Supporting Research

CRLX101

Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle.
S. Eliasof, D. Lazarus, C.G. Peters, R.I. Case, R.O. Cole, J. Hwang, T. Schluep, J. Chao, J. Lin, Y. Yen, H. Han, D.T. Wiley, J.E. Zuckerman and M.E. Davis
PNAS 2013 Aug 26

Serial diffusion MRI to monitor and model treatment response of the targeted nanotherapy CRLX101.
Ng TS, Wert D, Sohi H, Procissi D, Colcher DM, Raubitschek AA, Jacobs RE.
Clin Cancer Res. 2013 Mar 26

First-in-human phase 1/2a trial of CRLX101, a cyclodextrin-containing polymer-camptothecin nanopharmaceutical in patients with advanced solid tumor malignancies.
Weiss GJ, Chao J, Neidhart JD, Ramanathan RK, Bassett D, Neidhart JA, Choi CH, Chow W, Chung V, Forman SJ, Garmey E, Hwang J, Kalinoski DL, Koczywas M, Longmate J, Melton RJ, Morgan R, Oliver J, Peterkin JJ, Ryan JL, Schluep T, Synold TW, Twardowski P, Davis ME, Yen Y.
Invest New Drugs. 2013 Feb 9

Preclinical to Clinical Development of the Novel Camptothecin nanopharmaceutical CRLX101
S. Svenson, M. Wolfgang, J. Hwang, J. Ryan and S. Eliasof
Journal of Controlled Release 2011; 153: 49

CRLX101 (formerly IT-101)–A Novel Nanopharmaceutical of Camptothecin in Clinical Development
C. Young, T. S. Schluep, H. Hwang and S. Eliasof
Curr Bioact Compd. 2011; 7(1): 8

Pharmacokinetics and Tumor Dynamics of the Nanoparticle IT-101 from PET Imaging and Tumor Histological Measurements
T. Schluep, J. Hwang, I. Hildebrandt, J. Czernin, C. Choi, Alabi, B. Mack and M. E. Davis
PNAS 2009; 106 (27) 11394

Design and development of IT-101, a Cyclodextrin-containing Polymer Conjugate of Camptothecin
M. E. Davis
Advanced Drug Delivery Reviews 2009; 61(13) 1189

Preclinical Results of Camptothecin-Polymer Conjugate (IT-101) in Multiple Human Lymphoma Xenograft Models
T. Numbenjapon, J. Wang, D. Colcher, T. Schluep, M. E. Davis, J. Duringer, L. Kretzner, Y. Yen, S. J. Forman and A. Raubitschek
Clinical Cancer Research 2009; 15 (13) 4366

α-Methylprednisolone Conjugated Cyclodextrin Polymer-based Nanoparticles for Rheumatoid Arthritis Therapy
J. Hwang, K. Rodgers, J. Oliver and T. Schluep
Int J Nanomedicine. 2008; 3(3): 359

Pharmacokinetics and Biodistribution of the Camptothecin–polymer Conjugate IT-101 in Rats and Tumor-bearing Mice
T. Schluep, J. Cheng, K. Khin and M. E. Davis
Cancer Chemother. Pharmacol. 2006; 57: 654

Preclinical Efficacy of the Camptothecin-Polymer Conjugate
IT-101 in Multiple Cancer Models
T. Schluep, J. Hwang, J. Cheng, J. Heidel, D. Bartlett, B.Hollister and M. E. Davis
Clinical Cancer Research 2006; 12(5) 1606

Temporal Targeting of Tumour cells and Neovasculature with a Nanoscale
Delivery System
S. Sengupta, D. Eavarone, I. Capila, G. Zhao, N. Watson, T. Kiziltepe and R. Sasisekharan
Nature 2005; 436: 568

Renal Cell Carcinoma

High-dose bevacizumab in the treatment of patients with advanced clear cell renal carcinoma: A phase II trial of the Sarah Cannon Oncology Research Consortium. J. Hainsworth, D. Shipley, J. Reeves, E. Arrowsmith, E. Barnes, D. Waterhouse
Clin Genitourin Cancer. 2013 Sep;11(3):283-289.e.1

Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Motzer RJ, Porta C, Vogelzang NJ, Sternberg CN, Szczylik C, Zolnierek J, Kollmannsberger C, Rha SY, Bjarnason GA, Melichar B, De Giorgi U, Grünwald V, Davis ID, Lee JL, Esteban E, Urbanowitz G, Cai C, Squires M, Marker M, Shi MM, Escudier B.
Lancet Oncol. 2014 Mar;15(3):286-96.

