Interim analysis of a phase II study of dose-modified FOLFIRINOX (mFOLFIRINOX) in locally advanced (LAPC) and metastatic pancreatic cancer (MPC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 256-256 ◽  
Author(s):  
Edward Samuel James ◽  
Xiaopan Yao ◽  
Xiangyu Cong ◽  
Stacey Stein ◽  
Kristin Kaley ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Historical Data ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Sensory Neuropathy ◽  
Open Label ◽  
Grade 3 ◽  
Ecog Ps

256 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, we are conducting a prospective phase II open label study to evaluate the efficacy & tolerability of mFOLFIRINOX in pts with advanced pancreatic cancer (PC). Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX with 25% dose reductions of irinotecan & bolus 5-FU given every two wks until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. FDG-PET scans were obtained at baseline & after 2 cycles. CAT scans were obtained after every 4 cycles. Toxicities & response rate (RR) were compared to historical data reported by Conroy. Results: 53 pts with ECOG PS ≤1 have been enrolled to date between 11/11 and 08/13, Pt characteristics: LAPC 22; MPC 31; median age 62 yrs (range 46-86); male 30. Median # of cycles was 8 (range 1-21). Grade 3/4 toxicities were: anemia, febrile neutropenia (FN) & peripheral sensory neuropathy (PSN) – 3.8% each; ALT increased & thromboembolism – 5.7% each; diarrhea 7.5%; fatigue 11.3%; neutropenia 17%; thrombopenia 11.3% & vomiting 1.9%. Anemia ( p< 0.04), FN (p<0.04), PSN (p<0.04) and vomiting (p<0.02) were significantly decreased compared to historical data (Conroy). Response by RECIST (CR+PR) in 26 evaluable pts with MPC was 29% (0 CR, 9 PR, 14 SD, 3 PD) & similar to historical data (31.6%; p 0.85). 6/13 evaluable pts with LAPC underwent resection (46%).13/36 pts evaluable for PET response had a >50% decrease in SUV(max)(36%). Evaluation for OS & PFS is ongoing. Conclusions: Findings from our interim analysis suggests that mFOLFIRINOX, given along with prophylactic pegfilgrastim is associated with a similar RR and improved tolerability compared to full dose FOLFIRINOX in advanced PC. In pts with LAPC, neoadjuvant FOLFIRINOX appears to have substantial activity with 46% of evaluable pts undergoing resection. Accrual will continue to reach a goal of 70 pts. Clinical trial information: NCT01523457.

Results of conversion surgery after the triple combination chemotherapy of SOXIRI (S-1/oxaliplatin/irinotecan) in patients with unresectable pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 366-366
Author(s):  
Naoya Ikeda ◽  
Takahiro Akahori ◽  
Sohei Satoi ◽  
Hiroaki Yanagimoto ◽  
Minako Nagai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Clinical Impact ◽  
Ductal Adenocarcinoma ◽  
Unresectable Pancreatic Cancer ◽  
Conversion Surgery ◽  
Open Label ◽  
Grade 3 ◽  
Medical University

