A Single-Center, Double-Blind, Randomized, Placebo- and Positive-Controlled, Parallel Group, Thorough QT/QTc Study to Evaluate the Effect of Custirsen (640 mg) on Cardiac Repolarization in Healthy Men

This is a 3-arm, parallel-group, active- and placebo-controlled, double-blind, randomized study, to compare treatment with intravenous custirsen at 640 mg (highest intended therapeutic dose) with placebo. The purpose of this study is to assess the effect of custirsen treatment on cardiac conduction and repolarization (electrical activity of the heart) in healthy subjects. The positive control employed to demonstrate assay sensitivity consists of a group receiving a single oral dose of 400 mg moxifloxacin on day 7. The moxifloxacin arm is un-blinded but the ECG readings are blinded.

Start Date01 May 2013

Sponsor / Collaborator

Achieve Life Sciences, Inc.

[+1]

NCT01630733 / Unknown statusPhase 3

A Multinational, Randomized, Open-Label Phase III Study of Custirsen (TV-1011/OGX-011) In Combination With Docetaxel Versus Docetaxel As A Second-Line Treatment In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer

The primary objective of the study is to compare overall survival of patients randomized to receiving custirsen in combination with docetaxel (Arm A) with patients randomized to receive docetaxel alone (Arm B).

Start Date01 Sep 2012

Sponsor / Collaborator

Achieve Life Sciences, Inc.

NCT01578655 / CompletedPhase 3

A Randomized Phase 3 Study Comparing Cabazitaxel/Prednisone in Combination With Custirsen (OGX-011) to Cabazitaxel/Prednisone for Second-Line Chemotherapy in Men With Metastatic Castrate Resistant Prostate Cancer (AFFINITY)

This Phase 3 study has been designed to confirm that adding custirsen to cabazitaxel/prednisone treatment can slow tumor progression and enhance survival outcomes compared to standard cabazitaxel/prednisone treatment in men with metastatic castrate resistant prostate cancer (CRPC). This will be a randomized, open-label, multicenter, international trial. Treatment will consist of cabazitaxel/prednisone/custirsen vs. cabazitaxel/prednisone. A total of approximately 630 patients will be randomized with equal probability to the two arms.

Start Date01 Aug 2012

Sponsor / Collaborator

Achieve Life Sciences, Inc.

100 Clinical Results associated with Custirsen Sodium

100 Translational Medicine associated with Custirsen Sodium

100 Patents (Medical) associated with Custirsen Sodium

Literatures (Medical) associated with Custirsen Sodium

01 Jul 2023·The Journal of urology

LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer.

Article

INTRODUCTION AND OBJECTIVE:

Within 10 years following definitive therapy for prostate cancer, ∼20-50% of patients (pts) experience biochemical recurrence (BCR) characterized by rising prostate-specific antigen (PSA) levels. Pts with high-risk BCR have an increased risk of mortality and improved therapies are needed. The objective of EMBARK was to evaluate the efficacy and safety of enzalutamide (enza) + androgen deprivation therapy (ADT) and enza monotherapy (mono) in pts with high-risk BCR.

METHODS:

EMBARK is a randomized, phase 3 study of pts with BCR considered high-risk: PSA doubling time ≤9 months and PSA ≥2 ng/mL above nadir post-radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy (RP) ± postoperative RT. Pts were randomized (1:1:1) to enza 160 mg/day + leuprolide acetate (LA) (double-blind), placebo (pbo) + LA (double-blind), or enza mono (open-label). LA 22.5 mg was administered every 12 weeks. If the PSA at week 36 was <0.2 ng/mL, therapy was stopped at week 37 and restarted when PSA was ≥2 ng/mL for pts with primary RP, and ≥5 ng/mL for pts without RP. The primary endpoint, determined by blinded, independent central review (BICR), was metastasis-free survival (MFS) with enza + LA vs pbo + LA. Key secondary endpoints were MFS of enza mono vs pbo + LA, time to PSA progression, time to antineoplastic therapy, and overall survival (OS) of enza + LA or enza mono vs pbo + LA.

RESULTS:

1068 pts were randomized into the study (enza + LA, n=355; pbo + LA, n=358; enza mono, n=355). After median follow-up of 60.7 months, per BICR, MFS for enza + LA (HR 0.42; 95% CI 0.30-0.61; p<0.0001) and enza mono (HR 0.63; 95% CI 0.46-0.87; p=0.0049) were statistically superior to pbo + LA. Statistically significant improvements were also observed in risk of PSA progression (enza + LA: HR 0.07; 95% CI, 0.03-0.14; enza mono: HR 0.33; 95% CI, 0.23-0.49; both p<0.0001) and time to first use of new antineoplastic therapy (enza + LA: HR 0.36; 95% CI, 0.26-0.49; enza mono: HR 0.54; 95% CI, 0.41-0.71; both p<0.0001). Interim OS data trended in favor enza + LA (HR 0.59; 95% CI, 0.38-0.91; p=0.0153, did not cross interim efficacy boundary) and enza mono (HR 0.78; 95% CI, 0.52-1.17; p=0.2304). Fatigue and hot flash were the most common adverse events; no new safety signals were observed.

