Clinical Trial Simulations Based on A Meta-Analysis of Studies In Patients With Locally Advanced and/or Metastatic Adenocarcinoma Pancreatic Cancer Receiving Gemcitabine (GEM) Alone or In Combination

Devimistat (CPI-613®) is a novel lipoate analog that inhibits the tricarboxcylic acid cycle at two key carbon entry points. Through its inhibition of pyruvate dehydrogenase and a-ketoglutarate dehydrogenase complexes, devimistat inhibits the entry of glucose and glutamine derived carbons, respectively. Pancreatic cancer is dependent on mitochondrial function for enhanced survival and aggressiveness. In a Phase I study of modified FOLFIRINOX, in combination with devimistat for metastatic pancreatic cancer patients, there was a 61% objective response rate including a 17% complete response rate. This report outlines the rationale and design of the AVENGER 500 study, a Phase III clinical trial of devimistat in combination with modified FOLFIRINOX compared with FOLFIRINOX alone for patients with previously untreated metastatic adenocarcinoma of the pancreas. Clinical trial registration: NCT03504423

Download Full-text

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

Radiotherapy and Oncology ◽

10.1016/j.radonc.2011.04.001 ◽

2011 ◽

Vol 99 (2) ◽

pp. 108-113 ◽

Cited By ~ 53

Author(s):

Chang-Peng Zhu ◽

Jian Shi ◽

Yue-Xiang Chen ◽

Wei-Fen Xie ◽

Yong Lin

Keyword(s):

Pancreatic Cancer ◽

Meta Analysis ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer

Download Full-text

FOLFIRINOX in locally advanced or metastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.313 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 313-313 ◽

Cited By ~ 4

Author(s):

Jason Edward Faris ◽

Theodore S. Hong ◽

Shaunagh McDermott ◽

Alexander R Guimaraes ◽

Dushyant Sahani ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Advanced Disease ◽

Locally Advanced ◽

Phase Iii ◽

Metastatic Pancreatic Cancer ◽

Clinical Trial Setting ◽

Locally Advanced Disease ◽

Grade 3 ◽

Trial Setting

313 Background: The recently published Phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability with FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX. Methods: 29 patients with locally advanced or metastatic pancreatic cancer treated with FOLFIRINOX between July 2010 and April 2011 were used for this analysis. Clinical characteristics, and gradeable toxicities were tabulated, and formal radiographic review performed to determine best overall response rates (ORR). Results: 17 patients received FOLFIRINOX for metastatic disease and 12 patients for locally advanced disease. The median age of patients was 60 (range 39-76). 22/29 patients were men. 18/29 patients had received no prior chemotherapy. There was one patient with PS 2; all others had PS 0 or 1. 8/29 patients had biliary stents. Overall, 11 partial responses (PR) were observed (ORR 38%); 10/11 partial responses were in chemo-naïve patients, who had an ORR of 56%. In the metastatic setting, there were 6 PR, for an ORR of 35%, and 7 patients with stable disease (SD). In the locally advanced setting, there were 5 PR (ORR 42%), and 7 patients with SD. Following treatment with FOLFIRINOX, one patient with locally advanced disease has subsequently undergone R0 resection. The median number of cycles performed was 8 in both the locally advanced and metastatic settings. 12/29 patients required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 10 patients; 7/10 had not received prophylactic growth factor treatment from the start of FOLFIRINOX. 4 patients developed febrile neutropenia, 4 patients developed grade 3/4 thrombocytopenia, and 1 patient developed grade 4 anemia. Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both the metastatic and locally-advanced settings. FOLFIRINOX appears to be associated with manageable, but significant toxicities, with over 40% of patients requiring hospitalization.

Download Full-text

Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.189 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 189-189

Author(s):

Avani Satish Dholakia ◽

Muhammad Ali Chaudhry ◽

Jeffrey P. Leal ◽

Daniel Tandel Chang ◽

Siva P. Raman ◽

...

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Tumor Volume ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Metabolic Tumor Volume ◽

Total Lesion Glycolysis ◽

Pet Scan ◽

Locally Advanced Pancreatic Cancer

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Livermean + (2 * Liversd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p < 0.003) and TLG of 70.9 cm3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p < 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.

Download Full-text