ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head & neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.

开始日期2007-06-01

申办/合作机构

Sigma Tau I.f.r S.p.a.

100 项与 Namitecan 相关的临床结果

登录后查看更多信息

100 项与 Namitecan 相关的转化医学

登录后查看更多信息

100 项与 Namitecan 相关的专利（医药）

登录后查看更多信息

项与 Namitecan 相关的文献（医药）

2015-07-01·British Journal of Clinical Pharmacology2区 · 医学

Integrative population pharmacokinetic and pharmacodynamic dose finding approach of the new camptothecin compound namitecan (ST1968)

2区 · 医学

Article

作者: Pace, S. ; Gallerani, E. ; Joerger, M. ; Barbieri, P. ; Delmonte, A. ; Gianni, L. ; Sessa, C. ; Hess, D. ; Cresta, S. ; Fasolo, A.

AimsNamitecan is a new camptothecan compound undergoing early clinical development. This study was initiated to build an integrated pharmacokinetic (PK) and pharmacodynamic (PD) population model of namitecan to guide future clinical development.MethodsPlasma concentration–time data, neutrophils and thrombocytes were pooled from two phase 1 studies in 90 patients with advanced solid tumours, receiving namitecan as a 2 h infusion on days 1 and 8 every 3 weeks (D1,8) (n = 34), once every 3 weeks (D1) (n = 29) and on 3 consecutive days (D1–3) (n = 27). A linear three compartment PK model was coupled to a semiphysiological PD‐model for neutrophils and thrombocytes. Data simulations were used to interrogate various dosing regimens and give dosing recommendations.ResultsClearance was estimated to be 0.15 l h–1, with a long terminal half‐life of 48 h. Body surface area was not associated with clearance, supporting flat‐dosing of namitecan. A significant and clinically relevant association was found between namitecan area under the concentration–time curve (AUC) and the percentage drop of neutrophils (r2 = 0.51, P < 10−4) or thrombocytes (r2 = 0.49, P < 10−4). With a target for haematological dose‐limiting toxicity of <20%, the recommended dose was defined as 12.5 mg for the D1,8 regimen, 23 mg for the once every 3 week regimen and 7 mg for the D1–3 regimen.ConclusionThis is the first integrated population PK–PD analysis of the new hydrophilic topoisomerase I inhibitor namitecan, that is currently undergoing early clinical development. A distinct relationship was found between drug exposure and haematological toxicity, supporting flat‐dosing once every 3 weeks as the most adequate dosing regimen.

2015-04-01·Investigational New Drugs3区 · 医学

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors

3区 · 医学

Article

作者: E. Gallerani ; D. Hess ; A. Delmonte ; M. Joerger ; C. Sessa ; P. Barbieri ; S. Pace

PURPOSEThis is a first-in-human, phase I, dose-escalation study to determine the maximum tolerated dose (MTD) of intravenous, flat-dosed ST-1968 (namitecan), a new hydrophilic camptothecan derivative.METHODSNamitecan was administered intravenously over 2 h on day 1 and day 8 every 21 days (D1-D8-Q21D), starting at a flat dose of 2.5 mg, and increased according to a 3 + 3 cohort design. Due to frequent skipping of day 8 dosing for cytopenias, the study was expanded to test namitecan dosing on day 1 every 21 days (D1-Q21) at a starting dose of 17.5 mg. Major dose-limiting toxicity (DLT) was defined as grade (G) 4 neutropenia persisting >5 days, febrile neutropenia, G3 thrombocytopenia or G2 non-hematological toxicity.RESULTSThirty-four patients were included into the D1-D8-Q21D group (2.5, 5, 10, 15, 17.5, 20 mg dosing cohorts), 29 patients into the D1-21D group (17.5, 20, 23, 27, 30 mg dosing cohorts). Neutropenia was the DLT in both groups, with 15 mg being defined as the recommended dose (RD) for the D1-D8-Q21D group, and 23 mg for the D1-Q21D group. Non-hematological toxicity was negligible. One patient with endometrial cancer in the D1-D8-Q21D group and one patient with cholangiocellular carcinoma in the D1-Q21D group experienced a partial remission. Namitecan exhibited fully dose-proportional pharmacokinetics.CONCLUSIONSThis study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen.