CONCLUSIONS:

In pts with high-risk BCR, enza + ADT and enza mono demonstrated a statistically significant and clinically meaningful improvement in MFS vs pbo + ADT. The safety profile of enza was consistent with results from previous clinical studies.

CLINICAL TRIAL REGISTRATION NUMBER:

NCT02319837.

SOURCE OF FUNDING:

Pfizer Inc. and Astellas Pharma Inc.Conflict of Interest and Disclosure Statement:Neal D. Shore reports grant support and consulting fees from AbbVie, Amgen, Astellas Pharma Inc., AstraZeneca, Bayer, Clovis Oncology, Dendreon Pharmaceuticals LLC, Ferring Pharmaceuticals, GenesisCare, Janssen Oncology, Merck, Myovant Sciences, Pfizer Inc., Sanofi-Genzyme, and Tolmar Pharmaceuticals, Inc. Murilo de Almeida Luz reports receiving speaker honoraria from Astellas Pharma Inc., Bayer, Janssen, Merck Sharp & Dohme, and Pfizer Inc.; being an advisory board member for Astellas Pharma Inc., Bayer, and Janssen; sponsored research from Bayer, Bristol Myers Squibb, Ferring Pharmaceuticals, GlaxoSmithKline, Janssen, and Roche; receiving travel expenses from AstraZeneca, Bayer, Janssen, and Pfizer Inc. Ugo De Giorgi reports serving as a consultant for Janssen, Astellas Pharma Inc., Sanofi, Bayer, Pfizer Inc., Bristol Myers Squibb, Novartis, Ipsen, and Merck Sharp & Dohme. Martin Gleave reports stock or ownership interest in OncoGenex Technologies Inc., Sustained Therapeutics Inc., and Sikta Biopharma; is a consultant to Astellas Pharma Inc., AstraZeneca, Bayer, Genova Diagnostics (GDx), Janssen, Pfizer Inc., Roche, Sanofi, and TerSera Therapeutics LLC; and holds patents for OGX-011, OGX-427, ST-CP, and ST-POP. Geoffrey T. Gotto reports receiving honoraria from Amgen, Astellas Pharma Inc., Bayer, Ferring Pharmaceuticals, Janssen, and Merck; being a consultant or advisory board member for Amgen, Astellas Pharma Inc., Bayer, Janssen, and Merck; providing expert testimony for Janssen; and receiving support for travel, accommodation, and expenses from Janssen. Gabriel P. Haas reports being an employee of and shareholder in Astellas Pharma Inc. Miguel Ramirez-Backhaus reports serving as a consultant or advisory board member for Astellas Pharma Inc., Bayer, Janssen, and Karl Storz; receiving speaker honoraria from Astellas Pharma Inc., Bayer, Janssen, and GP Pharm. Antti Rannikko reports being a board member for the Ida Montin Foundation, and Orion Research Foundation; being an advisory board member for Bayer, Janssen, and Orion Pharma; being a stockholder and clinical advisor for Aqsens Health; being a clinical investigator for Astellas Pharma Inc., Bayer, Janssen, Orion Pharma, and RhoVac AB; and receiving competitive state research funding from HUS Helsinki University Hospital, Finnish Cancer Organizations, and the Jane and Aatos Erkko Foundation. Jamal Tazari, Yiyun Tang, and Fabian Zohren are employees of and shareholders in Pfizer Inc. Swetha Sridharan reports no conflicts of interest. Jennifer Sugg is an employee of Astellas Pharma Inc., and a shareholder in AstraZeneca. Ronald F. Tutrone, Jr. reports being an advisory board member for Bayer; and receiving speaker honoraria from Astellas Pharma Inc., Exosome Diagnostics, Inc., Myovant Sciences, and Pfizer Inc. Balaji Venugopal reports receiving honoraria from Bristol Myers Squibb, Eisai Co., Ltd, EUSA Pharma, Ipsen, Janssen, and Merck; being a consultant or advisory board member for Janssen, Merck Sharp & Dohme Oncology, and Pfizer Inc./EMD Serono; and receiving support for travel, accommodation, and expenses from EUSA Pharma, and Ipsen. Arnauld Villers reports receiving research grants from Astellas Pharma Inc., Ferring Pharmaceuticals, Ipsen, and Janssen. Henry H. Woo reports being an advisory board member for Astellas Pharma Inc., Bayer, Boston Scientific Corporation, and Mundipharma International Ltd; and reports receiving speaker honoraria from AbbVie, Astellas Pharma Inc., Boston Scientific Corporation, and Janssen. Stephen J. Freedland reports being a consultant for Astellas Pharma Inc., AstraZeneca, Bayer, Dendreon Pharmaceuticals LLC, Janssen, Merck, Myovant Sciences, Pfizer Inc., and Sanofi.

