A phase II study of single-agent RO4929097, a gamma-secretase inhibitor of Notch signaling, in patients with recurrent platinum-resistant epithelial ovarian cancer: A study of the Princess Margaret, Chicago and California phase II consortia

Gynecologic Oncology

Volumn 137, Issue 2, 2015, Pages 216-222

  Diaz Padilla, Ivan ^a   Wilson, Michelle K ^a   Clarke, Blaise A ^b   Hirte, Hal W ^c   Welch, Stephen A ^d   Mackay, Helen J ^a   Biagi, Jim J ^e   Reedijk, Michael ^a   Weberpals, Johanne I ^f   Fleming, Gini F ^g   Wang, Lisa ^a   Liu, Geoffrey ^a   Zhou, Chen ^a   Blattler, Chantale ^a   Ivy, S Percy ^h   Oza, Amit M ^a  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c JURAVINSKI CANCER CENTRE   (Canada)

^d LONDON REGIONAL CANCER PROGRAM   (Canada)

^e Cancer Centre of Southeastern Ontario   (Canada)

^f UNIVERSITY OF OTTAWA   (Canada)

^g UNIVERSITY OF CHICAGO   (United States)

^h NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Gamma secretase inhibitor; Notch; Ovarian cancer; Phase II clinical trial; RO4929097

Indexed keywords

N (6,7 DIHYDRO 6 OXO 5H DIBENZ[B,D]AZEPIN 7 YL) 2,2 DIMETHYL N' (2,2,3,3,3 PENTAFLUOROPROPYL)PROPANEDIAMIDE; NOTCH RECEPTOR; 2,2-DIMETHYL-N-(6-OXO-6,7-DIHYDRO-5H-DIBENZO(B,D)AZEPIN-7-YL)-N'-(2,2,3,3,3-PENTAFLUOROPROPYL)MALONAMIDE; BENZAZEPINE DERIVATIVE; ENZYME INHIBITOR; SECRETASE; TUMOR MARKER;

ADULT; AGED; ANEMIA; ARTICLE; CANCER CHEMOTHERAPY; CHEMOTHERAPY INDUCED NAUSEA AND VOMITING; CLINICAL ARTICLE; DIARRHEA; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; HUMAN; HUMAN TISSUE; HYPERTRANSAMINASEMIA; HYPOPHOSPHATEMIA; IMMUNOHISTOCHEMISTRY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; OVARY CARCINOMA; PERITONEUM CANCER; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; QT PROLONGATION; TREATMENT OUTCOME; UTERINE TUBE CARCINOMA; ANTAGONISTS AND INHIBITORS; CANADA; CANCER STEM CELL; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DRUG EFFECTS; METABOLISM; MIDDLE AGED; NEOPLASMS, GLANDULAR AND EPITHELIAL; ORAL DRUG ADMINISTRATION; OVARIAN NEOPLASMS; PATHOLOGY; SIGNAL TRANSDUCTION; UNITED STATES; VERY ELDERLY;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; AMYLOID PRECURSOR PROTEIN SECRETASES; BENZAZEPINES; BIOMARKERS, TUMOR; CALIFORNIA; CHICAGO; DISEASE-FREE SURVIVAL; ENZYME INHIBITORS; FEMALE; HUMANS; MIDDLE AGED; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEOPLASTIC STEM CELLS; ONTARIO; OVARIAN NEOPLASMS; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EID: 84933279009     PISSN: 00908258     EISSN: 10956859     Source Type: Journal    
DOI: 10.1016/j.ygyno.2015.03.005     Document Type: Article

References (47)

