Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer

Investigational New Drugs

Volumn 33, Issue 4, 2015, Pages 977-984

  Reddy, S M ^a   Kopetz, S ^a   Morris, J ^a   Parikh, N ^a   Qiao, W ^a   Overman, M J ^a   Fogelman, D ^a   Shureiqi, I ^a   Jacobs, C ^a   Malik, Z ^b   Jimenez, C A ^a   Wolff, R A ^a   Abbruzzese, J L ^c   Gallick, G ^a   Eng, C ^a  

^a UNIVERSITY OF TEXAS   (United States)

^b Norton Cancer Institute   (United States)

^c DUKE CANCER INSTITUTE   (United States)

Author keywords

AZD0530; Colon cancer; Colorectal cancer; Phase 2; Saracatinib; Src inhibitor; Src kinase

Indexed keywords

SARACATINIB; 1,3 BENZODIOXOLE DERIVATIVE; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; QUINAZOLINE DERIVATIVE; VASCULOTROPIN A; VEGFA PROTEIN, HUMAN;

ADULT; AGED; ARTICLE; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER MORTALITY; CANCER PATIENT; CANCER SURVIVAL; CLINICAL ARTICLE; DEHYDRATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEMALE; HUMAN; HYPERTRANSAMINASEMIA; HYPOALBUMINEMIA; HYPOCALCEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; INTESTINE PERFORATION; LEUKOPENIA; LYMPHOCYTOPENIA; MALE; METASTATIC COLORECTAL CANCER; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; NAUSEA; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEINURIA; SURVIVAL TIME; THROMBOCYTOPENIA; ADENOCARCINOMA; ANTAGONISTS AND INHIBITORS; BLOOD; CLINICAL TRIAL; COLORECTAL NEOPLASMS; DISEASE FREE SURVIVAL; MIDDLE AGED; PATHOLOGY;

ADENOCARCINOMA; AGED; ANTINEOPLASTIC AGENTS; BENZODIOXOLES; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; MALE; MIDDLE AGED; PROTEIN KINASE INHIBITORS; QUINAZOLINES; SRC-FAMILY KINASES; VASCULAR ENDOTHELIAL GROWTH FACTOR A;

EID: 84952637658     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-015-0257-z     Document Type: Article

References (40)