Phase 3 trial of everolimus for metastatic renal cell carcinoma : final results and analysis of prognostic factors. Motzer RJ1, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grünwald V, Thompson JA, Figlin RA, Hollaender N, Kay A, Ravaud A; RECORD‐1 Study Group.
Cancer. 2010 Sep 15;116(18):4256-65.

Relapsed Ovarian Cancer

Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Eric Pujade-Lauraine, Felix Hilpert, Beatrice Weber, Alexander Reuss, Andres Poveda, Gunnar Kristensen, Roberto Sorio, Ignace Vergote, Petronella Witteveen, Aristotelis Bamias, Deolinda Pereira, Pauline Wimberger, Ana Oaknin, Mansoor Raza Mirza, Philippe Follana, David Bollag, and Isabelle Ray-Coquard. Journal of Clinical Oncology 2014;32: 1-10.

Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: A Gynecologic Oncology Group study. Maurie Markman, John Blessing, Stephen C. Rubin, Joseph Connor, Parviz Hanjani, Steven Waggoner. Gynecologic Oncology 101 (2006) 436-440.

Neoadjuvant Rectal Cancer

Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. S. T. Martin, H. M. Heneghan and D. C. Winter. British Journal of Surgery 2012; 99: 918–928.

Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer. G. Klautke, P. Feyerherd, K. Ludwig, F. Prall, T. Foitzik and R. Fietkau. British Journal of Cancer (2005) 92: 1215-1220.

Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorourach, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer. Mehta, V., Cho, C., Ford, J., Jambalos, C., Poen, J., Koong, A., Lin, A., Bastidas, J., Young, H., Dunphy, E., Fisher, G. International Journal Radiation Oncology Biol. Phys. 55(1): 132-137.

Combined Modality Therapy of Rectal Cancer: Decreased Acute Toxicity With the Preoperative Approach. Bruce D. Minsky, Alfred M. Cohen, Nancy Kemeny, Warren E. Enker, David P. Kelsen, Bonnie Reichman, Leonard Saltz, Elin R. Sigurdson, and Joanne Frankel. Journal of Clinical Oncology 10(8): 1218-1224.

Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. Rolf Sauer, Heinz Becker, Werner Hohenberger, Claus Rödel, Christian Wittekind, Rainer Fietkau, Peter Martus, Jörg Tschmelitsch, Eva Hager, Clemens F. Hess, Johann-H. Karstens, Torsten Liersch, Heinz Schmidberger, and Rudolf Raab. The New England Journal of Medicine 351(17): 1731-1740.

Hypoxia Inducible Factor

Overcoming disappointing results with antiangiogenic therapy by targeting hypoxia. Rapisarda A and Melillo G (2012). Nat Rev Clin Oncol 9(7):378-90.

Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia. Conley SJ, Gheordunescu E, Kakarala P, Newman B, Korkaya H, Heath AN, Clouthier SG and Wicha MS (2012). Proc Natl Acad Sci USA 109(8):2784-9.

Multihistology, target-driven pilot trial of oral topotecan as an inhibitor of hypoxia-inducible factor-1α in advanced solid tumors. Kummar S, Raffeld M, Juwara L, Horneffer Y, Strassberger A, Allen D, Steinberg SM, Rapisarda A, Spencer SD, Figg WD, Chen X, Turkbey IB, Choyke P, Murgo AJ, Doroshow JH and Melillo G (2011). Clin Cancer Res 17(15):5123-31.