1. Banerjee S, Kaye SB. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res 2013;19:961-8.
2. Reya T, Morrison SJ, Clarke MF, et al. Stemcells, cancer, and cancer stemcells. Nature 2001;414:105-11.
3. Wang JC, Dick JE. Cancer stem cells: lessons fromleukemia. Trends Cell Biol 2005;15: 494-501.
4. Alvero AB, Chen R, Fu HH, et al. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 2009;8:158-66.
5. Stewart JM, Shaw PA, Gedye C, et al. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc Natl Acad Sci U S A 2011;108:6468-73.
6. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea-a paradigm shift. Cancer Res 2006;66:1883-90 (discussion 1895-6).
7. Tomao F, Papa A, Rossi L, et al. Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach. J Exp Clin Cancer Res 2013;32:48.
8. Steg AD, Bevis KS, Katre AA, et al. Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res 2012;18:869-81.
9. McAuliffe SM, Morgan SL, Wyant GA, et al. Targeting Notch, a key pathway for ovarian cancer stemcells, sensitizes tumors to platinumtherapy. Proc Natl Acad Sci U S A 2012;109:E2939-48.
10. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011;474:609-15.
11. Jung SG, Kwon YD, Song JA, et al. Prognostic significance of Notch 3 gene expression in ovarian serous carcinoma. Cancer Sci 2010;101:1977-83.
12. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999;284:770-6.
13. Rangarajan A, Talora C, Okuyama R, et al. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J 2001;20:3427-36.
14. Fan X, Mikolaenko I, Elhassan I, et al. Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res 2004;64:7787-93.
15. Hu W, Liu T, Ivan C, et al. Notch3 pathway alterations in ovarian cancer. Cancer Res 2014;74:3282-93.
16. Rahman MT, Nakayama K, Rahman M, et al. Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer. Am J Clin Pathol 2012;138:535-44.
17. Olsauskas-Kuprys R, Zlobin A, Osipo C. Gamma secretase inhibitors of Notch signaling. Oncol Targets Ther 2013;6:943-55.
18. Shah MM, Zerlin M, Li BY, et al. The role of Notch and gamma-secretase inhibition in an ovarian cancer model. Anticancer Res 2013;33:801-8.
19. Luistro L, He W, Smith M, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res 2009;69:7672-80.
20. Tolcher AW, Messersmith WA, Mikulski SM, et al. Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol 2012.
21. Gounder MM, Schwartz GK. Moving forward one Notch at a time. J Clin Oncol 2012; 30:2291-3.
22. Malpica A, Deavers MT, Lu K, et al. Grading ovarian serous carcinoma using a twotier system. Am J Surg Pathol 2004;28:496-504.
23. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.
24. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer 2011;21:419-23.
25. Reedijk M, Odorcic S, Chang L, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associatedwith poor overall survival. Cancer Res 2005;65:8530-7.
26. Allred DC, Harvey JM, Berardo M, et al. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 1998;11:155-68.
27. Gordon AN, Tonda M, Sun S, et al. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 2004;95:1-8.
28. Ahmed N, Abubaker K, Findlay J, et al. Cancerous ovarian stem cells: obscure targets for therapy but relevant to chemoresistance. J Cell Biochem 2013;114:21-34.
29. Wintzell M, Lofstedt L, Johansson J, et al. Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell features and sensitivity to 3-bromopyruvate. Cancer Biol Ther 2012;13:1454-62.
30. Abubaker K, Latifi A, Luwor R, et al. Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden. Mol Cancer 2013;12:24.
31. Aster JC, Blacklow SC. Targeting the Notch pathway: twists and turns on the road to rational therapeutics. J Clin Oncol 2012;30:2418-20.
32. Krop I, Demuth T, Guthrie T, et al. Phase I pharmacologic and pharmacodynamic study of the gamma secretase (Notch) inhibitor MK-0752 in adult patients with advanced solid tumors. J Clin Oncol 2012;30:2307-13.
33. Diaz-Padilla I, Hirte H, Oza AM, et al. A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors. Invest New Drugs 2013;31:1182-91.
34. Gupta PB, Onder TT, Jiang G, et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 2009;138:645-59.
35. Shao H, Huang Q, Liu ZJ. Targeting Notch signaling for cancer therapeutic intervention. Adv Pharmacol 2012;65:191-234.
36. Vo K, Amarasinghe B, Washington K, et al. Targeting notch pathway enhances rapamycin antitumor activity in pancreas cancers through PTEN phosphorylation. Mol Cancer 2011;10:138.
37. Schott AF, Landis MD, Dontu G, et al. Preclinical and clinical studies of gamma secretase inhibitors with docetaxel on human breast tumors. Clin Cancer Res 2013;19:1512-24.
38. Groeneweg JW, DiGloria CM, Yuan J, et al. Inhibition of notch signaling in combination with Paclitaxel reduces platinum-resistant ovarian tumor growth. Front Oncol 2014;4:171.
39. Groeneweg JW, Foster R, Growdon WB, et al. Notch signaling in serous ovarian cancer. J Ovarian Res 2014;7:95.
40. Steg A, Katre A, Goodman B, et al. Targeting the Notch ligand JAGGED1 in both tumor cells and stroma in ovarian cancer. Clin Cancer Res 2011;17:5674-85.
41. Park JT, Chen X, Trope CG, et al. Notch3 overexpression is related to the recurrence of ovarian cancer and confers resistance to carboplatin. Am J Pathol 2010;177: 1087-94.
42. Alniaimi AN, Demorest-Hayes K, Alexander VM, et al. Increased notch1 expression is associated with poor overall survival in patients with ovarian cancer. Int J Gynecol Cancer 2015;25:208-13.
43. Phng LK, Gerhardt H. Angiogenesis: a team effort coordinated by notch. Dev Cell 2009;16:196-208.
44. Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther 2014;141:140-9.
45. Ridgway J, Zhang G, Wu Y, et al. Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 2006;444:1083-7.
46. Hu W, Lu C, Dong HH, et al. Biological roles of the Delta family Notch ligand Dll4 in tumor and endothelial cells in ovarian cancer. Cancer Res 2011;71:6030-9.
47. Jubb AM, Miller KD, Rugo HS, et al. Impact of exploratory biomarkers on the treatment effect of bevacizumab in metastatic breast cancer. Clin Cancer Res 2011;17: 372-81.