Phase II Study of the Optimal Scheme of Administration of Pazopanib in Thyroid Carcinoma

Summary

The objective of this study is to determine the feasibility of pazopanib treatment interruption with reintroduction at progression in iodine refractory progressive Differentiated Thyroid Cancer (DTC) patients as compared to pazopanib continuous administration.

Timeline

Start

2013-03

Primary completion

2019-01

Completion

2019-01

Publications

• Background Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C; Endocrine Malignancies Disease Oriented Group; Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010 Oct;11(10):962-72. doi: 10.1016/S1470-2045(10)70203-5. Epub 2010 Sep 17.
• Background Altorki N, Lane ME, Bauer T, Lee PC, Guarino MJ, Pass H, Felip E, Peylan-Ramu N, Gurpide A, Grannis FW, Mitchell JD, Tachdjian S, Swann RS, Huff A, Roychowdhury DF, Reeves A, Ottesen LH, Yankelevitz DF. Phase II proof-of-concept study of pazopanib monotherapy in treatment-naive patients with stage I/II resectable non-small-cell lung cancer. J Clin Oncol. 2010 Jul 1;28(19):3131-7. doi: 10.1200/JCO.2009.23.9749. Epub 2010 Jun 1.
• Background Billemont B, Medioni J, Taillade L, Helley D, Meric JB, Rixe O, Oudard S. Blood glucose levels in patients with metastatic renal cell carcinoma treated with sunitinib. Br J Cancer. 2008 Nov 4;99(9):1380-2. doi: 10.1038/sj.bjc.6604709. Epub 2008 Oct 7.
• Background Borson-Chazot F, Bardet S, Bournaud C, Conte-Devolx B, Corone C, D'Herbomez M, Henry JF, Leenhardt L, Peix JL, Schlumberger M, Wemeau JL; Expert Group for French Recommendations for the Management of Differentiated Thyroid Carcinomas of Vesicular Origin; Baudin E, Berger N, Bernard MH, Calzada-Nocaudie M, Caron P, Catargi B, Chabrier G, Charrie A, Franc B, Hartl D, Helal B, Kerlan V, Kraimps JL, Leboulleux S, Le Clech G, Menegaux F, Orgiazzi J, Perie S, Raingeard I, Rodien P, Rohmer V, Sadoul JL, Schwartz C, Tenenbaum F, Toubert ME, Tramalloni J, Travagli JP, Vaudrey C. Guidelines for the management of differentiated thyroid carcinomas of vesicular origin. Ann Endocrinol (Paris). 2008 Dec;69(6):472-86. doi: 10.1016/j.ando.2008.10.002. No abstract available.
• Background Brose M. S., et al. Effect of BRAFV600E on response to sorafenib in advanced thyroid cancer patients. J Clin Oncol (meeting Abstracts) 27.15S (2009) : 6002.
• Background Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM, Bauman JE, Martins RG. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2010 Nov 1;16(21):5260-8. doi: 10.1158/1078-0432.CCR-10-0994. Epub 2010 Sep 16.
• Background de la Fouchardiere C, Droz JP. Targeted therapies and thyroid cancer: an update. Anticancer Drugs. 2011 Aug;22(7):688-99. doi: 10.1097/CAD.0b013e32834319c7.
• Background Fagin JA, Tuttle RM, Pfister DG. Harvesting the low-hanging fruit: kinase inhibitors for therapy of advanced medullary and nonmedullary thyroid cancer. J Clin Endocrinol Metab. 2010 Jun;95(6):2621-4. doi: 10.1210/jc.2010-0800. No abstract available.
• Background GSK Laboratories. Investigator's Brochure of pazopanib, version 09 dated 25 Jan. 2012.Ref Type: Unpublished Work
• Background Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K, Mandel SJ, Flaherty KT, Loevner LA, O'Dwyer PJ, Brose MS. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008 Oct 10;26(29):4714-9. doi: 10.1200/JCO.2008.16.3279. Epub 2008 Jun 9.
• Background Hutson TE, Davis ID, Machiels JP, De Souza PL, Rottey S, Hong BF, Epstein RJ, Baker KL, McCann L, Crofts T, Pandite L, Figlin RA. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010 Jan 20;28(3):475-80. doi: 10.1200/JCO.2008.21.6994. Epub 2009 Dec 14.
• Background Freedman LS. Tables of the number of patients required in clinical trials using the logrank test. Stat Med. 1982 Apr-Jun;1(2):121-9. doi: 10.1002/sim.4780010204.
• Background Jebreel A, England J, Bedford K, Murphy J, Karsai L, Atkin S. Vascular endothelial growth factor (VEGF), VEGF receptors expression and microvascular density in benign and malignant thyroid diseases. Int J Exp Pathol. 2007 Aug;88(4):271-7. doi: 10.1111/j.1365-2613.2007.00533.x.
• Background Iwamoto FM, Lamborn KR, Robins HI, Mehta MP, Chang SM, Butowski NA, Deangelis LM, Abrey LE, Zhang WT, Prados MD, Fine HA. Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02). Neuro Oncol. 2010 Aug;12(8):855-61. doi: 10.1093/neuonc/noq025. Epub 2010 Mar 3.
• Background Kaplan, E. L and P. Meier. Nonparametric estimation from incomplete observations. J Am Stat Assoc 53 (1958): 457-81.