366 Background: Recent improvements in chemotherapy for initially unresectable pancreatic ductal adenocarcinoma (UPDAC) occasionally show remarkable antitumor effect and lead to conversion surgery (CS). However, the optimal indication and clinical impact of CS remains unknown. We have recently developed a new regimen consisted of biweekly S-1, oxaliplatin, and irinotecan (SOXIRI). In this regimen, we used S-1 in alternate-day administration instead of 5-FU, that can be more feasible than FOLFIRINOX. The aim of this study was to evaluate the clinical impact of CS after SOXILI treatment for initially UPDAC. Methods: We conducted an open-label, single-arm, phase II study that was carried out at Nara Medical University and Kansai Medical University in Japan. Patients with untreated metastatic and locally advanced PDAC were enrolled. They received 80 mg/m2 twice a day of S-1 for 2 weeks in alternate-day administration, 150 mg/m2 of irinotecan on day 1, and 85 mg/m2 of oxaliplatin on day 1 of a 2-week cycle. Results: The 35 enrolled patients received a median of six (range: 2-15) treatment cycles. The RR was 22.8%; median OS, 17.7 months; and median PFS, 7.4 months. Major grade 3 or 4 toxicity included neutropenia (54%), anemia (17%), febrile neutropenia (11%), anorexia (9%), diarrhea (9%), and nausea (9%). Twenty-three out of 35 patients of UR-PDAC were unresectable locally advanced pancreatic cancer (UR-LAPA). Seven out of 23 patients with UR-LAPA underwent CS. Distal pancreatectomy with celiac axis resection was performed in three patients, central pancreatectomy was performed in one patient. Pancreatoduodenectomy (PD) was performed in two patients, and PD with portal vein resection in one patient. Two out of seven patients had postoperative complications. One case had grade B pancreatic fistula, and the other case underwent cholecystectomy due to acute cholecystitis. The median OS in patients who received CS was 31.4 months. Conclusions: SOXIRI regimen has shown promising clinical efficacy with acceptable tolerability in patients with unresectable pancreatic cancer. Furthermore, it may be a potent first-line treatment when considering conversion surgery. Clinical trial information: UMIN000014339.

Phase I/II study of PCI-27483, a coagulation factor VIIa (FVIIa) inhibitor in patients with advanced pancreatic cancer receiving treatment with gemcitabine.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 221-221 ◽  
Author(s):  
R. K. Ramanathan ◽  
V. Gressler ◽  
S. Shah ◽  
D. Loury ◽  
A. Hamdy ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Coagulation Factor ◽  
Hematologic Toxicity ◽  
Venous Thromboembolic Events ◽  
Grade 3 ◽  
To Receive

221 Background: PCI-27483 is a selective inhibitor of FVIIa, a serine protease activated by interaction with tissue factor (TF). TF upregulation in tumor cells correlates with angiogenesis and a worsened prognosis. Hydrolysis of protease activated receptors by the TF:FVIIa complex induces up-regulation of IL-8 and VEGF. PCI-27483 inhibited the growth of human pancreatic tumors in animal models at a 2.5x to 3.0x change in prothrombin time. PK/INR relationships from a phase I study in healthy volunteers were used to select initial doses of PCI-27483 for the current study. Methods: Patients (pts) with locally advanced or metastatic pancreatic cancer, ECOG performance status 0-1, and normal coagulation were enrolled. All pts in phase I and II receive gemcitabine (G) as a 30-min IV infusion at a dose of 1000 mg/m2 on 3 out of every 4 wks. PCI-27483 is administered twice daily by SC injection. In phase I, doses of PCI-27483 were intra-patient escalated (0.8 to1.2 to1.5 mg/kg) over 4 to 8 wks. The targeted peak INR, measured 2 h postdose, was 3.0. In phase II, pts are being randomized to a control arm to receive G only or to a PCI-27483 arm to receive G plus PCI-27483. Phase I pts receiving 80% of planned doses during in first 6 wks were considered evaluable. Spiral CT scans are performed at 8-wk intervals. Study endpoints: adverse event profile, progression-free survival, venous thromboembolic events, and overall survival. Results: Phase I—8 pts enrolled, 5 pts evaluable. Highest dose of PCI- 27483 achieved was 0.8 mg/kg for 2 pts, 1.2 mg/kg for 3 pts and 1.5 mg/kg for 3 pts. Hematologic toxicity: grade 3 neutropenia (n= 1) or anemia (n = 2). Other grade 3 toxicities: elevated INR (n = 4) or elevated aPTT (n = 1). Dose-level-specific mean 2-h INR values were 2.2 at 0.8 mg/kg (CV=9%; n=7), 3.2 at 1.2 mg/kg (CV=33%; n=6) and 2.9 at 1.5 mg/kg (CV=16%; n=3). No VTEs occurred. Radiologic evaluations of 5 evaluable pts: 4 SD at 16 wks (1st pt SD for >40 wks; 5th pt SD at 8 wks, 16-wk scan pending). Conclusions: PCI-27483 is well tolerated at doses up to 1.5 mg/kg bid with G 1,000 mg/m2. Sustained SDs occurred and INRs were generally within the expected range. The randomized phase II study is ongoing at a dose of 1.2 mg/kg bid. [Table: see text]

