Efficacy and Safety Assessment of Oral LBH589 in Adult Patients With Advanced Soft TIssue Sarcoma After Pre-treatment Failure

NCT01136499 | Completed Phase 2

• 2 other identifiers: ESTIM-LBH2009-011280-37
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess efficacy and safety of LBH589 - Panobinostat®, a potent HDACi, in patients with advanced STS who experiment disease progression after or during first-line chemotherapy. The rational is based on the observation of activity of deacetylase inhibitor (DACi) in several pre-clinical models of STS including Synovial sarcoma and Ewing sarcoma.

Conditions

Soft Tissue Sarcoma

Keywords

Sarcoma; Safety; Efficacy; PANOBINOSTAT

Outcome Measures

Primary Outcomes (1)

• 3 months non progression rate

  3 months

Secondary Outcomes (5)

• Progression-free survival (PFS)

  6 months after the end of treatment (18 months after the start of treatment)

• Time to progression (TTP)

  6 months after the end of treatment (18 months after the start of treatment)

• best objective response rate

  6 months after the end of treatment (18 months after the start of treatment)

• Safety profile based on incidence, intensity and type of adverse events

  6 months after the end of treatment (18 months after the start of treatment)

• Plasmatic rate of LBH589

  6 months after the end of treatment (18 months after the start of treatment)

Study Arms (1)

LBH PANOBINOSTAT

EXPERIMENTAL

40 mg 3 days per week

Drug: LBH589 (Panobinostat®)

Interventions

LBH589 (Panobinostat®) DRUG

40 mg MWF. 40 mg of LBH589, orally administered on Monday, Wednesday and Friday (MWF) on a weekly schedule, until tumor progression or unacceptable toxicity.

Also known as: panobinostat

LBH PANOBINOSTAT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically proven advanced metastatic or unresectable soft tissue sarcoma, excluding osteosarcoma.
• Prior treatment with a doxorubicin containing regimen whether in the adjuvant setting or for metastatic/advanced disease. If doxorubicin was given as adjuvant therapy patient may be included if relapse occurs within a year of adjuvant therapy. If relapse occurs more than one year after the completion of adjuvant therapy, the patient must have received one prior regimen for metastatic disease. Patient may have received one or more previous line of therapy. Patients with sex cord tumors may be included after prior treatment with a platinum containing regimen (pretreatment with a doxorubicin containing regimen is not required for this patients subgroup).
• Patient has at least one site of measurable nodal disease at baseline ≥ 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (MRI is allowed only if CT scan can not be performed).
• ECOG performance status (PS) ≤ 2.
• Adequate haematological, liver and renal function:
• Absolute Neutrophil Count (ANC) ≥ 1.5 G/L,
• Hemoglobin ≥ 9 g/dL,
• Platelets ≥ 100 G/L,
• Total calcium (corrected for serum albumin) ≥ lower limit of normal (LLN) or correctable with supplements,
• Magnesium ≥ LLN or correctable with supplements,
• Potassium ≥ LLN or correctable with supplements,
• Phosphorus ≥ LLN or correctable with supplements,
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5.0 x ULN if liver metastasis are present),
• Serum bilirubin ≤ 1.5 x ULN,

You may not qualify if:

• Prior treatment with any HDAC or HSP90 inhibitor drug.
• Unresolved toxicities (≥ Grade 1) from prior therapy that would, in the opinion of the investigator, compromise patient safety.
• Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• Left ventricular systolic function (LVEF) determined by MUGA scan or echocardiogram \< center normal value,
• Complete left bundle branch block,
• Obligate use of a cardiac pacemaker,
• Congenital long QT syndrome,
• History or presence of ventricular tachyarrhythmia,
• Presence of unstable atrial fibrillation (ventricular response \> 100bpm),
• Clinically significant resting bradycardia (\< 50 bpm),
• Mean corrected QT interval (QTcF - n ≥ 3) ≥ 450 msec on screening ECG,
• Right bundle branch block + left anterior hemiblock (bifasicular block),
• Angina pectoris ≤ 3 months prior to starting study drug,
• Acute myocardial infarction (MI) ≤ 3 months prior to starting study drug,

