Welcome!

News Feed Item

Adherex Announces Results From Two Sodium Thiosulfate Phase 3 Studies Presented at the 50th American Society of Clinical Oncology (ASCO) Meeting

-COG STUDY ACCL0431 meets primary endpoint for prevention of cisplatin-induced hearing loss in children

RESEARCH TRIANGLE PARK, NORTH CAROLINA -- (Marketwired) -- 06/02/14 -- Adherex Technologies, Inc. (TSX:AHX)(OTCQB:ADHXF) today announced the results on the two Sodium Thiosulfate (STS) Phase III studies presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

COG ACCL0431

David Freyer, DO, MS, Children's Hospital Los Angeles, COG ACCL0431 Study Chair, presented, "The Effects of Sodium Thiosulfate (STS) on Cisplatin-induced Hearing Loss: A Report from the Children's Oncology Group," in an oral presentation on June 1, 2014.

Study Design

COG Study ACCL0431, "A Randomized Phase III Study of Sodium Thiosulfate for the Prevention of Cisplatin-Induced Ototoxicity in Children," finished enrollment of 131 patients in Q1 2012. The patients had been previously diagnosed with childhood cancers.

The primary endpoint was to evaluate the efficacy of STS for prevention of hearing loss in children receiving cisplatin chemotherapy (hypothesis: 50% relative reduction in hearing loss)

Secondary endpoints included:


--  Compare change in mean hearing thresholds 
--  Compare incidence of other Grade 3/4 toxicities (renal and
    hematological) 
--  Monitor Event Free Survival (EFS) and Overall Survival (OS) in two
    groups 

Preliminary Results

126 eligible subjects were enrolled with germ cell tumor (32), osteosarcoma (30), neuroblastoma (26), medulloblastoma (26), hepatoblastoma (7) or other (5). Of these 104 subjects (64 male and 29 less than 5 years old) were evaluable for the primary endpoint.

Subjects were randomized either to no treatment (control) or treatment with STS 16 grams/m2 IV over 15 minutes 6 hours after each cisplatin dose. Hearing was measured using standard audiometry for age and data were reviewed centrally using American Speech-Language-Hearing Association criteria.

The proportion of subjects with hearing loss assessed at 4 weeks post the final cisplatin dose (primary endpoint) and EFS/OS (log-rank test, 2-year cumulative estimates and Cox proportional hazards model) were compared between the two groups.


--  The proportion of hearing loss for STS vs. Control was 28.6% (14/49) vs.
    56.4% (31/55), respectively (p=0.004). 
--  Including all 126 subjects at median post-enrollment follow-up of 2.9
    years for censored patients, EFS for STS vs. Control was 61.2% vs. 69.9%
    (p=0.31); OS was 77.0% vs. 88.9% (p=0.029). 

A subset analysis by extent of disease determined post hoc was performed:


--  For subjects with localized disease, EFS for STS (N=40) vs. Control
    (N=38) was 72.5% vs. 68.3% (p=0.94); HR (hazard ratio) 1.03 (p=0.94); OS
    was 89.0% vs. 89.5% (p=0.48); HR 1.58 (p=0.48). 
--  For those with disseminated (metastatic) disease, EFS for STS (N=21) vs.
    Control (N=26) was 41.6% vs. 72.5% (p=0.085); HR 2.13 (p=0.092); OS was
    55.9% vs. 88.1% (p=0.011); HR 3.97 (p=0.019).  

Preliminary Conclusions


--  STS protects against cisplatin-induced hearing loss in children,
    especially for those less than 5 years old. 
--  In this study, use of STS did not result in lower EFS/OS in patients
    with localized disease. However, the lower survival among those with
    disseminated disease raises the concern of a tumor protective effect
    when STS is administered on this dose and schedule. 

"Cisplatin-induced hearing loss seriously diminishes quality of life by causing hearing loss in many childhood cancer survivors and impairing their speech, general learning, social development, and confidence," stated Dr. Freyer, "The Children's Oncology Group is pleased to have successfully completed the first pediatric cooperative group clinical trial solely focused on finding a safe and effective means for preventing cisplatin-induced hearing loss. We appreciate the commitment Adherex has made to supporting this research and preserving quality of life in this group of long-term survivors."