A phase II trial of the effect of perindopril on hand foot syndrome (HFSR) incidence and severity in patients receiving regorafenib with refractory metastatic colorectal carcinoma (mCRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 824-824
Author(s):  
Barbara L. Melosky ◽  
Howard John Lim ◽  
Janine Davies ◽  
Sharlene Gill ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Phase Ii ◽  
Interim Analysis ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Capillary Endothelium ◽  
Open Label ◽  
Grade 3 ◽  
Overall Survival Benefit ◽  
Ecog Ps

824 Background: Regorafenib is an oral multi-kinase inhibitor (MKI), with a demonstrated overall survival benefit in mCRC refractory to standard therapy ( PMID 23177514). The most common grade 3 adverse event (AE) reported in this trial was HFSR, with 47% of patients (pts) experiencing HFSR of all grades, and 17% with grade 3 severity. The pathogenesis of regorafenib-induced HFSR is not well established, but may be related to alterations in the capillary endothelium. Perindopril is an Angiotensin Converting Enzyme (ACE) Inhibitor indicated for the treatment of hypertension, and may also play a role in preventing endothelial dysfunction ( PMID 17140552). We hypothesized that perindopril may prevent or reduce the severity of regorafenib-induced HFSR. Methods: In this single center Phase II, open label trial, 34 pts with refractory mCRC were planned to be treated with regorafenib (160 mg/day) and perindopril (4 mg/day) with both agents given 3 weeks on and 1 week off. An interim analysis was planned after 10 evaluable pts. The primary objective was to assess the proportion of pts with any grade HSFR toxicity. Secondary endpoint included time to development of worst (grade 3) HSFR toxicity, proportion of all grades of hypertension and all grade toxicities, and progression free survival. All toxicities were evaluated using CTCAE v4.03. Results: 12 pts were accrued over a 9 month time period, and 10 pts were considered evaluable as they completed one cycle of treatment. Pt characteristics included (6 M/ 6F, mean age 62, ECOG PS 0 (25%)/ 1 (75%). A planned interim analysis was performed after 10 evaluable pts had completed their first cycle of study treatment. 5/10 (50%) experienced Grade 3 HFSR, and based on the statistical plan it was deemed highly unlikely that perindopril would lead to reduced levels of regorafenib induced HSFR compared with regorafenib alone thus enrolment was stopped. The most frequent other grade 3 toxicities included hypertension (16.7%), and increased AST (16.7%). Conclusions: The addition of perindopril to regorafenib did not appear to reduce HSFR incidence and severity in pts with refractory mCRC. Clinical trial information: NCT02651415.

EXIBIT: An international multicenter phase II trial of gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4135-4135 ◽  
Author(s):  
T. André ◽  
J. M. Reyes-Vidal ◽  
L. Fartoux ◽  
P. Ross ◽  
M. Leslie ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Bile Ducts ◽  
Locally Advanced ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Extrahepatic Bile Ducts ◽  
Grade 3 ◽  
Ecog Ps