• Background Kumar R, Knick VB, Rudolph SK, Johnson JH, Crosby RM, Crouthamel MC, Hopper TM, Miller CG, Harrington LE, Onori JA, Mullin RJ, Gilmer TM, Truesdale AT, Epperly AH, Boloor A, Stafford JA, Luttrell DK, Cheung M. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther. 2007 Jul;6(7):2012-21. doi: 10.1158/1535-7163.MCT-07-0193.
• Background Lan, K. K. G. and D. L. De Mets. Discrete sequential boundaries for clinical trials. Biometrika 70 (1983): 659-63
• Background Leboulleux, S., Bastholt, L., and Krause TM. Vandetanib in locally advanced or metastatic differentiated thyroid cancer (papillary or follicular; DTC): a randomized, double-blind phase II trial. International Thyroid Conference;Paris, France; [ Sept 11.16, 2009. Abstr 0C.023.]. 2010. Ref Type: Abstract
• Background Monk BJ, Mas Lopez L, Zarba JJ, Oaknin A, Tarpin C, Termrungruanglert W, Alber JA, Ding J, Stutts MW, Pandite LN. Phase II, open-label study of pazopanib or lapatinib monotherapy compared with pazopanib plus lapatinib combination therapy in patients with advanced and recurrent cervical cancer. J Clin Oncol. 2010 Aug 1;28(22):3562-9. doi: 10.1200/JCO.2009.26.9571. Epub 2010 Jul 6.
• Background Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol. 2008 May;21 Suppl 2(Suppl 2):S37-43. doi: 10.1038/modpathol.2008.10.
• Background Pacini F, Castagna MG, Brilli L, Pentheroudakis G; ESMO Guidelines Working Group. Differentiated thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009 May;20 Suppl 4:143-6. doi: 10.1093/annonc/mdp156. No abstract available.
• Background Prince HM, Honemann D, Spencer A, Rizzieri DA, Stadtmauer EA, Roberts AW, Bahlis N, Tricot G, Bell B, Demarini DJ, Benjamin Suttle A, Baker KL, Pandite LN. Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034). Blood. 2009 May 7;113(19):4819-20. doi: 10.1182/blood-2009-02-207209. No abstract available.
• Background Ravaud, A., et al. Sunitinib in patients with refractory advanced thyroid cancer: the THYSU phase II trial. J Clin Oncol (Meeting Abstracts) 26.15_suppl (2008): 6058.
• Background Ricarte-Filho JC, Ryder M, Chitale DA, Rivera M, Heguy A, Ladanyi M, Janakiraman M, Solit D, Knauf JA, Tuttle RM, Ghossein RA, Fagin JA. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res. 2009 Jun 1;69(11):4885-93. doi: 10.1158/0008-5472.CAN-09-0727.
• Background Schlumberger M. [Papillary and follicular thyroid carcinoma]. Ann Endocrinol (Paris). 2007 Jun;68(2-3):120-8. doi: 10.1016/j.ando.2007.04.004. Epub 2007 Jun 19. French.
• Background Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ; Motesanib Thyroid Cancer Study Group. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008 Jul 3;359(1):31-42. doi: 10.1056/NEJMoa075853.
• Background Slamon D,. et al. Pazopanib + Lapatinib is more active than Lapatinib alone : Updated results from a randomized study in patients with first-line ErbB2-positive advanced or metastatic breast cancer [ESMO abstract 139P]. Ann Oncol. 2008c ;19 (supp 8) : viii 64-65.
• Background Sleijfer, S., et al. Phase II study of pazopanib (GW786034) in patients (pts) with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043. ASCO Meeting Abstracts 25.18_suppl (2007): 10031.
• Background Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarba JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. doi: 10.1200/JCO.2009.23.9764. Epub 2010 Jan 25.
• Background Soh EY, Duh QY, Sobhi SA, Young DM, Epstein HD, Wong MG, Garcia YK, Min YD, Grossman RF, Siperstein AE, Clark OH. Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid. J Clin Endocrinol Metab. 1997 Nov;82(11):3741-7. doi: 10.1210/jcem.82.11.4340.
• Background Volante M, Rapa I, Gandhi M, Bussolati G, Giachino D, Papotti M, Nikiforov YE. RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact. J Clin Endocrinol Metab. 2009 Dec;94(12):4735-41. doi: 10.1210/jc.2009-1233. Epub 2009 Oct 16.
• de la Fouchardiere C, Godbert Y, Dalban C, Illouz F, Wassermann J, Do Cao C, Bardet S, Zerdoud S, Chougnet CN, Zalzali M, Benisvy D, Niccoli P, Digue L, Lamartina L, Schwartz P, Borson Chazot F, Gautier J, Perol D, Leboulleux S; PAZOTHYR investigators. Intermittent versus continuous administration of pazopanib in progressive radioiodine refractory thyroid carcinoma: Final results of the randomised, multicenter, open-label phase II trial PAZOTHYR. Eur J Cancer. 2021 Nov;157:153-164. doi: 10.1016/j.ejca.2021.07.029. Epub 2021 Sep 9.

Drugs

Indications