A phase I/II clinical trial in patients with locally advanced and/or metastatic pancreatic cancer using a combination of low dose chemotherapy and RAD 001

2009 ◽  
pp. 109-110
Author(s):  
M. Joka ◽  
M. Thomas ◽  
L. Decroix ◽  
C. Hosius ◽  
K. -W. Jauch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase I ◽  
Low Dose ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Low Dose Chemotherapy

Combination of antiangiogenic therapy using the mTOR inhibitor RAD001 (everolimus) and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer: Dose-finding study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 360-360
Author(s):  
Mareile Joka ◽  
Stefan Hubert Boeck ◽  
Christian Hosius ◽  
Laetitia Decroix ◽  
Christoph May ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Low Dose ◽  
Mtor Inhibitor ◽  
Antiangiogenic Therapy ◽  
Locally Advanced ◽  
Study Drug ◽  
Dose Finding ◽  
Metastatic Pancreatic Cancer ◽  
Low Dose Chemotherapy

360 Background: This was an open-label, multicenter two-arm combined phase I (dose finding, cohort 1-5)/II (dose expansion) study of continuous doses of RAD001 every 2nd day or every day in combination with escalating low dose gemcitabine in patients (pts) with locally advanced and/or metastatic pancreatic cancer. The primary objective was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). The secondary objectives were to characterize safety and tolerability and to evaluate preliminary efficacy (ORR). Methods: A total of 27 pts were enrolled in phase I. All of these were analyzed in the safety population and 23 pts in the MTD-determining population. In total, 21 pts completed the study. Results: The MTD was determined to be 500mg/m2/week gemcitabine and 5mg/d RAD001 (cohort 4, 7 pts treated). In total, 3 DLTs occured: hepatic toxicity and unknown DLT as worsed case assumption in cohort 5 and hepatic toxicity in cohort 4. Overall, 25 of 27 pts (92.59%) reported at least one AE. Thrombocytopenia was most frequent AE, followed by leukopenia and nausea. In the individual dose groups, thrombocytopenia was most common in cohorts 1, 2 and 5, leukopenia in cohort 3 and nausea in cohort 4. The majority of pts experienced AEs with suspected relation to study drug (81.48%), AEs leading to dose adjustments or temporary interruption (77.78%) or required concomitant medication (66.67%). A total of 11 pts (40.74%) experienced SAEs. Two pts died during the study (not related to study drug). 4 pts were dicontinued permanently due to 2 AEs and 2 SAEs. ORR was 13%. None of the pts reported complete response (CR), the progressive disease rate was 13%. The clinical benefit rate was 78.3%. Conclusions: The present study was prematurely terminated due to slow recruitment and the dose expansion phase (phase II) was not started. In phase I, the MTD was determined to be 500mg/m2/week Gemcitabine and 5mg/d RAD001. No new safety concerns were identified for combination of antiangiogenic therapy using the mTOR- inhibitor RAD001 (Everolimus) and low dose chemotherapy for locally advanced and/or metastatic pancreatic cancer.

scholarly journals Combination of antiangiogenic therapy using the mTOR-inhibitor everolimus and low-dose chemotherapy for locally advanced and/or metastatic pancreatic cancer

2014 ◽  
Vol 25 (9) ◽  
pp. 1095-1101 ◽  
Author(s):  
Mareile Joka ◽  
Stefan Boeck ◽  
Christoph J. Zech ◽  
Thomas Seufferlein ◽  
Goetz von Wichert ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Low Dose ◽  
Mtor Inhibitor ◽  
Antiangiogenic Therapy ◽  
Locally Advanced ◽  
Metastatic Pancreatic Cancer ◽  
Low Dose Chemotherapy

FOLFIRINOX in locally advanced or metastatic pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 313-313 ◽  
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.

The mitochondrial metabolism inhibitor CPI-613 in combination with mFOLFIRINOX for pancreatic adenocarcinoma.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 264-264
Author(s):  
Angela Tatiana Alistar ◽  
Rodwige Desnoyer ◽  
Ralph D'Agostino
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase I ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Stage Iv ◽  
Phase I Clinical Trial ◽  
Glutamine Metabolism ◽  
Metastatic Pancreatic Cancer