1. Siegel R, Desantis C, Jemal A (2014) Colorectal cancer statistics, 2014. CA: Cancer J Clin 64(2):104-17
2. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol: Off J Am Soc Clin Oncol 22(2):229-37
3. Rothenberg ML, Cox JV, DeVore RF, Hainsworth JD, Pazdur R, Rivkin SE et al (1999) A multicenter, phase II trial of weekly irinotecan (CPT-11) in patients with previously treated colorectal carcinoma. Cancer 85(4):786-95
4. Viloria-Petit A, Crombet T, Jothy S, Hicklin D, Bohlen P, Schlaeppi JM et al (2001) Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: A role for altered tumor angiogenesis. Cancer Res 61(13):5090-101
5. Hecht JR, Mitchell E, Chidiac T, Scroggin C, Hagenstad C, Spigel D et al (2009) A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J Clin Oncol: Off J Am Soc Clin Oncol 27(5):672-80
6. Tol J, Koopman M, Cats A, Rodenburg CJ, Creemers GJ, Schrama JG et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360(6):563-72
7. Poindessous V, Ouaret D, El Ouadrani K, Battistella A, Megalophonos VF, Kamsu-Kom N et al (2011) EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies. Clin Cancer Res: Off J Am Assoc Cancer Res 17(20):6522-30
8. Penuel E, Martin GS (1999) Transformation by v-Src: Ras-MAPK and PI3K-mTOR mediate parallel pathways. Mol Biol Cell 10(6):1693-703
9. Xie G, Peng Z, Raufman JP (2012) Src-mediated aryl hydrocarbon and epidermal growth factor receptor cross talk stimulates colon cancer cell proliferation. Am J Physiol Gastrointest Liver Physiol 302(9):G1006-15
10. Niu G, Wright KL, Huang M, Song L, Haura E, Turkson J et al (2002) Constitutive Stat3 activity up-regulates VEGF expression and tumor angiogenesis. Oncogene 21(13):2000-8
11. Chen J, Elfiky A, Han M, Chen C, Saif MW (2014) The role of Src in colon cancer and its therapeutic implications. Clin Colorectal Cancer 13(1):5-13
12. Gray MJ, Zhang J, Ellis LM, Semenza GL, Evans DB, Watowich SS et al (2005) HIF-1alpha, STAT3, CBP/p300 and Ref-1/APE are components of a transcriptional complex that regulates Src-dependent hypoxia-induced expression of VEGF in pancreatic and prostate carcinomas. Oncogene 24(19):3110-20
13. Puls LN, Eadens M, Messersmith W (2011) Current status of SRC inhibitors in solid tumor malignancies. Oncologist 16(5):566-78
14. Cartwright CA, Meisler AI, Eckhart W (1990) Activation of the pp60c-src protein kinase is an early event in colonic carcinogenesis. Proc Natl Acad Sci U S A 87(2):558-62
15. Aligayer H, Boyd DD, Heiss MM, Abdalla EK, Curley SA, Gallick GE (2002) Activation of Src kinase in primary colorectal carcinoma: An indicator of poor clinical prognosis. Cancer 94(2):344-51
16. Talamonti MS, Roh MS, Curley SA, Gallick GE (1993) Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer. J Clin Invest 91(1):53-60
17. Green TP, Fennell M, Whittaker R, Curwen J, Jacobs V, Allen J et al (2009) Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530. Mol Oncol 3(3):248-61
18. Investigator's Brochure AZD0530 (2005) In: AstraZeneca Pharmaceuticals M, Cheshire, England
19. Hennequin L, Allen J, Costello GF et al (2005) The discovery of AZD0530: A novel, oral, highly selective and dual-specific inhibitor of the Src and Abl family kinases. Proc Am Assoc Cancer Res 46:A2537
20. Baselga J, Cervantes A, Martinelli E, Chirivella I, Hoekman K, Hurwitz HI et al (2010) Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumors. Clin Cancer Res: Off J Am Assoc Cancer Res 16(19):4876-83
21. Gangadhar TC, Clark JI, Karrison T, Gajewski TF (2013) Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma. Investig New Drugs 31(3):769-73
22. Mackay HJ, Au HJ, McWhirter E, Alcindor T, Jarvi A, MacAlpine K et al (2012) A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: A trial of the PMH phase II consortium. Investig New Drugs 30(3):1158-63
23. Fury MG, Baxi S, Shen R, Kelly KW, Lipson BL, Carlson D et al (2011) Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Anticancer Res 31(1):249-53
24. Lara PN Jr, Longmate J, Evans CP, Quinn DI, Twardowski P, Chatta G et al (2009) A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: A California Cancer Consortium study. Anti-Cancer Drugs 20(3):179-84
25. Gucalp A, Sparano JA, Caravelli J, Santamauro J, Patil S, Abbruzzi A et al (2011) Phase II trial of saracatinib (AZD0530), an oral SRC-inhibitor for the treatment of patients with hormone receptor-negative metastatic breast cancer. Clin Breast Cancer 11(5):306-11
26. Molina JR, Foster NR, Reungwetwattana T, Nelson GD, Grainger AV, Steen PD et al (2014) A phase II trial of the Src-kinase inhibitor saracatinib after four cycles of chemotherapy for patients with extensive stage small cell lung cancer: NCCTG trial N-0621. Lung Cancer 85(2):245-50
27. Messersmith WA NS, Arcaroli J et al. (2010) A phase II trial of saracatinib (AZD0530), an oral Src inhibitor, in previously treated metastatic paancreatic cancer. Journal of Clinical Oncology. Suppl: Abstr e14515
28. Laurie SA, Goss GD, Shepherd FA, Reaume MN, Nicholas G, Philip L et al (2014) A phase II trial of saracatinib, an inhibitor of src kinases, in previously-treated advanced non-small-cell lung cancer: the princess margaret hospital phase II consortium. Clin Lung Cancer 15(1):52-7
29. Renouf DJ, Moore MJ, Hedley D, Gill S, Jonker D, Chen E et al (2012) A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer. Investig New Drugs 30(2):779-86
30. McNeish IA, Ledermann JA, Webber L, James L, Kaye SB, Hall M et al (2014) A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer. Ann Oncol: Off J Eur Soc Med Oncol / ESMO 25(10):1988-95
31. Griffiths GJ, Koh MY, Brunton VG, Cawthorne C, Reeves NA, Greaves M et al (2004) Expression of kinase-defective mutants of c-Src in human metastatic colon cancer cells decreases Bcl-xL and increases oxaliplatin- and Fas-induced apoptosis. J Biol Chem 279(44):46113-21
32. Kopetz S, Lesslie DP, Dallas NA, Park SI, Johnson M, Parikh NU et al (2009) Synergistic activity of the SRC family kinase inhibitor dasatinib and oxaliplatin in colon carcinoma cells is mediated by oxidative stress. Cancer Res 69(9):3842-9
33. Dunn EF, Iida M, Myers RA, Campbell DA, Hintz KA, Armstrong EA et al (2011) Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab. Oncogene 30(5):561-74
34. Koppikar P, Choi SH, Egloff AM, Cai Q, Suzuki S, Freilino M et al (2008) Combined inhibition of c-Src and epidermal growth factor receptor abrogates growth and invasion of head and neck squamous cell carcinoma. Clin Cancer Res: Off J Am Assoc Cancer Res 14(13):4284-91
35. Ellis LM, Staley CA, Liu W, Fleming RY, Parikh NU, Bucana CD et al (1998) Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src. J Biol Chem 273(2):1052-7
36. Sharma MR, Wroblewski K, Polite BN, Knost JA, Wallace JA, Modi S et al (2012) Dasatinib in previously treated metastatic colorectal cancer: A phase II trial of the University of Chicago Phase II Consortium. Investig New Drugs 30(3):1211-5
37. Strickler JH, McCall S, Nixon AB, Brady JC, Pang H, Rushing C et al (2014) Phase I study of dasatinib in combination with capecitabine, oxaliplatin and bevacizumab followed by an expanded cohort in previously untreated metastatic colorectal cancer. Investig New Drugs 32(2):330-9
38. Lieu C, Wolff RA, Eng C et al. (2010) Phase 1B study of the Src inhibitor dasatinib with FOLFOX and cetuximab in metastatic colorectal cancer. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 28(15 suppl): Abstract 3536
39. Campone M, Bondarenko I, Brincat S, Hotko Y, Munster PN, Chmielowska E et al (2012) Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy. Ann Oncol: Off J Eur Soc Med Oncol / ESMO 23(3):610-7
40. Moy B, Neven P, Lebrun F, Bellet M, Xu B, Sarosiek T et al (2014) Bosutinib in combination with the aromatase inhibitor letrozole: A phase II trial in postmenopausal women evaluating first-line endocrine therapy in locally advanced or metastatic hormone receptor-positive/HER2-negative breast cancer. Oncologist 19(4):348-9