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (1)

Centre Léon Berard

Lyon, France

Location

Related Publications (60)

• Herman JG, Latif F, Weng Y, Lerman MI, Zbar B, Liu S, Samid D, Duan DS, Gnarra JR, Linehan WM, et al. Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9700-4. doi: 10.1073/pnas.91.21.9700.

  PMID: 7937876 BACKGROUND

• Szyf M. DNA methylation properties: consequences for pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):233-8. doi: 10.1016/0165-6147(94)90317-4.

  PMID: 7940985 BACKGROUND

• Herman JG, Merlo A, Mao L, Lapidus RG, Issa JP, Davidson NE, Sidransky D, Baylin SB. Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 1995 Oct 15;55(20):4525-30.

  PMID: 7553621 BACKGROUND

• Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995 Jul;1(7):686-92. doi: 10.1038/nm0795-686.

  PMID: 7585152 BACKGROUND

• Herman JG, Jen J, Merlo A, Baylin SB. Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. Cancer Res. 1996 Feb 15;56(4):722-7.

  PMID: 8631003 BACKGROUND

• Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, Markowitz S, Willson JK, Hamilton SR, Kinzler KW, Kane MF, Kolodner RD, Vogelstein B, Kunkel TA, Baylin SB. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6870-5. doi: 10.1073/pnas.95.12.6870.

  PMID: 9618505 BACKGROUND

• Cameron EE, Baylin SB, Herman JG. p15(INK4B) CpG island methylation in primary acute leukemia is heterogeneous and suggests density as a critical factor for transcriptional silencing. Blood. 1999 Oct 1;94(7):2445-51.

  PMID: 10498617 BACKGROUND

• Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci PG, Lazar MA. Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol. 1998 Dec;18(12):7185-91. doi: 10.1128/MCB.18.12.7185.

  PMID: 9819405 BACKGROUND

• Grignani F, De Matteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Grignani F, Lazar MA, Minucci S, Pelicci PG. Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature. 1998 Feb 19;391(6669):815-8. doi: 10.1038/35901.

  PMID: 9486655 BACKGROUND

• Lin RJ, Nagy L, Inoue S, Shao W, Miller WH Jr, Evans RM. Role of the histone deacetylase complex in acute promyelocytic leukaemia. Nature. 1998 Feb 19;391(6669):811-4. doi: 10.1038/35895.

  PMID: 9486654 BACKGROUND

• Redner RL, Wang J, Liu JM. Chromatin remodeling and leukemia: new therapeutic paradigms. Blood. 1999 Jul 15;94(2):417-28. No abstract available.

  PMID: 10397708 BACKGROUND

• Yoshida M, Nomura S, Beppu T. Effects of trichostatins on differentiation of murine erythroleukemia cells. Cancer Res. 1987 Jul 15;47(14):3688-91.

  PMID: 2439196 BACKGROUND

• Yoshida M, Beppu T. Reversible arrest of proliferation of rat 3Y1 fibroblasts in both the G1 and G2 phases by trichostatin A. Exp Cell Res. 1988 Jul;177(1):122-31. doi: 10.1016/0014-4827(88)90030-4.

  PMID: 3134246 BACKGROUND

• Itazaki H, Nagashima K, Sugita K, Yoshida H, Kawamura Y, Yasuda Y, Matsumoto K, Ishii K, Uotani N, Nakai H, et al. Isolation and structural elucidation of new cyclotetrapeptides, trapoxins A and B, having detransformation activities as antitumor agents. J Antibiot (Tokyo). 1990 Dec;43(12):1524-32. doi: 10.7164/antibiotics.43.1524.