4135 Background: Biliary tract carcinomas (BTC) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) showed promising activity in a French Phase II study (4 centers) in advanced BTC (André. Ann Oncol 2004;15:1339–1343). The objective of this study is to further evaluate the efficacy and safety of GEMOX as first-line therapy in patients (pts) with advanced BTC. Methods: Eligible pts were >18 years of age with histologically proven and measurable, locally advanced or metastatic BTC, had an ECOG PS ≤ 2, adequate renal and hematologic functions, bilirubin < 2.5 × upper limit of normal, and no prior malignancy or brain metastases. Gemcitabine 1000 mg/m2 (Day 1) and oxaliplatin 100 mg/m2 (Day 2) were administered every 2 weeks. The primary objective was response rate (RR) by RECIST (one dimension); secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Here we report an interim analysis of OS and safety. Results: A total of 70 pts were enrolled between April 2003 and April 2005. The median age was 62 years (range 30–83), 40.0% of pts were male, 94.3% had ECOG PS 0–1. Tumor sites were intrahepatic bile ducts (37.1%), gallbladder (31.4%), extrahepatic bile ducts (12.9%), ampulla of Vater (1.4%), intra/extrahepatic bile ducts (1.4%), missing data (15.7%); 98.6% of pts had no prior radiotherapy and 50% had no prior surgery for BTC. Median OS is 8.25 months (68% of pts are dead and 32% have censored data). Sixty-seven pts were evaluable for safety. Grade 3/4 (NCI-CTC v. 2) hematologic toxicities (% of pts) included thrombocytopenia 10.4%, anemia 9.0%, and neutropenia 9.0%. One pt had febrile neutropenia. Grade 3/4 nonhematologic toxicities included pain 10.4%, ALT elevation 9.0%, fatigue 9.0%, infection 10.4%, vomiting 9.0%, sensory neuropathy 4.5%, nausea 4.5%, and diarrhea 3.0%. One patient died during treatment (cause unknown). Conclusions: GEMOX has acceptable toxicity in pts with BTC. Updated efficacy data (RR, PFS, and OS for the entire population and also by tumor sites) will be presented at the meeting. [Table: see text]

Single-institution experience with FOLFIRINOX in advanced pancreatic cancer (PC).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 330-330 ◽  
Author(s):  
Krishna Soujanya Gunturu ◽  
Jaykumar Ranchodbhai Thumar ◽  
Howard S. Hochster ◽  
Stacey Stein ◽  
Xiaopan Yao ◽  
...  
Keyword(s):  
Historical Data ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Cancer Center ◽  
Clinically Significant ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Ecog Ps ◽  
The Impact ◽  
Dose Reductions

330 Background: FOLFIRINOX provides clinically significant benefit in advanced PC compared to gemcitabine (Conroy et al. New Engl J Med 2011;364:1817). Despite superior efficacy, toxicities have tempered enthusiasm for FOLFIRINOX and limited its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our experience with FOLFIRINOX in pts with advanced PC. Methods: We performed a retrospective review of dose, toxicity, efficacy of FOLFIRINOX in all pts with locally advanced unresectable PC (LAPC) and metastatic PC (MPC) treated with FOLFIRINOX at Yale Cancer Center between 06/10 and 06/11. Dose attenuations were at the treating physician’s discretion. All pts received prophylactic pegfilgrastim. Pts were treated until progression, unacceptable toxicity, or surgical resection. Toxicities and efficacy were compared to historical data reported by Conroy. Results: 31 pts with ECOG PS 0 or 1 were treated. Pt characteristics: LAPC 15; MPC 16; median (med) age 60 yrs (range 48-78); male 11; prior chemotherapy 5 (adjuvant 3). Med number of cycles received was 6 (range 1-18). Only 5 pts received full doses of all drugs with cycle 1. Dose reductions with cycle 1 were: IRI 26 pts, OX 10 pts, bFU 10 pts, infusional FU 1 pt. b5FU was omitted in 6 pts. Med relative dose intensities were: OX 88%, IRI 64%, b-FU 57%, infusional FU 100% (compared to OX 78%, IRI 81%, and FU 82% [Conroy]). The % of pts with grade 3 or 4 toxicities was: fatigue or mucositis, 9.6%; dehydration or neutropenia 6.4%; vomiting, thromboembolism, febrile neutropenia, thrombopenia or anemia, 3.2%. Neutropenia (p<0.0001), diarrhea (p<0.03), fatigue (p<0.02) were significantly decreased compared to historical data (Conroy). Response (CR+PR) in 30 evaluable pts was 33% (1 CR, 9 PR, 14 SD, 6 PD) and similar to historical data (31.6%; p 0.21). 2 pts with LAPC underwent resection. Evaluation for OS and PFS is ongoing. Conclusions: Our findings suggest that dose attentuation of FOLFIRINOX, esp IRI and bFU, with prophylactic pegfilgrastim is associated with improved tolerability and equivalent response rate compared to full dose FOLFIRINOX in advanced PC. The impact of dose attenuations on toxicity and efficacy warrants further evaluation in both LAPC and MPC.

