferrone ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Resectable Pancreatic Cancer ◽  
Borderline Resectable ◽  
Borderline Resectable Pancreatic Cancer ◽  
Pathologic Assessment
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