  PMID: 2276972 BACKGROUND

• Sugita K, Koizumi K, Yoshida H. Morphological reversion of sis-transformed NIH3T3 cells by trichostatin A. Cancer Res. 1992 Jan 1;52(1):168-72.

  PMID: 1727377 BACKGROUND

• Hoshikawa Y, Kwon HJ, Yoshida M, Horinouchi S, Beppu T. Trichostatin A induces morphological changes and gelsolin expression by inhibiting histone deacetylase in human carcinoma cell lines. Exp Cell Res. 1994 Sep;214(1):189-97. doi: 10.1006/excr.1994.1248.

  PMID: 8082721 BACKGROUND

• Medina V, Edmonds B, Young GP, James R, Appleton S, Zalewski PD. Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway. Cancer Res. 1997 Sep 1;57(17):3697-707.

  PMID: 9288776 BACKGROUND

• Biggs JR, Kudlow JE, Kraft AS. The role of the transcription factor Sp1 in regulating the expression of the WAF1/CIP1 gene in U937 leukemic cells. J Biol Chem. 1996 Jan 12;271(2):901-6. doi: 10.1074/jbc.271.2.901.

  PMID: 8557703 BACKGROUND

• Nakano K, Mizuno T, Sowa Y, Orita T, Yoshino T, Okuyama Y, Fujita T, Ohtani-Fujita N, Matsukawa Y, Tokino T, Yamagishi H, Oka T, Nomura H, Sakai T. Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line. J Biol Chem. 1997 Aug 29;272(35):22199-206. doi: 10.1074/jbc.272.35.22199.

  PMID: 9268365 BACKGROUND

• Sowa Y, Orita T, Minamikawa S, Nakano K, Mizuno T, Nomura H, Sakai T. Histone deacetylase inhibitor activates the WAF1/Cip1 gene promoter through the Sp1 sites. Biochem Biophys Res Commun. 1997 Dec 8;241(1):142-50. doi: 10.1006/bbrc.1997.7786.

  PMID: 9405248 BACKGROUND

• Sambucetti LC, Fischer DD, Zabludoff S, Kwon PO, Chamberlin H, Trogani N, Xu H, Cohen D. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem. 1999 Dec 3;274(49):34940-7. doi: 10.1074/jbc.274.49.34940.

  PMID: 10574969 BACKGROUND

• Yu X, Guo ZS, Marcu MG, Neckers L, Nguyen DM, Chen GA, Schrump DS. Modulation of p53, ErbB1, ErbB2, and Raf-1 expression in lung cancer cells by depsipeptide FR901228. J Natl Cancer Inst. 2002 Apr 3;94(7):504-13. doi: 10.1093/jnci/94.7.504.

  PMID: 11929951 BACKGROUND

• Nimmanapalli R, Fuino L, Bali P, Gasparetto M, Glozak M, Tao J, Moscinski L, Smith C, Wu J, Jove R, Atadja P, Bhalla K. Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res. 2003 Aug 15;63(16):5126-35.

  PMID: 12941844 BACKGROUND

• Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005 Oct;5(10):761-72. doi: 10.1038/nrc1716.

  PMID: 16175177 BACKGROUND

• Blagosklonny MV, Trostel S, Kayastha G, Demidenko ZN, Vassilev LT, Romanova LY, Bates S, Fojo T. Depletion of mutant p53 and cytotoxicity of histone deacetylase inhibitors. Cancer Res. 2005 Aug 15;65(16):7386-92. doi: 10.1158/0008-5472.CAN-04-3433.

  PMID: 16103091 BACKGROUND

• Warrell RP Jr, He LZ, Richon V, Calleja E, Pandolfi PP. Therapeutic targeting of transcription in acute promyelocytic leukemia by use of an inhibitor of histone deacetylase. J Natl Cancer Inst. 1998 Nov 4;90(21):1621-5. doi: 10.1093/jnci/90.21.1621.