2014-04-01·Annals of Hematology

Improvement in hereditary hemorrhagic telangiectasia after treatment with the phosphoinositide 3-kinase inhibitor BKM120

Letter

作者: Ha-Long P. Nguyen ; Urban W. Geisthoff ; Dagmar Hess

Dear Editor, Hereditary hemorrhagic telangiectasia (HHT, Rendu–Osler– Weber syndrome) is an inherited vascular dysplasia. Typical signs are mucocutaneous telangiectases, epistaxis, gastrointestinal bleeding, anemia, and problems due to large visceral vascular shunts [1]. Little is known about the underlying molecular pathogenetic mechanism; however, unbalanced angiogenesis involving the transforming growth factor-β and vascular endothelial growth factor (VEGF) signaling pathways has been assumed [1]. Phosphoinositide 3-kinase (PI3K) signaling plays an important role in the vascular system via VEGF signaling [2]. Here, we report about a patient with HHT who showed an impressive response during treatment with the pan-class I PI3K inhibitor BKM120. Informed consent was obtained from the patient for publication of this observation. The submission of the manuscript has been approved by the institutional review board (“Studienkommission”) of the Hospitals of the City of Cologne. A 49-year-old woman had a positive family history for HHT, long-standing epistaxis, mucocutaneous telangiectases, and anemia. Genetic testing revealed a frameshift mutation in the Activin receptor-like kinase-1 gene (HHT2). In April 2009, a stage IV serous–papillary ovarian cancer was diagnosed. She received surgery and several lines of chemotherapy containing carboplatin, cisplatin, paclitaxel, and namitecan (a camptothecin derivative) until September 2011. Up to this date, epistaxis had been quite stable for several years, occurring several times a day (Table 1) and was unaffected by these therapies. From November 2011 to March 2012, the patient received treatment as part of a phase I trial consisting of four cycles of weekly paclitaxel (80 mg/m iv; days 1, 8, 15, 22; q28 days) and continuous daily BKM120 (100 mg flat dose orally). After the first treatment with BKM120, the patient noted a dramatic decrease in the frequency of epistaxis, which then completely stopped after 6 weeks of therapy. When the ovarian cancer progressed, the patient was switched to a treatment with epirubicin and pazopanib from April 2012 to June 2012. In July 2012, approximately 4 months after the last dose of BKM120 was given, the patient began to experience infrequent mild bleeding from her nose again (Table 1). The bleeding was often initiated by digital manipulation when cleaning the nose, and it did not seem to progress over time. Hemoglobin levels are not discussed in this report as there are many confounding parameters such as chemotherapy, intravenous iron substitution, uncertainty about gastrointestinal involvement, and rare transfusions. U. W. Geisthoff (*) Department of Otorhinolaryngology, Holweide Hospital, Hospitals of the City of Cologne, Cologne, Germany e-mail: geisthoffu@kliniken-koeln.de URL: www.geisthoff.de

100 项与 Namitecan 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12124

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
实体瘤	临床1期	瑞士	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO2011	临床1期	HR阳性/HER2低表达实体瘤	16	Namitecan	(繭範齋齋願遞繭齋淵鹽) = lasting 10+ months 襯鏇築簾積獵鏇淵繭獵 (繭壓鬱鹽鹹鏇製願淵築 ) 更多	-	2011-05-20
ASCO2009	临床1期	HR阳性/HER2低表达实体瘤	31	Namitecan	(鑰艱鏇壓憲顧製築鹽鏇) = 遞選構艱選衊願鹽夢願積壓鹽鑰網網蓋糧製鑰 (構願衊齋選簾網鑰簾願 ) 更多	-	2009-05-20