Phase i pharmacokinetic and pharmacodynamic study of the pan-PI3K/mTORC vascular targeted pro-drug SF1126 in patients with advanced solid tumours and B-cell malignancies

European Journal of Cancer

Volumn 48, Issue 18, 2012, Pages 3319-3327

  Mahadevan, D ^a   Chiorean, E G ^b   Harris, W B ^c   Von Hoff, D D ^d   Stejskal Barnett, A ^a   Qi, W ^a   Anthony, S P ^e   Younger, A E ^b   Rensvold, D M ^a   Cordova, F ^a   Shelton, C F ^e   Becker, M D ^e   Garlich, J R ^f   Durden, D L ^g   Ramanathan, R K ^d  

^a UNIVERSITY OF ARIZONA   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c EMORY UNIVERSITY   (United States)

^d Virginia G Piper Cancer Center/TGen   (United States)

^e Evergreen Hematology and Oncology   (United States)

^f SignalRx   (United States)

^g UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

B cell malignancies; Pharmacodynamics; Pharmacokinetics; PI3K mTORC pathway; Refractory solid tumours; SF1126

Indexed keywords

[1 (4 OXO 8 PHENYL 4H 1 BENZOPYRAN 2 YL)MORPHOLINIO]METHOXYSUCCINYLARGINYLGLYCYLASPARTYLSERINE ACETATE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RITUXIMAB;

ADULT; ADVANCED CANCER; AGED; ANEMIA; ANOREXIA; APOPTOSIS; AREA UNDER THE CURVE; ARTICLE; B CELL LYMPHOMA; BREAST CANCER; CHILL; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL ARTICLE; COLORECTAL CANCER; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG SAFETY; ENDOMETRIUM CANCER; ENZYME INHIBITION; FATIGUE; FEMALE; FEVER; GASTROINTESTINAL STROMAL TUMOR; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HUMAN; HYPOGLYCEMIA; HYPOKALEMIA; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; LYMPHOCYTE COUNT; MALE; MAXIMUM PERMISSIBLE DOSE; MAXIMUM PLASMA CONCENTRATION; MULTIPLE CYCLE TREATMENT; MUSCLE WEAKNESS; NAUSEA; NONHODGKIN LYMPHOMA; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROSTATE CANCER; PRURITUS; SARCOMA; SIDE EFFECT; SIGNAL TRANSDUCTION; URTICARIA; VOMITING;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CHROMONES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GASTROINTESTINAL DISEASES; HEMATOLOGIC DISEASES; HUMANS; HYPOKALEMIA; INFUSIONS, INTRAVENOUS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOMA, LARGE B-CELL, DIFFUSE; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; NEOPLASMS; OLIGOPEPTIDES; PHOSPHATIDYLINOSITOL 3-KINASES; PRODRUGS; PROTEIN KINASE INHIBITORS; PROTEINS; SALVAGE THERAPY; YOUNG ADULT;

EID: 84869505566     PISSN: 09598049     EISSN: 18790852     Source Type: Journal    
DOI: 10.1016/j.ejca.2012.06.027     Document Type: Article

References (29)