  PMID: 9811311 BACKGROUND

• O'Connor OA, Heaney ML, Schwartz L, Richardson S, Willim R, MacGregor-Cortelli B, Curly T, Moskowitz C, Portlock C, Horwitz S, Zelenetz AD, Frankel S, Richon V, Marks P, Kelly WK. Clinical experience with intravenous and oral formulations of the novel histone deacetylase inhibitor suberoylanilide hydroxamic acid in patients with advanced hematologic malignancies. J Clin Oncol. 2006 Jan 1;24(1):166-73. doi: 10.1200/JCO.2005.01.9679. Epub 2005 Dec 5.

  PMID: 16330674 BACKGROUND

• Saito A, Yamashita T, Mariko Y, Nosaka Y, Tsuchiya K, Ando T, Suzuki T, Tsuruo T, Nakanishi O. A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4592-7. doi: 10.1073/pnas.96.8.4592.

  PMID: 10200307 BACKGROUND

• Piekarz RL, Robey R, Sandor V, Bakke S, Wilson WH, Dahmoush L, Kingma DM, Turner ML, Altemus R, Bates SE. Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report. Blood. 2001 Nov 1;98(9):2865-8. doi: 10.1182/blood.v98.9.2865.

  PMID: 11675364 BACKGROUND

• Parker C, Molife R, Karavasilis V, Reid A, Patterson SG, Riggs C et al. Romidepsin (FK228), a histone deacetylase inhibitor: Final results of a phase II study in metastatic hormone refractory prostate cancer (HRPC). J Clin Oncol (Meeting Abstracts) 2007;25:15507.

  BACKGROUND

• Rathkopf, D. E., Wong, B. Y., Ross, R. W., George, D. J., Picus, J., Sawyers, C. L., Chen, Y., Tanaka, E., Yang, W., Culver, K. W., and Scher, H. I. A phase I dose escalation study of oral panobinostat (LBH589) alone and in combination with IV docetaxel (Doc) and oral prednisone in castration-resistant prostate cancer (CRPC). 2008 Genitourinary Cancer Sympsium , abst. 171. 2008.

  BACKGROUND

• Clark MA, Fisher C, Judson I, Thomas JM. Soft-tissue sarcomas in adults. N Engl J Med. 2005 Aug 18;353(7):701-11. doi: 10.1056/NEJMra041866. No abstract available.

  PMID: 16107623 BACKGROUND

• Helman LJ, Meltzer P. Mechanisms of sarcoma development. Nat Rev Cancer. 2003 Sep;3(9):685-94. doi: 10.1038/nrc1168.

  PMID: 12951587 BACKGROUND

• Coindre JM, Terrier P, Bui NB, Bonichon F, Collin F, Le Doussal V, Mandard AM, Vilain MO, Jacquemier J, Duplay H, Sastre X, Barlier C, Henry-Amar M, Mace-Lesech J, Contesso G. Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol. 1996 Mar;14(3):869-77. doi: 10.1200/JCO.1996.14.3.869.

  PMID: 8622035 BACKGROUND

• Guillou L, Coindre JM, Bonichon F, Nguyen BB, Terrier P, Collin F, Vilain MO, Mandard AM, Le Doussal V, Leroux A, Jacquemier J, Duplay H, Sastre-Garau X, Costa J. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol. 1997 Jan;15(1):350-62. doi: 10.1200/JCO.1997.15.1.350.

  PMID: 8996162 BACKGROUND

• Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon F, N'Guyen Bui B. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001 May 15;91(10):1914-26. doi: 10.1002/1097-0142(20010515)91:103.0.co;2-3.

  PMID: 11346874 BACKGROUND

• Jebsen NL, Trovik CS, Bauer HC, Rydholm A, Monge OR, Hall KS, Alvegard T, Bruland OS. Radiotherapy to improve local control regardless of surgical margin and malignancy grade in extremity and trunk wall soft tissue sarcoma: a Scandinavian sarcoma group study. Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1196-203. doi: 10.1016/j.ijrobp.2007.11.023. Epub 2008 Jan 22.

