Randomized, phase II, placebo-controlled, double-blind study with and without enzastaurin in combination with paclitaxel and carboplatin as first-line treatment followed by maintenance treatment in advanced ovarian cancer

Journal of Clinical Oncology

Volumn 31, Issue 25, 2013, Pages 3127-3132

  Vergote, Ignace B ^a   Amant, Frederic ^a   Chekerov, Radoslav ^b   Sehouli, Jalid ^b   Harter, Philipp ^c   Bauknecht, Thomas ^d   Mansouri, Kambiz ^d   Casado, Antonio ^e   Emerich, Janusz ^f   Myrand, Scott P ^g   Nguyen, Tuan S ^g   Shi, Peipei ^g  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c KLINIKEN ESSEN MITTE   (Germany)

^d LILLY DEUTSCHLAND GMBH   (Germany)

^e HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^f Provincial Specialist Hospital   (Poland)

^g ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBOPLATIN; ENZASTAURIN; HEMOGLOBIN; PACLITAXEL; PLACEBO; ANTINEOPLASTIC AGENT; INDOLE DERIVATIVE; PROTEIN KINASE C; PROTEIN KINASE C BETA;

ABDOMINAL PAIN; ADULT; ALOPECIA; ANTINEOPLASTIC ACTIVITY; ARTHRALGIA; ARTICLE; BLINDNESS; CANCER CHEMOTHERAPY; CANCER STAGING; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG HYPERSENSITIVITY; DRUG SAFETY; DYSGEUSIA; EDEMA; FATIGUE; FEMALE; FOLLOW UP; HUMAN; IMMUNOHISTOCHEMISTRY; LOADING DRUG DOSE; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA; OVARY CANCER; OVARY CARCINOMA; PERITONEAL EPITHELIAL CARCINOMA; PERITONEUM CANCER; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN DETERMINATION; RANDOMIZED CONTROLLED TRIAL; RISK ASSESSMENT; SENSORY NEUROPATHY; THROMBOCYTOPENIA; TRANSLATIONAL RESEARCH; TREATMENT RESPONSE; UTERINE TUBE CARCINOMA; VOMITING; AGED; CONTROLLED CLINICAL TRIAL; DRUG ANTAGONISM; MIDDLE AGED; MORTALITY; OVARY TUMOR;

ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARBOPLATIN; DOUBLE-BLIND METHOD; FEMALE; HUMANS; INDOLES; MIDDLE AGED; OVARIAN NEOPLASMS; PACLITAXEL; PROTEIN KINASE C;

EID: 84886518110     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2012.44.9116     Document Type: Article

References (29)

1. Ferlay J, Parkin DM, Steliarova-Foucher E: Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765-781, 2010.
2. Ozols RF: Challenges for chemotherapy in ovarian cancer. Ann Oncol 17:v181-v187, 2006 (suppl 5).
3. Stuart GC, Kitchener H, Bacon M, et al: 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: Report from the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer 21:750-755, 2011.
4. Ozols RF: Maintenance therapy in advanced ovarian cancer: Progression-free survival and clinical benefit. J Clin Oncol 21:2451-2453, 2003.
5. Markman M, Bundy BN, Alberts DS, et al: Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: An intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol 19:1001-1007, 2001.
6. Burger RA, Brady MF, Bookman MA, et al: Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol 28:5s, 2010 (suppl; abstr LBA1).
7. Perren TJ, Swart AM, Pfisterer J, et al: A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 365:2484-2496, 2011.
8. Gescher A: Analogs of staurosporine: Potential anticancer drugs? Gen Pharmacol 31:721-728, 1998.
9. Jarvis WD, Grant S: Protein kinase C targeting in antineoplastic treatment strategies. Invest New Drugs 17:227-240, 1999.
10. Parker PJ: Inhibition of protein kinase C: Do we, can we, and should we? Pharmacol Ther 82: 263-267, 1999.
11. Aeder SE, Martin PM, Soh JW, et al: PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways. Oncogene 23: 9062-9069, 2004.
12. Ma S, Rosen ST: Enzastaurin. Curr Opin Oncol 19:590-595, 2007.
13. Graff JR, McNulty AM, Hanna KR, et al: The protein kinase C beta-selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts. Cancer Res 65:7462-7469, 2005.
14. Civallero M, Cosenza M, Grisendi G, et al: Effects of enzastaurin, alone or in combination, on signaling pathway controlling growth and survival of B-cell lymphoma cell lines. Leuk Lymphoma 51:671- 679, 2010.
15. Hainsworth JD, Arrowsmith ER, McCleod M, et al: Randomized phase II study of R-CHOP plus enzastaurin versus R-CHOP in the first-line treatment of patients with intermediate and high-risk diffuse large B-cell lymphoma: Preliminary analysis. J Clin Oncol 29:508s, 2011 (suppl; abstr 8016).
16. Querfeld C, Kuzel TM, Kim YH, et al: Multicenter phase II trial of enzastaurin in patients with relapsed or refractory advanced cutaneous T-cell lymphoma. Leuk Lymphoma 52:1474-1480, 2011.
17. Carducci MA, Musib L, Kies MS, et al: Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J Clin Oncol 24: 4092-4099, 2006.
18. Herbst RS, Thornton DE, Kies MS, et al: Phase 1 study of LY317615, a protein kinase Cβ inhibitor. Proc Am Soc Clin Oncol 21:15s, 2002 (suppl; abstr 326).
19. Vergote I, Amant F, Oskay-Oezcelik G, et al: Carboplatin and paclitaxel in combination with oral enzastaurin in advanced ovarian or primary peritoneal cancer: Results from a safety lead-in study. Int J Gynecol Cancer 19:1505-1510, 2009.
20. Miller R, Siegmund D: Maximally selected chi square statistics. Biometrics 38:1011-1016, 1982.
21. Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors: European Organisation for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205-216, 2000.
22. Vergote I, Rustin GJ, Eisenhauer EA, et al: Re: New guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]-Gynecologic Cancer Intergroup. J Natl Cancer Inst 92:1534-1535, 2000.
23. MedDRA Maintenance and Support Services Organization. http://www.meddramsso.com/files-acrobat/messenger/Messenger-Mar-2010.pdf.
24. Richards DA, Kuefler PR, Becerra C, et al: Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: Results of a phase II, randomized, noncomparative study. Invest New Drugs 29:144-153, 2011.
25. Ghobrial IM, Munshi NC, Harris BN, et al: A phase I safety study of enzastaurin plus bortezomib in the treatment of relapsed or refractory multiple myeloma. Am J Hematol 86:573-578, 2011.
26. Kaplan EL, Meier P: Nonparametric estimation of incomplete observations. J Am Stat Assoc 53:457-481, 1958.
27. Cox DR: Regression models and life tables. J R Stat Soc B 34:187-220, 1972.
28. du Bois A, Reuss A, Pujade-Lauraine E, et al: Role of surgical outcome as a prognostic factor in advance epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials-By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer 115:1234-1244, 2009.
29. Usha L, Sill MW, Darcy KM, et al: A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol Oncol 121:455-461, 2011.