scholarly journals Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer

2015 ◽  
Vol 33 (13) ◽  
pp. 1475-1481 ◽  
Author(s):  
Mitesh J. Borad ◽  
Shantan G. Reddy ◽  
Nathan Bahary ◽  
Hope E. Uronis ◽  
Darren Sigal ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Tumor Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Randomized Phase Ii ◽  
Grade 3

Purpose TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned 1:1:1 to gemcitabine (1,000 mg/m2), gemcitabine plus TH-302 240 mg/m2 (G+T240), or gemcitabine plus TH-302 340 mg/m2 (G+T340). Randomized crossover after progression on gemcitabine was allowed. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), tumor response, CA 19-9 response, and safety. Results Two hundred fourteen patients (77% with metastatic disease) were enrolled between June 2010 and July 2011. PFS was significantly longer with gemcitabine plus TH-302 (pooled combination arms) compared with gemcitabine alone (median PFS, 5.6 v 3.6 months, respectively; hazard ratio, 0.61; 95% CI, 0.43 to 0.87; P = .005; median PFS for metastatic disease, 5.1 v 3.4 months, respectively). Median PFS times for G+T240 and G+T340 were 5.6 and 6.0 months, respectively. Tumor response was 12%, 17%, and 26% in the gemcitabine, G+T240, and G+T340 arms, respectively (G+T340 v gemcitabine, P = .04). CA 19-9 decrease was greater with G+T340 versus gemcitabine (−5,398 v −549 U/mL, respectively; P = .008). Median OS times for gemcitabine, G+T240, and G+T340 were 6.9, 8.7, and 9.2 months, respectively (P = not significant). The most common adverse events (AEs) were fatigue, nausea, and peripheral edema (frequencies similar across arms). Skin and mucosal toxicities (2% grade 3) and myelosuppression (55% grade 3 or 4) were the most common TH-302–related AEs but were not associated with treatment discontinuation. Conclusion PFS, tumor response, and CA 19-9 response were significantly improved with G+TH-302. G+T340 is being investigated further in the phase III MAESTRO study (NCT01746979).

A phase I trial of S-1 with concurrent radiotherapy for locally advanced pancreatic cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14003-14003
Author(s):  
M. Ikeda ◽  
T. Okusaka ◽  
Y. Ito ◽  
H. Ueno ◽  
C. Morizane ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Maximum Tolerated Dose ◽  
Locally Advanced Pancreatic Cancer ◽  
Hematological Toxicity ◽  
Concurrent Radiotherapy ◽  
Grade 3

14003 Background: S-1 is a novel oral fluoropyrimidine derivative, and a phase II trial of this agent has demonstrated promising results with a response rate of 37.5% and a median survival of 8.8 months with a mild toxicity profile for patients with metastatic pancreatic cancer. This study investigated the maximum tolerated dose of S-1 based on the frequency of dose-limiting toxicities (DLT) of S-1 with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Patients and Methods: Patients with locally advanced pancreatic cancer in whom adenocarcinoma had been confirmed histologically or cytologically were enrolled in this study. S-1 was administered orally in escalating doses from 50 mg/m2, which is reported to be equivalent to 200 mg/m2 intravenous 5-fluorouracil, to 80 mg/m2 bid in 10 mg/m2 increments on the day of irradiation (Monday through Friday) during radiotherapy. Radiation therapy was delivered through four fields as a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. DLT was defined as grade 4 hematological toxicity and grade 3 or 4 non-hematological toxicity during chemoradiotherapy. The maximum tolerated dose was defined when three or more patients in a cohort of six patients experienced DLT. Results: Twenty-one patients (50 mg/m2 3 patients; 60 mg/m2 5 patients; 70 mg/m2 6 patients; 80 mg/m2 7 patients) were enrolled in this trial between May 2004 and November 2005. At 70 mg/m2 S-1, two of six patients demonstrated DLT involving grade 3 nausea and vomiting and grade 3 hemorrhagic gastritis, while all patients at dose levels other than 70 mg/m2 did not demonstrate any sign of dose-limiting toxicity. Of all 21 patients enrolled, 4 (19.0%) showed a partial response. More than a 50% reduction in the serum level of carbohydrate antigen 19–9 was observed in 12 (75%) of 16 patients in whom the pretreatment level was 100 U/ml or greater. Conclusion: The recommended dose of S-1 with concurrent radiotherapy is 80 mg/m2. This regimen may offer an easy alternative to intravenous 5-fluorouracil, and may be a promising treatment for locally advanced pancreatic cancer. A multicenter phase II trial of this regimen in patients with locally advanced pancreatic cancer is now underway. No significant financial relationships to disclose.