  PMID: 18207661 BACKGROUND

• Adjuvant chemotherapy for localised resectable soft-tissue sarcoma of adults: meta-analysis of individual data. Sarcoma Meta-analysis Collaboration. Lancet. 1997 Dec 6;350(9092):1647-54.

  PMID: 9400508 BACKGROUND

• Woll PJ, Van GM, Hohenberger P, Le CA, Gronchi A, Hoekstra HJ et al. Adjuvant chemotherapy (CT) with doxorubicin and ifosfamide in resected soft tissue sarcoma (STS): Interim analysis of a randomised phase III trial. ASCO Meeting Abstracts 2007;25:10008.

  BACKGROUND

• Edmonson JH, Ryan LM, Blum RH, Brooks JS, Shiraki M, Frytak S, Parkinson DR. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol. 1993 Jul;11(7):1269-75. doi: 10.1200/JCO.1993.11.7.1269.

  PMID: 8315424 BACKGROUND

• Santoro A, Tursz T, Mouridsen H, Verweij J, Steward W, Somers R, Buesa J, Casali P, Spooner D, Rankin E, et al. Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1995 Jul;13(7):1537-45. doi: 10.1200/JCO.1995.13.7.1537.

  PMID: 7602342 BACKGROUND

• Prince HM, George DJ, Johnstone R, Williams-Truax R, Atadja P, Zhao C et al. LBH589, a novel histone deacetylase inhibitor (HDACi), treatment of patients with cutaneous T-cell lymphoma (CTCL). Changes in skin gene expression profiles related to clinical response following therapy. J Clin Oncol (Meeting Abstracts) 2006;24:7501.

  BACKGROUND

• Beck J, Fischer T, George D, Huber C, Calvo E, Atadja P et al. Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of ORAL LBH589B: A novel histone deacetylase (HDAC) inhibitor. J Clin Oncol (Meeting Abstracts) 2005;23:3148.

  BACKGROUND

• Beck J, Fischer T, Rowinsky E, Huber C, Mita M, Atadja P et al. Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of LBH589A: A novel histone deacetylase inhibitor. J Clin Oncol (Meeting Abstracts) 2004;22:3025.

  BACKGROUND

• Le Cesne A, Judson I, Crowther D, Rodenhuis S, Keizer HJ, Van Hoesel Q, Blay JY, Frisch J, Van Glabbeke M, Hermans C, Van Oosterom A, Tursz T, Verweij J. Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 2000 Jul;18(14):2676-84. doi: 10.1200/JCO.2000.18.14.2676.

  PMID: 10894866 BACKGROUND

• Garcia-Carbonero R, Supko JG, Manola J, Seiden MV, Harmon D, Ryan DP, Quigley MT, Merriam P, Canniff J, Goss G, Matulonis U, Maki RG, Lopez T, Puchalski TA, Sancho MA, Gomez J, Guzman C, Jimeno J, Demetri GD. Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy. J Clin Oncol. 2004 Apr 15;22(8):1480-90. doi: 10.1200/JCO.2004.02.098.

  PMID: 15084621 BACKGROUND

• Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, Lorigan P, Rodenhuis S, Ray-Coquard I, Bonvalot S, Collin F, Jimeno J, Di Paola E, Van Glabbeke M, Nielsen OS. Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005 Jan 20;23(3):576-84. doi: 10.1200/JCO.2005.01.180.

  PMID: 15659504 BACKGROUND

• Bay JO, Ray-Coquard I, Fayette J, Leyvraz S, Cherix S, Piperno-Neumann S, Chevreau C, Isambert N, Brain E, Emile G, Le Cesne A, Cioffi A, Kwiatkowski F, Coindre JM, Bui NB, Peyrade F, Penel N, Blay JY; Groupe Sarcome Francais. Docetaxel and gemcitabine combination in 133 advanced soft-tissue sarcomas: a retrospective analysis. Int J Cancer. 2006 Aug 1;119(3):706-11. doi: 10.1002/ijc.21867.