SIOPEL 6

Edward A. Neuwelt, M.D., Professor at Oregon Health & Science University presented the ongoing safety results from SIOPEL 6 on behalf of the SIOPEL 6 investigators and support team in a poster on June 2, 2014.

Study Design

SIOPEL 6 study, "A Multicenter Open Label Randomized Phase III Trial of the Efficacy of Sodium Thiosulfate in Reducing Ototoxicity in Patients Receiving Cisplatin Chemotherapy for Standard Risk Hepatoblastoma," is being conducted by The International Childhood Liver Tumour Strategy Group, SIOPEL. The study was initiated in October 2007 and has enrolled 105 out of a planned 115 patients (to achieve 102 evaluable). Interim efficacy results on response to chemotherapy are evaluated after every 20 patients and reviewed by the Independent Data Monitoring Committee (IDMC).

The primary objectives of the study are:


--  To assess the efficacy of STS to reduce the hearing impairment caused by
    cisplatin 
--  To carefully monitor any potential impact of STS on response to
    cisplatin and survival 

The primary endpoint of the study is centrally reviewed absolute hearing threshold, at the age of greater than or equal to3.5 yrs, by pure tone audiometry, graded by Brock criteria.

Methods


--  Newly diagnosed patients with standard risk hepatoblastoma are treated
    with 4 chemotherapy courses every 2 weeks before surgery and 2 courses
    after surgery. 
--  Patients are randomly assigned to receive cisplatin alone or cisplatin
    followed by STS. Cisplatin 80 mg/m2 is administered i.v. over 6 hrs. 
--  STS is administered i.v. exactly 6 hrs after stop of cisplatin over 15
    minutes at 20g/m2. 

Interim Safety Results

The Independent Data Monitoring Committee (IDMC) reviewed the efficacy results of the trial after 20, 40, 60, and 80 patients to assess and rule out any potential concern of an adverse effect of STS on the efficacy of the cisplatin chemotherapy. The IDMC recommends the continuation of the trial according to protocol.

"These results from David Freyer et al are extremely encouraging for the SIOPEL 6 study. SIOPEL 6 is a Phase III randomised trial looking at STS otoprotection in cisplatin treated patients with standard risk hepatoblastoma where the disease is localised, where there is a tumour marker to follow response to treatment, and where survival is over 90%," stated Penelope Brock, MD, PhD, FRCPCH, International Chair of SIOPEL 6, "The average age at diagnosis is 18 months and these children receive cisplatin monotherapy and surgery. The majority of these children fall into the group less than 5 yrs at diagnosis where they are likely to be cured with cisplatin alone and surgery but they sustain bilateral permanent hearing loss for life. Following the safety analysis of the first 80 patients on the SIOPEL 6 trial the IDMC advises continuation of the trial. Therefore if the otoprotection from STS is as good as in the trial presented by Freyer et al then the SIOPEL 6 results are likely to be very encouraging indeed. It is particularly in children with a good prognosis and localised disease where cisplatin is the most effective chemotherapy that we need to be testing otoprotective drugs."

"We wish to thank Drs. Freyer, Brock, and Neuwelt, and all of the participating investigators, support teams and families for their commitment to completing these studies," stated Mr. Rosty Raykov, Chief Executive Officer of Adherex, "We believe the COG results combined with the ongoing safety results from SIOPEL 6 are encouraging for the use of STS in children with localized disease."

Adherex plans to discuss the regulatory filing strategy for a New Drug Application (NDA) with the FDA during the second half of 2014.

Conference Call

Adherex will host a conference call at 3:00 p.m. Eastern Time (2:00 pm Central Time) today to discuss the ASCO results.


