Randomized phase II/III clinical trial of elpamotide for patients with advanced pancreatic cancer: PEGASUS-PC Study

Cancer Science

Volumn 106, Issue 7, 2015, Pages 883-890

  Yamaue, Hiroki ^a   Tsunoda, Takuya ^a   Tani, Masaji ^a   Miyazawa, Motoki ^a   Yamao, Kenji ^b   Mizuno, Nobumasa ^b   Okusaka, Takuji ^c   Ueno, Hideki ^c   Boku, Narikazu ^d   Fukutomi, Akira ^d   Ishii, Hiroshi ^e   Ohkawa, Shinichi ^f   Furukawa, Masayuki ^g   Maguchi, Hiroyuki ^h   Ikeda, Masafumi ⁱ   Togashi, Yosuke ^j   Nishio, Kazuto ^j   Ohashi, Yasuo ^k  

^a WAKAYAMA MEDICAL UNIVERSITY   (Japan)

^b AICHI CANCER CENTER HOSPITAL   (Japan)

^c NATIONAL CANCER CENTER HOSPITAL   (Japan)

^d SHIZUOKA CANCER CENTER   (Japan)

^e CANCER INSTITUTE HOSPITAL   (Japan)

^f KANAGAWA CANCER CENTER   (Japan)

^g NATIONAL KYUSHU CANCER CENTER   (Japan)

^h TEINE KEIJINKAI HOSPITAL   (Japan)

ⁱ NATIONAL CANCER CENTER HOSPITAL EAST   (Japan)

^j KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^k CHUO UNIVERSITY   (Japan)

more..

Author keywords

Advanced pancreatic cancer; Elpamotide; Immunotherapy; Peptide vaccine; Phase II III

Indexed keywords

ASPARTATE AMINOTRANSFERASE; ELPAMOTIDE; GEMCITABINE; PLACEBO; ANTINEOPLASTIC AGENT; ARGINYL-PHENYLALANYL-VALYL-PROLYL-ASPARTYL-GLYCYL-ASPARAGYL-ARGINYL-ISOLEUCINE; CANCER VACCINE; DEOXYCYTIDINE; PEPTIDE FRAGMENT; VASCULOTROPIN RECEPTOR 2;

ADULT; ADVANCED CANCER; AGED; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CANCER CONTROL; CANCER IMMUNOTHERAPY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EROSION; FEMALE; FEVER; HUMAN; INJECTION SITE REACTION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; OVERALL SURVIVAL; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SURVIVAL RATE; SURVIVAL TIME; TREATMENT OUTCOME; ULCER; ADENOCARCINOMA; ANALOGS AND DERIVATIVES; CARCINOMA, ADENOSQUAMOUS; CLINICAL TRIAL; KAPLAN MEIER METHOD; MIDDLE AGED; MORTALITY; PANCREATIC NEOPLASMS; PATHOLOGY;

ADENOCARCINOMA; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CANCER VACCINES; CARCINOMA, ADENOSQUAMOUS; DEOXYCYTIDINE; DOUBLE-BLIND METHOD; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; PANCREATIC NEOPLASMS; PEPTIDE FRAGMENTS; TREATMENT OUTCOME; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 84936985276     PISSN: 13479032     EISSN: 13497006     Source Type: Journal    
DOI: 10.1111/cas.12674     Document Type: Article

References (48)

