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
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
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).
-- 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, "
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 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.
-- 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
"These results from
"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.
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About Sodium Thiosulfate (STS)
STS is currently
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
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Adherex Technologies Inc. Rosty RaykovChief Executive Officer (919) 636-5144 Source: Adherex Technologies Inc.