Monday, June 2, 2014 @ 3pm Eastern Time                                     
Toll Free:        877-407-0784                                              
International:    201-689-8560                                              
Webcast:          http://public.viavid.com/player/index.php?id=109338       
                                                                            
Replays Available through June 16, 2014:                                    
Toll Free:        877-870-5176                                              
International:    858-384-5517                                              
Passcode:         13583100                                                  

About Sodium Thiosulfate (STS)

STS is currently FDA-approved as an antidote for cyanide poisoning. Adherex has licensed from Oregon Health & Science University intellectual property rights for the use of STS as a chemoprotectant, and are developing STS as a protectant against the hearing loss often caused by platinum-based anti-cancer agents in children. Preclinical and clinical studies conducted by Oregon Health & Science University and others have indicated that STS can effectively reduce the incidence of hearing loss caused by platinum-based anti-cancer agents. Adherex has received Orphan Drug Designation in the United States for the use of STS in the prevention of platinum induced ototoxicity in pediatric patients.

Hearing loss among children receiving platinum-based chemotherapy is frequent, permanent and often severely disabling. The incidence of hearing loss in these children depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids. There is currently no established preventive agent for this hearing loss and only expensive, technically difficult and sub-optimal cochlear (inner ear) implants have been shown to provide some benefit.

Forward Looking Statements

Except for historical information described in this press release, all other statements are forward-looking. Forward-looking statements are subject to certain risks and uncertainties inherent in the Company's business that could cause actual results to vary, including such risks that regulatory clinical and guideline developments may change, scientific data may not be sufficient to meet regulatory standards or receipt of required regulatory clearances or approvals, clinical results may not be replicated in actual patient settings, protection offered by the Company's patents and patent applications may be challenged, invalidated or circumvented by its competitors, the available market for the Company's products will not be as large as expected, the Company's products will not be able to penetrate one or more targeted markets, revenues will not be sufficient to fund further development and clinical studies, the Company may not meet its future capital needs, and its ability to obtain additional funding, as well as uncertainties relative to varying product formulations and a multitude of diverse regulatory and marketing requirements in different countries and municipalities, and other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission including its Annual Report on Form 10-K for the year ended December 31, 2013. Adherex Technologies, Inc. disclaims any obligation to update these forward-looking statements except as required by law.

For a more detailed discussion of related risk factors, please refer to our public filings available at www.sec.gov andwww.sedar.com.

Contacts:
Adherex Technologies Inc.
Rosty Raykov
Chief Executive Officer
(919) 636-5144

More Stories By Marketwired .

Copyright © 2009 Marketwired. All rights reserved. All the news releases provided by Marketwired are copyrighted. Any forms of copying other than an individual user's personal reference without express written permission is prohibited. Further distribution of these materials is strictly forbidden, including but not limited to, posting, emailing, faxing, archiving in a public database, redistributing via a computer network or in a printed form.

