A randomized phase II and coagulation study of bevacizumab alone or with docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4556-4556 ◽  
Author(s):  
I. A. Astsaturov ◽  
N. J. Meropol ◽  
R. K. Alpaugh ◽  
J. D. Cheng ◽  
N. L. Lewis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Circulating Endothelial Cells ◽  
Randomized Phase Ii ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Coagulation Study ◽  
Previously Treated

4556 Background: Vascular endothelial growth factor (VEGF) is overexpressed in pancreatic cancer and interacts with coagulation to promote angiogenesis. We performed this randomized phase II study of bevacizumab (BEV) alone or with docetaxel (DOC) in patients (pts) with previously treated metastatic pancreatic adenocarcinoma to investigate their clinical activity and interaction with coagulation. Methods: Eligible pts had one prior gemcitabine regimen, PS 0–1, measurable disease, and no bleeding/thrombosis. BEV was given at 10 mg/kg IV Q 2 weeks alone (Arm A) or with DOC (Arm B) at 35 mg/m2 IV on days 1, 8, and 15 Q 28 days. CT scans were obtained every 2 cycles. The primary endpoint was progression-free survival (PFS), with secondary endpoints response rate and overall survival (OS). Peripheral blood was obtained for coagulation parameters, basic fibroblast growth factor (bFGF), VEGF, and circulating endothelial cells (CEC). A two-stage design with a target median PFS of =4 months in either arm and early stopping for futility was utilized. Results: Thirty pts (15 per arm) received 88 cycles of therapy (44 per arm, median 2, range <1–10). Pt characteristics: median age 61.5 (range 38–81), ECOG 0/1 (11/19). Seven pts in Arm A and 8 in Arm B had grade 3/4 events. Serious adverse events were 5 DVT/PE (3-Arm A; 2-Arm B) and 2 bowel perforations (1 per arm). Best reponse was 4 pts with stable disease in Arm A and 5 pts with stable disease and one unconfirmed PR in Arm B. Median PFS and OS were 43 and 181 days in Arm A and 45 and 123 days in Arm B (p=0.5 for PFS, p=0.8 for OS). The study was stopped after only 2/15 pts per arm had PFS of =4 months. In multivariate analysis, higher bFGF (HR=1.4, p=0.008) and thrombin/antithrombin complex (TAT) levels on treatment (HR=1.75, p<0.001) were associated with worse OS. D-dimer, tissue factor and TAT levels on d15 were associated with increased venous thrombosis and GI perforation (p=0.04). VEGF plasma levels and CEC at all time points were not associated with clinical outcomes. Conclusions: BEV alone or with DOC has minimal antitumor activity in gemcitabine-refractory pancreatic cancer. Increased plasma bFGF and coagulation markers during therapy predict for worse OS and increased perforation and thrombosis. [Table: see text]

Randomized phase II trial of panitumumab (P), erlotinib (E), and gemcitabine (G) versus erlotinib-gemcitabine in patients with untreated, metastatic pancreatic adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 238-238 ◽  
Author(s):  
G. P. Kim ◽  
N. R. Foster ◽  
M. Salim ◽  
P. J. Flynn ◽  
D. F. Moore ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Phase Ii ◽  
Survival Data ◽  
Grade 5 ◽  
Cancer Models ◽  
Randomized Phase Ii ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Acneiform Rash ◽  
Grade 3 ◽  
Ecog Ps

238 Background: Dual inhibition of the EGFR pathway using erlotinib and the monoclonal antibody panitumumab results in greater antitumor activity in preclinical pancreatic cancer models. A trial evaluating this approach was conducted. Methods: A safety analysis was initially performed with 6 patients at P 4 mg/kg every two weeks, E 100 mg daily, G 1000 mg/m2 weekly of a 28-day cycle. PGE was well tolerated with a grade 3 fatigue as only dose-limiting toxicity. Patients (pts) were then randomized to either PGE or GE alone. Eligibility included: no prior chemo, ECOG PS 0-1, bilirubin <2x UL, AST <2.5x UL. CT scans every 2 cycles. Results: 93 pts (46-GE; 47-PGE) were randomized from January to August, 2010. Median age 61 years and 65% male. ECOG PS 0 (51%) and PS 1 (49%). No significant differences in baseline characteristics observed between treatment arms. 81 pts evaluable for AEs; 37 (46%) had a maximum grade 3 (at least possibly related to treatment), and 12 (15%) maximum grade 4 or 5. Treatment arms similar with respect to the overall AEs with exception grade 1-3 acneiform rash, GE (65%) vs. PGE (85%). Commonly occurring grade 4 AEs (at least possibly related) consisted of thrombosis (3 pts) and thrombocytopenia (2 pts). Two grade 5 events occurred in PGE arm—duodenal hemorrhage (possibly related) and pancolitis with multisystem failure (unlikely). An additional PGE pt died 30 days off study (grade 5 CHF, possibly). 54 patients (67%; 31-GE, 23-PGE) ended treatment; 38 (70%) for disease progression (24-GE; 14-PGE). Other reasons for treatment discontinuation: AEs (9; 17%), pt refusal (4; 7%), death on study (2; 4%), other (1). In 81 pts with at least 1 cycle of chemotherapy, the median PFS for GE 2.0 months and 3.3 months for PGE. Accrual for the study was recently completed and overall and 6-month survival data will be presented. Conclusions: This study involved an initial run-in design to define tolerable doses of dual EGFR inhibitors, PGE, in pancreatic cancer patients. Although preliminary, the randomized phase II portion has been completed and differences between GE and PGE in terms of relevant clinical outcomes, PFS, are observed. No significant financial relationships to disclose.