Final analysis of a phase II study of Yale-modified FOLFIRINOX (mFOLFIRINOX) in metastatic pancreatic cancer (MPC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 395-395 ◽  
Author(s):  
Edward Samuel James ◽  
Xiangyu Cong ◽  
Xiaopan Yao ◽  
Carol Hahn ◽  
Kristin Kaley ◽  
...  
Keyword(s):  
Phase Ii ◽  
Historical Data ◽  
Locally Advanced ◽  
Final Analysis ◽  
Open Label ◽  
Peritoneal Disease ◽  
Full Dose ◽  
Entire Cohort ◽  
Ecog Ps

395 Background: Although FOLFIRINOX is superior to gemcitabine in MPC, the regimen is associated with significant toxicities (Conroy et al. N Engl J Med 2011;364:1817). In our prior retrospective analysis, efficacy was not compromised by dose attenuations of FOLFIRINOX (Gunturu et al. Med Oncol 2013;30:361). Based on this analysis, a prospective phase II open label study to evaluate the efficacy and tolerability of mFOLFIRINOX in pts with locally advanced (LAPC) and MPC was conducted. Herein, we report the final analysis of the toxicity in LAPC and MPC, and the efficacy in MPC. Methods: Previously untreated pts with MPC or LAPC received mFOLFIRINOX every two wks with 25% dose reductions of irinotecan & bolus 5FU until progression, unacceptable toxicity, or surgical resection. All pts received prophylactic pegfilgrastim. CAT scans were obtained every 4 cycles for response assessment by RECIST. Toxicities in the entire cohort, and response rate (RR) & pt characteristics in the MPC cohort were compared to historical data reported by Conroy. PFS was determined for MPC cohort. Results: 31 pts with LAPC and 43 pts with MPC with ECOG PS 0/1 were enrolled between 11/11 and 01/14. Characteristics of evaluable (37/43) MPC pts were: med age, 61 yrs (range 50-76); male, 21; ECOG PS 0, 17; med # metastatic sites, 2; peritoneal disease, 14; biliary stent, 9; med # of cycles 10 (range 4-31). Grade 3/4 toxicities in entire cohort were: vomiting & peripheral neuropathy, 2.7%; ALT elevated, thromboembolism and febrile neutropenia, 4.1%; anemia, 5.4%; diarrhea,16.2% (no grade 4 diarrhea reported); neutropenia & fatigue, 12.2%; thrombocytopenia, 9.5%. Neutropenia (p<0.0001), vomiting (p=0.0014), and fatigue (0.0194) were significantly decreased compared to historical data. RR in 37 pts with MPC was 35.1% (0 CR, 13 PR, 19 SD, 5 PD) and similar to historical data (36.9%; p 0.86). PFS in MPC pts was 6.11 mo with 95% CI (5.29, 8.31). Conclusions: mFOLFIRINOX with prophylactic pegfilgrastim in pts with MPC is associated with improved tolerability compared to full dose FOLFIRINOX, while RR and PFS in pts with MPC is similar to that reported by Conroy et all using full dose FOLFIRINOX. MPC pts are in follow-up for OS. Follow up for LAPC patients is ongoing. Clinical trial information: NCT01523457.