Latest Stories
Five years ago development was seen as a dead-end career, now it’s anything but – with an explosion in mobile and IoT initiatives increasing the demand for skilled engineers. But apart from having a ready supply of great coders, what constitutes true ‘DevOps Royalty’? It’ll be the ability to craft resilient architectures, supportability, security everywhere across the software lifecycle. In his keynote at @DevOpsSummit at 20th Cloud Expo, Jeffrey Scheaffer, GM and SVP, Continuous Delivery Busine...
In his session at @ThingsExpo, Eric Lachapelle, CEO of the Professional Evaluation and Certification Board (PECB), provided an overview of various initiatives to certify the security of connected devices and future trends in ensuring public trust of IoT. Eric Lachapelle is the Chief Executive Officer of the Professional Evaluation and Certification Board (PECB), an international certification body. His role is to help companies and individuals to achieve professional, accredited and worldwide re...
SYS-CON Events announced today that TechTarget has been named “Media Sponsor” of SYS-CON's 21st International Cloud Expo, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. TechTarget storage websites are the best online information resource for news, tips and expert advice for the storage, backup and disaster recovery markets.
The current age of digital transformation means that IT organizations must adapt their toolset to cover all digital experiences, beyond just the end users’. Today’s businesses can no longer focus solely on the digital interactions they manage with employees or customers; they must now contend with non-traditional factors. Whether it's the power of brand to make or break a company, the need to monitor across all locations 24/7, or the ability to proactively resolve issues, companies must adapt to...
You know you need the cloud, but you’re hesitant to simply dump everything at Amazon since you know that not all workloads are suitable for cloud. You know that you want the kind of ease of use and scalability that you get with public cloud, but your applications are architected in a way that makes the public cloud a non-starter. You’re looking at private cloud solutions based on hyperconverged infrastructure, but you’re concerned with the limits inherent in those technologies.
"Loom is applying artificial intelligence and machine learning into the entire log analysis process, from start to finish and at the end you will get a human touch,” explained Sabo Taylor Diab, Vice President, Marketing at Loom Systems, in this SYS-CON.tv interview at 20th Cloud Expo, held June 6-8, 2017, at the Javits Center in New York City, NY.
@DevOpsSummit at Cloud Expo taking place Oct 31 - Nov 2, 2017, at the Santa Clara Convention Center, Santa Clara, CA, is co-located with the 21st International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The widespread success of cloud computing is driving the DevOps revolution in enterprise IT. Now as never before, development teams must communicate and collaborate in a dynamic, 24/7/365 environment. There is ...
SYS-CON Events announced today that Datanami has been named “Media Sponsor” of SYS-CON's 21st International Cloud Expo, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. Datanami is a communication channel dedicated to providing insight, analysis and up-to-the-minute information about emerging trends and solutions in Big Data. The publication sheds light on all cutting-edge technologies including networking, storage and applications, and the...
After more than five years of DevOps, definitions are evolving, boundaries are expanding, ‘unicorns’ are no longer rare, enterprises are on board, and pundits are moving on. Can we now look at an evolution of DevOps? Should we? Is the foundation of DevOps ‘done’, or is there still too much left to do? What is mature, and what is still missing? What does the next 5 years of DevOps look like? In this Power Panel at DevOps Summit, moderated by DevOps Summit Conference Chair Andi Mann, panelists loo...
SYS-CON Events announced today that EnterpriseTech has been named “Media Sponsor” of SYS-CON's 21st International Cloud Expo, which will take place on Oct 31 – Nov 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA. EnterpriseTech is a professional resource for news and intelligence covering the migration of high-end technologies into the enterprise and business-IT industry, with a special focus on high-tech solutions in new product development, workload management, increased effi...
For organizations that have amassed large sums of software complexity, taking a microservices approach is the first step toward DevOps and continuous improvement / development. Integrating system-level analysis with microservices makes it easier to change and add functionality to applications at any time without the increase of risk. Before you start big transformation projects or a cloud migration, make sure these changes won’t take down your entire organization.
Cloud promises the agility required by today’s digital businesses. As organizations adopt cloud based infrastructures and services, their IT resources become increasingly dynamic and hybrid in nature. Managing these require modern IT operations and tools. In his session at 20th Cloud Expo, Raj Sundaram, Senior Principal Product Manager at CA Technologies, will discuss how to modernize your IT operations in order to proactively manage your hybrid cloud and IT environments. He will be sharing bes...
A look across the tech landscape at the disruptive technologies that are increasing in prominence and speculate as to which will be most impactful for communications – namely, AI and Cloud Computing. In his session at 20th Cloud Expo, Curtis Peterson, VP of Operations at RingCentral, highlighted the current challenges of these transformative technologies and shared strategies for preparing your organization for these changes. This “view from the top” outlined the latest trends and developments i...
Automation is enabling enterprises to design, deploy, and manage more complex, hybrid cloud environments. Yet the people who manage these environments must be trained in and understanding these environments better than ever before. A new era of analytics and cognitive computing is adding intelligence, but also more complexity, to these cloud environments. How smart is your cloud? How smart should it be? In this power panel at 20th Cloud Expo, moderated by Conference Chair Roger Strukhoff, paneli...
Hardware virtualization and cloud computing allowed us to increase resource utilization and increase our flexibility to respond to business demand. Docker Containers are the next quantum leap - Are they?! Databases always represented an additional set of challenges unique to running workloads requiring a maximum of I/O, network, CPU resources combined with data locality.