ACKNOWLEDGMENTS:

The authors thank all the patients, their families, and the investigators and investigational site members involved in this study.Editorial Acknowledgement:Medical writing and editorial support was provided by Julie B. Stimmel, PhD, Sinead Stewart, and Rosie Henderson, of Onyx (a Prime Global Agency), funded by Pfizer, Inc. and Astellas Pharma Inc., the co-developers of enzalutamide.Submission Category:prostate cancer.Sub-category:Advanced (including drug therapy).

01 Feb 2021·Advanced science (Weinheim, Baden-Wurttemberg, Germany)Q1 · MATERIALS SCIENCE

Inhibition Lysosomal Degradation of Clusterin by Protein Kinase D3 Promotes Triple‐Negative Breast Cancer Tumor Growth

Q1 · MATERIALS SCIENCE

ArticleOA

Author: Liu, Yan ; Zhou, Yehui ; Ma, Xinxing ; Chen, Liming

Abstract:

Triple negative breast cancer (TNBC), with its lack of targeted therapies, shows the worst mortality rate among all breast cancer subtypes. Clusterin (CLU) is implicated to play important oncogenic roles in cancer via promoting various downstream oncogenic pathways. Here, protein kinase D3 (PRKD3) is defined to be a key regulator of CLU in promoting TNBC tumor growth. Mechanically, PRKD3 with kinase activity binding to CLU is critical for CLU protein stability via inhibiting CLU's lysosomal distribution and degradation. CLU and PRKD3 protein level are significantly elevated and positively correlated in collected TNBC tumor samples. CLU silencer (OGX‐011) and PRKDs inhibitor (CRT0066101) can both result in impressive tumor growth suppression in vitro and in vivo, suggesting targeting CLU and its key regulator‐PRKD3 are promisingly efficient against TNBC. Finally, secreted CLU (sCLU) is found to be elevated in serums from TNBC patients and reduced in serum from TNBC murine models post OGX‐011 and/or CRT0066101 treatment, suggesting serum sCLU is a promising blood‐based biomarker for clinical management of TNBC. Taken together, this study provides a thorough molecular basis as well as preclinical evidences for targeting CLU pathway as a new promising strategy against TNBC via revealing PRKD3 as the key regulator of CLU in TNBC.

07 Jun 2020·Current medicinal chemistryQ2 · MEDICINE

Secretory Clusterin as a Novel Molecular-targeted Therapy for Inhibiting Hepatocellular Carcinoma Growth

Q2 · MEDICINE

Review

Author: Wang, Li ; Zheng, Wenjie ; Yao, Min ; Yao, Dengfu ; Sai, Wenli ; Dong, Zhizhen

Background::

Although secretory clusterin (sCLU) plays a crucial role in Hepatocellular Carcinoma (HCC) cells proliferation, Multiple Drug Resistance (MDR), metastasis and so on, its targeted effects and exact mechanism are still unknown. This review summarizes some new progress in sCLU as a molecular-targeted therapy in the treatment of HCC.

Methods::

A systematic review of the published English-language literature about sCLU and HCC has been performed using the PubMed and bibliographic databases. Some valuable studies on sCLU in HCC progression were searched for relevant articles with the keywords: HCC, diagnosis, MDR, as molecular-targeted in treatment, and so on.

Results::

The incidence of the positive rate of sCLU was significantly higher in HCC tissues as compared to the surrounding tissues at mRNA or protein level, gradually increasing with tumor-nodemetastasis staging (P<0.05). Also, the abnormal level of sCLU was related to poor differentiation degree, and considered as a useful marker for HCC diagnosis or independent prognosis for patients. Hepatic sCLU could be silenced at mRNA level by specific sCLU-shRNA or by OGX-011 to inhibit cancer cell proliferation with an increase in apoptosis, cell cycle arrest, reversal MDR, alteration of cell migration or invasion behaviors, and a decrease in GSK-3β or AKT phosphorylation in vitro, as well as significant suppression of the xenograft growth by down-regulating β-catenin, p-GSK3β, and cyclinD1 expression in vivo.