A phase II open-label study of cpi-613 in combination with modified (m)FOLFIRINOX in patients with locally advanced pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4176-TPS4176
Author(s):  
David Lawrence Bajor ◽  
AMR MOHAMED ◽  
J. Eva Selfridge ◽  
Erin E. Anderson ◽  
Jeffrey Hardacre ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer ◽  
Open Label ◽  
Borderline Resectable ◽  
Nccn Guidelines

TPS4176 Background: For patients with locally advanced pancreatic cancer, neoadjuvant trials are the preferred strategy. The goals of neoadjuvant treatment are to diminish the size of the primary tumor to allow for safe surgical resection and to limit the chance of developing metastatic disease. mFOLFIRINOX is the gold-standard for treatment in the adjuvant setting and an acceptable regimen in the neoadjuvant setting with many ongoing neoadjuvant trials using it as a chemotherapeutic backbone. CPI-613 (devimistat) is a small-molecule inhibitor of pyruvate dehydrogenase and alpha-ketogluterate dehydrogenase that has been studied in combination with mFOLFIRINOX in a phase I trial of patients with metastatic pancreas cancer and shown to be safe at the proposed phase II dose. Methods: This is a single-center, single-arm phase II trial for patients with locally advanced pancreatic cancer; defined as either borderline resectable or unresectable according to NCCN guidelines and interpreted by the primary investigator. Patients with metastatic disease are excluded. Patients will receive treatment with CPI-613 and mFOLFIRINOX per the table below. The primary endpoint is overall survival. Secondary endpoints are progression free survival and resection rate. At the time of submission this study has completed initial accrual with 37 patients enrolled. Clinical trial information: NCT03699319. [Table: see text]

A Critical Overview of Systematic Reviews of Chemotherapy for Advanced and Locally Advanced Pancreatic Cancer using both AMSTAR2 and ROBIS as Quality Assessment Tools

2020 ◽  
Vol 15 ◽  
Author(s):  
Amit Dang ◽  
Surendar Chidirala ◽  
Prashanth Veeranki ◽  
BN Vallish
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Systematic Reviews ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Risk Of Bias ◽  
Low Risk ◽  
Locally Advanced Pancreatic Cancer ◽  
Grade 3 ◽  
Critical Overview

Background: We performed a critical overview of published systematic reviews (SRs) of chemotherapy for advanced and locally advanced pancreatic cancer, and evaluated their quality using AMSTAR2 and ROBIS tools. Materials and Methods: PubMed and Cochrane Central Library were searched for SRs on 13th June 2020. SRs with metaanalysis which included only randomized controlled trials and that had assessed chemotherapy as one of the treatment arms were included. The outcome measures, which were looked into, were progression-free survival (PFS), overall survival (OS), and adverse events (AEs) of grade 3 or above. Two reviewers independently assessed all the SRs with both ROBIS and AMSTAR2. Results: Out of the 1,879 identified records, 26 SRs were included for the overview. Most SRs had concluded that gemcitabine-based combination regimes, prolonged OS and PFS, but increased the incidence of grade 3-4 toxicities, when compared to gemcitabine monotherapy, but survival benefits were not consistent when gemcitabine was combined with molecular targeted agents. As per ROBIS, 24/26 SRs had high risk of bias, with only 1/26 SR having low risk of bias. As per AMSTAR2, 25/26 SRs had critically low, and 1/26 SR had low, confidence in the results. The study which scored ‘low’ risk of bias in ROBIS scored ‘low confidence in results’ in AMSTAR2. The inter-rater reliability for scoring the overall confidence in the SRs with AMSTAR2 and the overall domain in ROBIS was substantial; ROBIS: kappa=0.785, SEM=0.207, p<0.001; AMSTAR2: kappa=0.649, SEM=0.323, p<0.001. Conclusion: Gemcitabine-based combination regimens can prolong OS and PFS but also worsen AEs when compared to gemcitabine monotherapy. The included SRs have an overall low methodological quality and high risk of bias as per AMSTAR2 and ROBIS respectively.

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