  PMID: 16496406 BACKGROUND

• Hensley ML, Maki R, Venkatraman E, Geller G, Lovegren M, Aghajanian C, Sabbatini P, Tong W, Barakat R, Spriggs DR. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol. 2002 Jun 15;20(12):2824-31. doi: 10.1200/JCO.2002.11.050.

  PMID: 12065559 BACKGROUND

• Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006 Sep;5(9):769-84. doi: 10.1038/nrd2133.

  PMID: 16955068 BACKGROUND

• Ito T, Ouchida M, Ito S, Jitsumori Y, Morimoto Y, Ozaki T, Kawai A, Inoue H, Shimizu K. SYT, a partner of SYT-SSX oncoprotein in synovial sarcomas, interacts with mSin3A, a component of histone deacetylase complex. Lab Invest. 2004 Nov;84(11):1484-90. doi: 10.1038/labinvest.3700174.

  PMID: 15467731 BACKGROUND

• Wunder JS, Nielsen TO, Maki RG, O'Sullivan B, Alman BA. Opportunities for improving the therapeutic ratio for patients with sarcoma. Lancet Oncol. 2007 Jun;8(6):513-24. doi: 10.1016/S1470-2045(07)70169-9.

  PMID: 17540303 BACKGROUND

• Kutko MC, Glick RD, Butler LM, Coffey DC, Rifkind RA, Marks PA, Richon VM, LaQuaglia MP. Histone deacetylase inhibitors induce growth suppression and cell death in human rhabdomyosarcoma in vitro. Clin Cancer Res. 2003 Nov 15;9(15):5749-55.

  PMID: 14654560 BACKGROUND

• Sakimura R, Tanaka K, Nakatani F, Matsunobu T, Li X, Hanada M, Okada T, Nakamura T, Matsumoto Y, Iwamoto Y. Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors. Int J Cancer. 2005 Sep 20;116(5):784-92. doi: 10.1002/ijc.21069.

  PMID: 15849726 BACKGROUND

• Prince HM, George D, Patnaik A, Mita M, Dugan M, Butterfoss D et al. Phase I study of oral LBH589, a novel deacetylase (DAC) inhibitor in advanced solid tumors and non-hodgkin's lymphoma. J Clin Oncol (Meeting Abstracts) 2007;25:3500. 66. A'Hern RP. Sample

  BACKGROUND

• A'Hern RP. Sample size tables for exact single-stage phase II designs. Stat Med. 2001 Mar 30;20(6):859-66. doi: 10.1002/sim.721.

  PMID: 11252008 BACKGROUND

• Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.

  BACKGROUND

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

• van Maldegem AM, Bovee JV, Gelderblom H. Panobinostat-A Potential Treatment for Metastasized Ewing Sarcoma? A Case Report. Pediatr Blood Cancer. 2016 Oct;63(10):1840-3. doi: 10.1002/pbc.26077. Epub 2016 Jun 1.

  PMID: 27245095 DERIVED

• Cassier PA, Lefranc A, Amela EY, Chevreau C, Bui BN, Lecesne A, Ray-Coquard I, Chabaud S, Penel N, Berge Y, Domont J, Italiano A, Duffaud F, Cadore AC, Polivka V, Blay JY. A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group. Br J Cancer. 2013 Aug 20;109(4):909-14. doi: 10.1038/bjc.2013.442. Epub 2013 Aug 6.

  PMID: 23922114 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• BLAY PR Jean-Yves

  Centre Léon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2010
• First Posted: June 3, 2010
• Study Start: January 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2013
• Last Updated: March 6, 2013

Record last verified: 2013-02

Locations

FR (1)