5-fluorouracil, oxaliplatin and dasatinib (FOLFOX-D) for previously untreated metastatic pancreatic adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS517-TPS517
Author(s):  
Thomas J. George ◽  
Long H. Dang ◽  
Karen Colleen Daily ◽  
Jason Scott Starr ◽  
Hiral D. Parekh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Target Lesion ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Investigation Methods ◽  
Cancer Phenotype

TPS517 Background: Systemic chemotherapy for pancreatic adenocarcinoma improves survival and cancer related symptoms. Most targeted agents combined with gemcitabine have consistently failed to demonstrate clinical benefits. Src is overexpressed in pancreatic cancer and promotes an aggressive cancer phenotype. Dasatinib (D) is an oral multi-tyrosine kinase inhibitor (TKI) affecting tumor proliferation through inhibition of Src, Bcr-Abl, CKit and other pathways. Inhibition of Src is associated with biologic modifications favorably modifying the pancreatic cancer phenotype and has synergy with restoring inherent chemosensitivity. Src inhibition can also increase oxaliplatin activity and modulate Tcell responses. The addition of D to the well-established backbone of FOLFOX represents a multifaceted line of scientific investigation. Methods: This is a multicenter phase II trial to determine activity and toxicity of FOLFOX + D in previously untreated metastatic pancreatic adenocarcinoma. Eligible pts must have at least 1 measurable target lesion by RECIST, ECOG PS 0-2, normal QTc and adequate organ function. Pts received standard cycles of mFOLFOX6 repeated q14d with continuous D (150mg PO daily). Tumor assessments occur q8w. Endpoints included progression-free survival (primary; PFS), objective and biochemical response rates, clinical benefit rate, freedom from metastases, overall survival (OS), toxicity, and quality of life. Exploratory tissue, circulating tumor cell and serum analyses to identify predictors of response are planned, particularly in those demonstrating durable disease control or exceptional response. Sample size was based on a 50% improved median PFS from 4 (historical) to 6 months. NCT01652976. Results: Enrollment continues on this prospective phase II study with 38 of 42 evaluable patients. There are no unexpected toxicities noted thus far. Clinical trial information: NCT01652976. [Table: see text]

Phase II and Pharmacodynamic Study of the Farnesyltransferase Inhibitor R115777 as Initial Therapy in Patients With Metastatic Pancreatic Adenocarcinoma

2003 ◽  
Vol 21 (7) ◽  
pp. 1301-1306 ◽  
Author(s):  
Steven J. Cohen ◽  
Linus Ho ◽  
Sulabha Ranganathan ◽  
James L. Abbruzzese ◽  
R. Katherine Alpaugh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Mononuclear Cells ◽  
Single Agent ◽  
Clinical Activity ◽  
Peripheral Blood Mononuclear ◽  
Pancreatic Cell ◽  
Metastatic Pancreatic Adenocarcinoma ◽  
Ftase Activity

Purpose: R115777 is a selective nonpeptidomimetic inhibitor of farnesyltransferase (FTase), one of several enzymes responsible for posttranslational modification that is required for the function of p21ras and other proteins. Given that RAS mutations are nearly universal in pancreatic cancer and R115777 demonstrated preclinical activity against pancreatic cell lines and xenografts, this phase II study was undertaken to determine its clinical activity and effect on target proteins in patients with measurable metastatic pancreatic adenocarcinoma. Patients and Methods: Twenty patients who had not received prior therapy for metastatic disease were treated with 300 mg of R115777 orally every 12 hours for 21 of 28 days. Inhibition of FTase activity in peripheral-blood mononuclear cells was measured using a lamin B C-terminus peptide as substrate. Western blot analysis was performed to monitor farnesylation status of the chaperone protein HDJ-2. Results: No objective responses were seen. Median time to progression was 4.9 weeks, and median survival time was 19.7 weeks. The estimated 6-month survival rate was 25%, with no patients progression-free at 6 months. Grade 3/4 toxicities were liver enzyme elevation, anemia, neutropenia, thrombocytopenia, fatigue, nausea/vomiting, rash, and anorexia. FTase activity (mean ± SD) decreased by 49.8% ± 9.8% 4 hours after treatment on day 1 and 36.1% ± 24.8% before treatment on day 15. HDJ-2 farnesylation (mean ± SD) decreased by 33.4% ± 19.8% on day 15. Conclusion: Although treatment with R115777 resulted in partial inhibition of FTase activity in mononuclear cells, it did not exhibit single-agent antitumor activity in patients with previously untreated metastatic pancreatic cancer.

Sign in / Sign up

Export Citation Format

Share Document