1. Vital Statistics in Japan, tabulated by Center for Cancer Control and Information Services, National Cancer Center, Japan. [Webpage]. 2013/07/01 [cited 2013 September 19]; Available from URL: http://ganjoho.jp/pro/statistics/en/table_download.html
2. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin 2013; 63: 11-30.
3. Monitoring of Cancer Incidence in Japan - Survival 2003-2005 Report (Center for Cancer Control and Information Services, National Cancer Center, 2013) [Japanese]. [Webpage]. 2013/07/01 [cited 2013 September 20]. Available from URL: http://ganjoho.jp/pro/statistics/en/table_download.html
4. Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270-5.
5. Colucci G, Giuliani F, Gebbia V et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell'Italia Meridionale. Cancer 2002; 94: 902-10.
6. Colucci G, Labianca R, Di Costanzo F et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 2010; 28: 1645-51.
7. Cunningham D, Chau I, Stocken DD et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27: 5513-8.
8. Heinemann V, Quietzsch D, Gieseler F et al. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 2006; 24: 3946-52.
9. Philip PA, Benedetti J, Corless CL et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605-10.
10. Poplin E, Feng Y, Berlin J et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27: 3778-85.
11. Moore MJ, Goldstein D, Hamm J et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25: 1960-6.
12. Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-25.
13. Von Hoff DD, Ervin T, Arena FP et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-703.
14. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004; 25: 581-611.
15. Korc M. Pathways for aberrant angiogenesis in pancreatic cancer. Mol Cancer 2003; 2: 8.
16. Itakura J, Ishiwata T, Shen B, Kornmann M, Korc M. Concomitant over-expression of vascular endothelial growth factor and its receptors in pancreatic cancer. Int J Cancer 2000; 85: 27-34.
17. Masood R, Cai J, Zheng T, Smith DL, Hinton DR, Gill PS. Vascular endothelial growth factor (VEGF) is an autocrine growth factor for VEGF receptor-positive human tumors. Blood 2001; 98: 1904-13.
18. Karayiannakis AJ, Bolanaki H, Syrigos KN et al. Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett 2003; 194: 119-24.
19. Kuwahara K, Sasaki T, Kuwada Y, Murakami M, Yamasaki S, Chayama K. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinicopathologic parameters and patient survival. Pancreas 2003; 26: 344-9.
20. Luo J, Guo P, Matsuda K et al. Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo. Int J Cancer 2001; 92: 361-9.
21. Seo Y, Baba H, Fukuda T, Takashima M, Sugimachi K. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer 2000; 88: 2239-45.
22. Solorzano CC, Baker CH, Bruns CJ et al. Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother Radiopharm 2001; 16: 359-70.
23. Itakura J, Ishiwata T, Friess H et al. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clin Cancer Res 1997; 3: 1309-16.
24. von Marschall Z, Cramer T, Hocker M et al. De novo expression of vascular endothelial growth factor in human pancreatic cancer: evidence for an autocrine mitogenic loop. Gastroenterology 2000; 119: 1358-72.
25. Bruns CJ, Shrader M, Harbison MT et al. Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice. Int J Cancer 2002; 102: 101-8.
26. Buchler P, Reber HA, Ullrich A et al. Pancreatic cancer growth is inhibited by blockade of VEGF-RII. Surgery 2003; 134: 772-82.
27. Reck M, von Pawel J, Zatloukal P et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 2009; 27: 1227-34.
28. Fuchs CS, Marshall J, Mitchell E et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007; 25: 4779-86.
29. Giantonio BJ, Catalano PJ, Meropol NJ et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25: 1539-44.
30. Sobrero A, Ackland S, Clarke S et al. Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Oncology 2009; 77: 113-9.
31. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-42.
32. Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-50.
33. Wada S, Tsunoda T, Baba T et al. Rationale for antiangiogenic cancer therapy with vaccination using epitope peptides derived from human vascular endothelial growth factor receptor 2. Cancer Res 2005; 65: 4939-46.
34. Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411-22.
35. Wolchok JD, Hodi FS, Weber JS et al. Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann N Y Acad Sci 2013; 1291: 1-13.
36. Miyazawa M, Ohsawa R, Tsunoda T et al. Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancer. Cancer Sci 2010; 101: 433-9.
37. Burris HA 3rd, Moore MJ, Andersen J et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15: 2403-13.
38. Sakai K, Okamoto I, Takezawa K et al. A novel mass spectrometry-based assay for diagnosis of EML4-ALK-positive non-small cell lung cancer. J Thorac Oncol 2012; 7: 913-8.
39. Asahara S, Takeda K, Yamao K, Maguchi H, Yamaue H. Phase I/II clinical trial using HLA-A24-restricted peptide vaccine derived from KIF20A for patients with advanced pancreatic caner. J Transl Med 2013; 11: 291.
40. Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-4.
41. Karkkainen MJ, Petrova TV. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene 2000; 19: 5598-605.
42. Van Cutsem E, Rivera F, Berry S et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol 2009; 20: 1842-7.
43. Clark AJ, Butowski NA, Chang SM et al. Impact of bevacizumab chemotherapy on craniotomy wound healing. J Neurosurg 2011; 114: 1609-16.
44. Okines A, Puerto OD, Cunningham D et al. Surgery with curative-intent in patients treated with first-line chemotherapy plus bevacizumab for metastatic colorectal cancer First BEAT and the randomised phase-III NO16966 trial. Br J Cancer 2009; 101: 1033-8.
45. Ishigami S, Natsugoe S, Miyazono F et al. CD3 zeta expression of regional lymph node and peripheral blood lymphocytes in gastric cancer. Anticancer Res 2004; 24: 2123.
46. Klink M, Kielbik M, Nowak M, Bednarska K, Sulowska Z. JAK3, STAT3 and CD3-zeta signaling proteins status in regard to the lymphocytes function in patients with ovarian cancer. Immunol Invest 2012; 41: 382.
47. Hazama S, Nakamura Y, Takenouchi H et al. A pahse I study of combination vaccine treatment of five therapeutic epitope-peptides for metastatic colorectal cancer; safety, immunological response, and clinical outcome. J Transl Med 2014; 12: 63.
48. Kindler HL, Niedzwiecki D, Hollis D et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer; phase III trial of the Cancer and Leukemia Group B (CALGB80303). J Clin Oncol 2010; 28: 3617.