Conclusion::

Abnormal hepatic sCLU expression should not only be a new diagnostic biomarker but also a novel promising target for inhibiting HCC growth.

News (Medical) associated with Custirsen Sodium

08 Mar 2007

·www.biospace.com

OncoGenex Technologies Inc. Withdraws Initial Public Offering

VANCOUVER, March 7 /PRNewswire/ - OncoGenex Technologies Inc. announced today that the company has withdrawn its registration statement from the U.S. Securities and Exchange Commission, citing market conditions as a deterrent to completing its initial public offering. "Due to the recent adverse market conditions, we have decided not to move forward with an initial public offering at this time," stated Scott Cormack, President and Chief Executive Officer of OncoGenex. "We anticipated pricing our initial public offering on February 27, coincidentally the same day that the equity markets suffered the largest one-day decline in four years. Given current market conditions, we believe it is in our shareholders' best interest to withdraw our initial public offering and continue to focus on delivering results from our phase 2 programs. "We have the resources to complete our five ongoing phase 2 clinical trials with our lead product candidate, OGX-011, in prostate, breast and non-small cell lung cancers," added Cormack. "We expect to have primary endpoint data from all five of these trials by the end of this year, and we look forward to reporting data in the appropriate forums." About OncoGenex OncoGenex is committed to the development and commercialization of new cancer therapies that address treatment resistance in cancer patients. OncoGenex currently has three product candidates in development: OGX-011, OGX-427 and OGX-225. These product candidates are designed to selectively inhibit the production of proteins that are associated with treatment resistance and that are over-produced in response to a variety of cancer treatments. OncoGenex' aim in targeting these particular proteins is to disable the tumor cells' adaptive defenses, render the tumor cells susceptible to attack with a variety of cancer therapies including chemotherapy, and facilitate tumor cell death. More information on OncoGenex and the company's pipeline is available at . Forward-looking Statements This press release may include forward-looking statements. Statements regarding future events, expectations and beliefs of management and other statements that do not express historical facts, are forward-looking statements. Words such as "believe", "may", "will", "estimate", "continue", "anticipate", "intend", "expect", "plan", "predict", "potential" and similar expressions, as they relate to OncoGenex, our business and our management, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends affecting the financial condition of our business. Forward-looking statements should not be read as a guarantee of future performance or results, and will not necessarily be accurate indications of the times at, or by, which such performance or results will be achieved. Forward-looking statements are based on information available at the time those statements are made and/or management's good faith belief as of that time with respect to future events, and are subject to risks and uncertainties that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking statements. Important factors that could cause such differences include, but are not limited to: delays or unfavorable results from our current and planned clinical trials; our ability to establish and maintain intellectual property protection for our product candidates; our access to additional capital; our ability to enter into and maintain relationships with third parties, such as licensors, manufacturers, suppliers and those who conduct clinical trials for us; our ability to enroll patients for our clinical trials; our ability to implement and manage our sales and commercialization initiatives; the impact of competition and technological change; the timing of necessary regulatory clearances; coverage and reimbursement policies of governmental and private third-party payors, including the U.S. Medicare and Medicaid programs; general economic and business conditions, both nationally and in our markets; our ability to attract and retain key management and scientific personnel; existing and future regulations that affect our business; and other factors included in OncoGenex's filings with the United States Securities and Exchange Commission and the Canadian securities regulators. In light of these risks and uncertainties, forward-looking events and circumstances included in this presentation may not occur and actual results could differ materially from those anticipated or implied in the forward-looking statements. Forward-looking statements speak only as of the date the statements are made. You should not put undue reliance on any forward-looking statements. We assume no obligation to update forward-looking statements to reflect actual results, changes in assumptions or changes in other factors affecting forward-looking information, except to the extent required by applicable securities laws. If we do update one or more forward-looking statements, no inference should be drawn that we will make additional updates with respect to those or other forward-looking statements. CONTACT: OncoGenex Contact: Scott Cormack, President & CEO, (604) 630-5400, scormack@oncogenex.ca; Media Contact: Jason Spark, Porter Novelli Life Sciences, (619) 849-6005, jspark@pnlifesciences.com OncoGenex Technologies Inc. CONTACT: OncoGenex Contact: Scott Cormack, President & CEO, (604)630-5400, scormack@oncogenex.ca; Media Contact: Jason Spark, Porter NovelliLife Sciences, (619) 849-6005, jspark@pnlifesciences.com >>> Discuss This Story