264 Background: Stage IV pancreatic cancer is a lethal disease with limited treatment options. Current standard practice is combination chemotherapy with FOLFIRINOX or Gemcitabine + Abraxane. Despite these two new treatment options, the response rate and survival are limited in stage IV pancreatic cancer. The glycolic and mitochondrial metabolisms are aberrant in pancreatic cancer and translate into chemo-resistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as chemotherapy. CPI -613 is a novel anti-mitochondrial developed by Cornerstone Pharmaceuticals. Methods: A phase I clinical trial with mFOLFIRINOX+ CPI-613 in never treated for stage IV pancreatic cancer patients was initiated. The goals of this phase 1trial are: (1) To determine the Maximum Tolerated Dose (MTD) of CPI-613, when used in combination with mFOLFIRINOX, in patients with metastatic pancreatic cancer, (2) To assess the safety of CPI-613/ mFOLFIRINOX combination in patients with metastatic pancreatic cancer, and (3) To obtain preliminary data on efficacy of treatment with CPI-613/ mFOLFIRINOX Results: The MTD for CPI 613 was identified at 500mg/m2. The treatment combination is feasible and well-tolerated. The combination treatment was not found to have higher toxicity than FOLFIRINOX alone. The objective response rate was 53.9 % which is higher than FOLFIRINOX alone (reported as 31.6%). One patient has a complete radiologic and clinical response and two other patients have near complete responses. Conclusions: The preliminary efficacy data of this phase I clinical trial will inform a multi-institutional randomized phase II study of FOLFIRINOX vs. m FOLFIRINOX+ CPI613 in the near future. Clinical trial information: NCT01835041.

Tolerability and safety of a replication-competent adenovirus-mediated double suicide gene therapy (Ad5-yCD/mutTK(SR39)rep-ADP) with chemotherapy in locally advanced pancreatic cancer: Phase 1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15761-e15761
Author(s):  
Jong-Chan Lee ◽  
Dong Woo Shin ◽  
Se Yeol Yang ◽  
Min Jae Kim ◽  
Jae Hyup Jung ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Gene Therapy ◽  
Phase I ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Suicide Gene ◽  
Evaluation Period ◽  
Double Suicide

e15761 Background: Up to 35% of pancreatic cancers are considered ‘locally advanced’ (LAPC) at the time of diagnosis. Replication-competent adenovirus-mediated double suicide gene therapy (Ad5-yCD/mutTK(SR39)rep-ADP) showed an anti-cancer effect in prostatic cancer patients in previous studies. We aimed to investigate tolerability and safety of Ad5-yCD/mutTK(SR39)rep-ADP in combination with gemcitabine in patients with LAPC. Methods: In this single-center, open label, dose-escalation phase I trial, we recruited adult patients (≥18 years) with newly diagnosed LAPC. Patients with histologically confirmed pancreatic ductal adenocarcinoma with good performance were enrolled. We injected Ad5-yCD/mutTK(SR39)rep-ADP into pancreatic mass with EUS-FNB needle in combination with oral 5-fluorocytosine 500mg qd, oral valgancyclovir 450mg qd, and standard gemcitabine (1000mg/m2, day 1-8-15 infusion every 4 weeks). In the three-stage dose-escalation scheme with traditional 3+3 design, the dose of Ad5-yCD/mutTK(SR39)rep-ADP in each cohort was 1x1011, 2x1011, and 1x1012 vp/mL, respectively. Every patient has been evaluated adenovirus-induced toxicity in 8 weeks and tumor response in 12 weeks. The primary aim is to establish the maximum tolerated dose (MTD) of Ad5-yCD/mutTK(SR39)rep-ADP, as assessed by dose-limiting toxicities (DLT). Results: From 2016 to 2018, we enrolled 11 patients and analyzed nine patients for the final cohort. Two were dropped out by withdrawal of consents. In the first evaluation period (8 weeks), any of patients did not experience dose-related serious adverse event. Only one patients of in 3rd cohort experienced transient grade II fever. In the second evaluation period (12 weeks), two patients showed partial response (PR) and seven showed stable disease (SD). Adenovirus DNA fragments disappeared in median 50 days (range 20 – 139). After the gemcitabine periods, five patients received 2nd-line chemotherapy with FOLFIRINOX, and overall survival was median 14.9 months (range 8.9 – 21.9). Conclusions: In this phase I trial, Ad5-yCD/mutTK(SR39)rep-ADP has been well-tolerated without dose-related severe adverse events, and no MTD reached in locally advanced pancreatic cancer. Phase II clinical trial is needed for evaluating clinical efficacy. Clinical trial information: NCT02894944.

NANT cancer vaccine an orchestration of immunogenic cell death by overcoming immune suppression and activating NK and T cell therapy in patients with third line or greater metastatic pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS463-TPS463 ◽  
Author(s):  
Tara Elisabeth Seery ◽  
John H. Lee ◽  
Leonard S. Sender ◽  
Frank R. Jones ◽  
Arvind Manohar Shinde ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Vaccine ◽  
Low Dose ◽  
Metastatic Pancreatic Cancer ◽  
Immune Recognition ◽  
Tumor Cell Death ◽  
Low Dose Chemotherapy