1. T.L. Yuan, and L.C. Cantley PI3K pathway alterations in cancer: variations on a theme Oncogene 27 2008 5497 5510
2. P. Liu, H. Cheng, and T.M. Roberts Targeting the phosphoinositide 3-kinase pathway in cancer Nat Rev Drug Discovery 8 2009 627 644
3. J.A. Engelman Targeting PI3K signaling in cancer: opportunities, challenges and limitations Nat Rev Cancer 9 2009 550 562
4. K.D. Courtney, R.B. Corcoran, and J.A. Engelman The PI3K pathway as drug target in human cancer J Clin Oncol 28 6 2010 1075 1083
5. T.O. Chan, S.E. Rittenhouse, and P.N. Tsichlis AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide- dependent phosphorylation Annu Rev Biochem 68 1999 965 1014 (Pubitemid 29449213)
6. H.C. Chen, and J.L. Guan Association of focal adhesion kinase with its potential substrate phosphatidylinositol 3-kinase Proc Natl Acad Sci U S A 91 21 1994 10148 10152
7. K. Izuhara, R.A. Feldman, and P. Greer Interleukin-4 induces association of the c-fes proto-oncogene product with phosphatidylinositol-3 kinase Blood 88 10 1996 3910 3918 (Pubitemid 26383115)
8. L.M. Karnitz, S.L. Sutor, and R.T. Abraham The Src-family kinase, Fyn, regulates the activation of phosphatidylinositol 3-kinase in an interleukin 2-responsive T cell line J Exp Med 179 6 1994 1799 1808 (Pubitemid 24155661)
9. N.R. Leslie, and C.P. Downes PTEN: the down side of PI 3-kinase signalling Cell Signal 14 4 2002 285 295 (Pubitemid 34164684)
10. V. Duronio, M.P. Scheid, and S. Ettinger Downstream signalling events regulated by phosphatidylinositol 3-kinase activity Cell Signal 10 4 1998 233 239 (Pubitemid 28205901)
11. E.S. Kandel, and N. Hay The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB Exp Cell Res 253 1 1999 210 229
12. B.H. Jiang, J.Z. Zheng, and M. Aoki Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells Proc Natl Acad Sci U S A 97 4 2000 1749 1753 (Pubitemid 30118514)
13. L. Hu, C. Zaloudek, and G.B. Mills In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002) Clin Cancer Res 6 3 2000 880 886 (Pubitemid 30159344)
14. J.D. Su, L.D. Mayo, and D.B. Donner PTEN and phosphatidylinositol 3′-kinase inhibitors up-regulate p53 and block tumor-induced angiogenesis: evidence for an effect on the tumor and endothelial compartment Cancer Res 63 13 2003 3585 3592 (Pubitemid 36793039)
15. J.R. Garlich, P. De, and N. Dey A vascular targeted pan phosphoinositide 3-kinase inhibitor prodrug, SF1126, with antitumor and antiangiogenic activity Cancer Res 68 1 2008 206 215 (Pubitemid 351380122)
16. P. Therasse, S.G. Arbuck, and E.A. Eisenhauer New guidelines to evaluate the response to treatment in solid tumors J Natl Cancer Inst 92 2000 205 216 (Pubitemid 30099779)
17. B.D. Cheson, B. Pfistner, and M.E. Juweid Revised response criteria for malignant lymphoma J Clin Oncol 25 2007 579 586 (Pubitemid 350002966)
18. M. Hallek, B.D. Cheson, and D. Catovsky Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic updating the National Cancer Institute Working Group 1996 Guidelines Blood 111 12 2008 5446 5456
19. M. Niedermeier, B.T. Hennessy, and Z.A. Knight Isoform-selective phosphoinositide 3′-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: A novel therapeutic approach Blood 113 22 2009 5549 5557
20. T.E. Witzig, and M. Gupta Signal transduction inhibitor therapy for lymphoma Hematology Am Soc Hematol Educ Program 2010 2010 265 270
21. B. Kloo, D. Nagel, and M. Pfeifer Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells Proc Natl Acad Sci U S A 108 1 2011 272 277
22. D.W. Bowles, and A. Jimeno New phosphatidylinositol 3-kinase inhibitors for cancer Expert Opin Investig Drugs 20 4 2011 507 518
23. I. Brana, P. LoRusso, and J. Besalga A Phase I dose-escalation study of the safety, pharmacokinetics (PK), and pharmacodynamics of XL765 (SAR245409), a PI3K/TORC1/TORC2 inhibitor administered orally to patients (pts) with advanced malignancies J Clin Oncol 28 2010 15s (suppl; abstr 3030)
24. A.J. Wagner, D.D. Von Hoff, and P.M. LoRusso A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors J Clin Oncol 27 2009 146s (suppl; abstr 3501)
25. G. Edelman, C. Bedell, and G. Shapiro Phase I dose-escalation study of XL147 (SAR245408), a PI3K inhibitor administered orally to patients (pts) with advanced malignancies J Clin Oncol 28 2010 15s (suppl; abstr 3004)
26. A. Jimeno, R.S. Herbst, and G.S. Falchook Final results from a Phase I, dose-escalation study of PX-866, an irreversible, pan-isoform inhibitor of PI3 kinase J Clin Oncol 28 2010 15s (suppl; abstr 3089)
27. J.C. Bendell, J. Rodon, and H.A. Burris Phase I, dose-escalation study of BKM120, an oral pan-class I PI3K inhibitor, in patients with advanced solid tumors J Clin Oncol 30 3 2012 282 290
28. B. Markman, J. Tabernero, and I. Krop Phase I safety, pharmacokinetic, and pharmacodynamics study of the oral phosphatidylinositol-3-kinase and mTOR inhibitor BGT226 in patients with advanced solid tumors Ann Oncol 2012 [Epub ahead of print] PMID:22357447
29. R.R. Furman, J.C. Byrd, and I. Flinn Interim results from a phase I study of CAL-101, a selective oral inhibitor of phosphatidylinositol 3-kinasep110d isoform, in patients with relapsed or refractory hematologic malignancies J Clin Oncol 28 2010 15s abstract 3032