IPO

100 Deals associated with Custirsen Sodium

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KEGG	Wiki	ATC	Drug Bank
D09403	-	-	DB05487

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
metastatic non-small cell lung cancer	Phase 3	US	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	AU	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	DE	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	HU	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	IL	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	IT	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	NZ	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	PL	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	RU	Achieve Life Sciences, Inc.	01 Sep 2012
metastatic non-small cell lung cancer	Phase 3	SG	Achieve Life Sciences, Inc.	01 Sep 2012

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01188187 (SYNERGY, Pubmed \| Lancet Oncol) Manual	Phase 3	Metastatic castration-resistant prostate cancer	1,022	docetaxel+prednisone+custirsen	sazwrvasvc(mrvjpfjdca) = ogasbekdrc lawnhwwqbu (celgpmsurm ) View more	Similar	01 Apr 2017
				docetaxel+prednisone	sazwrvasvc(mrvjpfjdca) = okxwoaxlhk lawnhwwqbu (celgpmsurm ) View more
NCT01630733 (ENSPIRIT, PRNewswire) Manual	Phase 3	Non-Small Cell Lung Cancer Second line	664	Custirsen	tkyukdoxxu(repbowusbl) = uiomzjkgcq brjyybvjty (aquzwhgkix )	Positive	13 Oct 2016
				Docetaxel	tkyukdoxxu(repbowusbl) = oespukgpzs brjyybvjty (aquzwhgkix )
NCT01188187 (SYNERGY, ASCO2015)	Phase 3	Metastatic castration-resistant prostate cancer	1,022	Docetaxel + Custirsen	hxdxtwvbmr(wltajqiohi) = aloecewghp sudegsgqmb (vebvkhhcxz ) View more	Positive	20 May 2015
				Control (Docetaxel alone)	hxdxtwvbmr(wltajqiohi) = jiavamqkiw sudegsgqmb (vebvkhhcxz ) View more
NCT01083615 (ASCO_GU2014)	Phase 3	Neoplasms Second line	35	Custirsen/taxane	nlnctkhozj(chbvlwkbae) = 2,1 ykeqhxvodn (whjxlofdeu ) View more	-	01 Feb 2014
				Placebo/taxane
NCT00327340 (Pubmed \| Cancer Med)	Phase 2	Castration-Resistant Prostatic Cancer Second line	70	Custirsen + mitoxantrone/prednisone	nuhopaetlw(tmlhwoyswa) = raituubivb ddlhdfomcf (zarapqlcns )	-	01 Aug 2013
				Custirsen + docetaxel retreatment/prednisone	nuhopaetlw(tmlhwoyswa) = hshuwbvxzd ddlhdfomcf (zarapqlcns )
NCT00327340 (CUOG Trial P-06c, CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	70	custirsen (OGX-011)/mitoxantrone	uocqdcitzm(ujwksoivsb) = cljbdiysmb txeujnlclq (nxmrofwzip, hlcgtswwyx - jcpbrsozyw) View more	-	29 Aug 2012
Pubmed \| J Clin Oncol	Phase 2	Metastatic castration-resistant prostate cancer prostate-specific antigen	-	Docetaxel/prednisone with OGX-011	kijuiehced(cthmilxaze) = vjyakwrdiu wajkgcmnca (gfavtfkbyn ) View more	Positive	20 Sep 2010
				Docetaxel/prednisone without OGX-011	kijuiehced(cthmilxaze) = uneucnbydc wajkgcmnca (gfavtfkbyn ) View more
ASCO2009	Phase 2	Metastatic castration-resistant prostate cancer	82	OGX-011 + docetaxel/prednisone	vphzyaiyir(vgpzopvcdy) = dzlimgfpem vvdpafskna (fjkwhjibpg ) View more	-	20 May 2009
				docetaxel/prednisone	vphzyaiyir(vgpzopvcdy) = lscozinnyj vvdpafskna (fjkwhjibpg ) View more
ASCO2008	Phase 2	Castration-Resistant Prostatic Cancer	42	Custirsen/docetaxel/prednisone	svgxjohtvd(fzdnxumjgl) = wpgvaaqfcc fefqxwdmvj (eefdtpoosh ) View more	-	20 May 2008
				Custirsen/mitoxantrone/prednisone	svgxjohtvd(fzdnxumjgl) = bwshjxhazq fefqxwdmvj (eefdtpoosh ) View more
ASCO2007	Phase 1/2	Advanced Lung Non-Small Cell Carcinoma First line	85	OGX-011	jxdyixvxbd(kynjwkjkgx) = neutropenia (32%) + thrombocytopenia (17%) ujjucljumm (idetwqmyru )	-	20 Jun 2007

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