TPS463 Background: Pancreatic cancer has multiple mechanisms to prevent immune recognition that lead to the creation of an immune suppressive tumor microenvironment. We hypothesize that effective and sustained response against tumors requires a coordinated approach that: 1. reverses the immune-suppressive tumor microenvironment, 2. induces immunogenic tumor cell death and 3. reengages NK and T-cell tumor response against a 4. cascade of tumor antigens. To test this hypothesis, we developed the NANT Cancer Vaccine (NCV), which combines metronomic low-dose chemotherapy, radiotherapy and multifaceted immunotherapy. In proof-of-concept trials, the NCV was tested in 10 patients with 3rd-line or greater pancreatic cancer. These trials showed that the NCV could be safely administered in an outpatient setting, with AEs that were manageable by dose-reduction, and preliminary survival results that exceed the standard of care in this heavily-treated population. We believe these results warrant further research, and this abstract describes our newly-designed trial. Methods: A phase 1b, single-arm, open-label trial of the NANT Cancer Vaccine in patients with recurrent metastatic pancreatic cancer has been initiated. Treatment will occur in 3-week cycles of low-dose chemotherapy (aldoxorubicin, cyclophosphamide, oxaliplatin, nab-paclitaxel, 5-FU/L), antiangiogenic therapy (bevacizumab), SBRT, engineered allogeneic high affinity CD16 NK-92 cells (haNK), IL-15RαFc (N-803), adenoviral vector-based CEA vaccine (Ad-CEA), yeast vector-based RAS vaccine (Ye-RAS), and an IgG1 PD-L1 inhibitor, avelumab. The primary endpoint is incidence of treatment-related adverse events. Secondary endpoints include ORR, DCR, PFS, and OS. A maximum of 24 patients will be enrolled. Clinical trial information: NCT03586869.

GA CPI 613: A single arm, open-label phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel for patients with locally advanced or metastatic pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS459-TPS459
Author(s):  
Angela Tatiana Alistar ◽  
Bonny Morris ◽  
Lawrence Harrison ◽  
Kai Bickenbach ◽  
Nancy Ginder ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Locally Advanced ◽  
Glutamine Metabolism ◽  
Metastatic Pancreatic Cancer ◽  
Clinical Activity ◽  
First Line ◽  
Open Label ◽  
Effective Treatments

TPS459 Background: Pancreatic cancer is the third leading cause of cancer death in the USA. The most effective treatments for first-line metastatic pancreatic cancer are FOLFIRINOX and gemcitabine plus nab-paclitaxel, which provide a median overall survival of 11·1 months and 8·5 months with moderate toxicity. Safer and more effective treatments are needed. The glycolic and mitochondrial metabolism are aberrant in pancreatic cancer and translate into chemoresistance. Inhibition of glutamine metabolism can potentially synergize with therapies that increase intracellular reactive oxygen species such as Nab-Paclitaxel. CPI- 613 is a novel antimitocondrial developed by Rafael Pharmaceuticals that showed preclinical activity in pancreatic cancer cell lines as well as promising clinical activity in combination with modified FOLFIRINOX in patients with stage IV pancreatic cancer. Preclinical data suggests possible synergy of CPI- 613 with nab-paclitaxel. Methods: This is a single arm, open-label, nonblinded phase I study of CPI-613 in combination with gemcitabine and nab-paclitaxel in patients with locally advanced or metastatic pancreatic cancer. Key eligibility criteria include: histologically or cytologically documented and measurable locally advanced or metastatic pancreatic adenocarcinoma, ECOG performance status 0-2, first line treatment for both locally advanced or metastatic. CPI-613 will be infused intravenously with a starting dose of 500 mg/m2 followed by 125 mg/m2 nab-paclitaxel and 1,000 mg/m2 gemcitabine on day 1, 8, 15 of a 28-day cycle. The study is comprised of a two-stage dose-escalation schema to evaluate the MTD of CPI-613. At least six months of treatment is planned for patients who have a response. Primary endpoint of the study is MTD of CPI 613 when combined with gemcitabine and nab-paclitaxel and secondary endpoints of the study are treatment related adverse events, CR and PR. This study was initiated in February 2018 at Atlantic Health System and within first seven months of the study, 11 out of 24 planned patients have been enrolled. Clinical trial information: NCT03435289.

Phase II/III clinical trial with VEGFR2-epitope peptide and gemcitabine for patients with locally advanced, metastatic, or unresectable pancreatic cancer: Pegasus-PC study.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Hiroki Yamaue ◽  
Masaji Tani ◽  
Motoki Miyazawa ◽  
Kenji Yamao ◽  
Nobumasa Mizuno ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Phase I ◽  
Sample Size ◽  
Survival Time ◽  
Phase Ii ◽  
Locally Advanced ◽  
Type I ◽  
Unresectable Pancreatic Cancer ◽  
Epitope Peptide

223 Background: Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664). Methods: The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for 50%-60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group. Results: No statistically significant survival time prolongation was observed in OTS102 add-on group (p = 0.92). However, the three-month landmark analysis revealed significant interaction between the treatment and reports of indurations or ulcerations (p = 0.005) in add-on group, and if patients survived for over three months, grade 1-2 patients had better survival than grade 0 (1-year survival: 47%(23/49) and 22%(9/44), respectively) in add-on group. Conclusions: Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site indurations or ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies. Clinical trial information: UMIN000001664.

Sign in / Sign up

Export Citation Format

Share Document