Potent preclinical impact of metronomic low-dose oral topotecan combined with the antiangiogenic drug pazopanib for the treatment of ovarian cancer. Hashimoto K, Man S, Xu P, Cruz-Munoz W, Tang T, Kumar R and Kerbel RS (2010). Mol Cancer Ther 9(4):996-1006.

Bridging the gap between cytotoxic and biologic therapy with metronomic topotecan and pazopanib in ovarian cancer. Merritt WM, Nick AM, Carroll AR, Lu C, Matsuo K, Dumble M, Jennings N, Zhang S, Lin YG, Spannuth WA, Kamat AA, Stone RL, Shahzad MM, Coleman RL, Kumar R and Sood AK (2010). Mol Cancer Ther 9(4):985-95.

Increased antitumor activity of bevacizumab in combination with hypoxia inducible factor-1 inhibition. Rapisarda A, Hollingshead M, Uranchimeg B, Bonomi CA, Borgel SD, Carter JP, Gehrs B, Raffeld M, Kinders RJ, Parchment R, Anver MR, Shoemaker RH and Melillo G (2009). Mol Cancer Ther 8(7):1867-77.

Targeting both HIF-1 and HIF-2 in human colon cancer cells improves tumor response to sunitinib treatment. Burkitt K, Chun SY, Dang DT and Dang LH (2009). Mol Cancer Ther 8(5):1148-56.

Camptothecin

Differential interactions of camptothecin lactone and carboxylate forms with human blood components. Mi Z and Burke TG (1994). Biochemistry 33(34):10325-36.

Modification of the hydroxy lactone ring of camptothecin: inhibition of mammalian topoisomerase I and biological activity. Hertzberg RP, Caranfa MJ, Holden KG, Jakas DR, Gallagher G, Mattern MR, Mong SM, Bartus JO, Johnson RK and Kingsbury WD (1989). J Med Chem 32(3):715-20.

Phase II study of camptothecin (NSC-100880) in the treatment of advanced gastrointestinal cancer. Moertel CG, Schutt AJ, Reitemeier RJ and Hahn RG (1972). Cancer Chemother Rep 56(1):95-101

 CRLX301

Development of docetaxel-loaded intravenous formulation, Nanoxel-PM™ using polymer-based delivery system. Sa-Won Lee, Min-Hyuk Yun, Seung Wei Jeong, Chang-Hoon In, Ji-Young Kim, Min-Hyo Seo, Chaul-Min Pai, Sun-Ok Kim.
Journal of Controlled Release 155 (2011) 262–271.

Cancer Biology

Tumor Heterogeneity and Personalized Medicine. Longo, D. The New England Journal of Medicine 366;10 (2012) 956-957.

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing. Marco Gerlinger, M.D., Andrew J. Rowan, B.Sc., Stuart Horswell, M.Math., James Larkin, M.D., Ph.D., David Endesfelder, Dip.Math., Eva Gronroos, Ph.D., Pierre Martinez, Ph.D., Nicholas Matthews, B.Sc., Aengus Stewart, M.Sc., Patrick Tarpey, Ph.D., Ignacio Varela, Ph.D., Benjamin Phillimore, B.Sc., Sharmin Begum, M.Sc., Neil Q. McDonald, Ph.D., Adam Butler, B.Sc., David Jones, M.Sc., Keiran Raine, M.Sc., Calli Latimer, B.Sc., Claudio R. Santos, Ph.D., Mahrokh Nohadani, H.N.C., Aron C. Eklund, Ph.D., Bradley Spencer-Dene, Ph.D.,
Graham Clark, B.Sc., Lisa Pickering, M.D., Ph.D., Gordon Stamp, M.D., Martin Gore, M.D., Ph.D., Zoltan Szallasi, M.D.,
Julian Downward, Ph.D., P. Andrew Futreal, Ph.D., and Charles Swanton, M.D., Ph.D. New England Journal of Medicine 366;10 (2012) 883-892.