June 17, 2013

DelMar Pharmaceuticals reported results from a phase I/II trial of VAL-083 (dianhydrogalactitol) for the treatment of recurrent malignant glioma and progressive secondary brain tumors. Of the three cohorts of patients currently enrolled, all have failed standard therapies and have no viable treatment options. The subjects received VAL-083 at a dose of 1.5mg/m; 3.0mg/m and 5.0mg/m. At these doses, 25% (2/8) of GBM patients and 17% (1/6) of secondary-progressive brain cancer patients showed stable disease or tumor regression in response to treatment. VAL-083 therapy is well tolerated in glioblastoma multiforme (GBM) and secondary-progressive brain tumor patients with no drug-related serious adverse events at doses studied to date. DelMar plans to split the protocol into two separate studies: one focusing solely on refractory glioblastoma and the other focusing on metastatic brain cancers.

November 28, 2012

Aeterna Zentaris reported results from a phase I trial of perifosine combined with temsirolimus for the treatment of malignant glioma. This combination, dose-ranging study enrolled 32 patients with recurrent or progressive malignant glioma, anaplastic astrocytoma, anaplastic oligodendroglioma and transformed low-grade gliomas with median Karnofsky Performance Status 80. Subjects either received a 600mg or 900mg dose of perifosine on day one, followed by a nightly dose of 100mg of perifosine. All subjects also received 15mg to170mg of temsirolimus once weekly. Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12). The most frequent adverse events were hypophosphatemia, hypocholesterolemia and hypertriglyceridemia. The maximum tolerated dose was not defined, so Aeterna Zentaris is creating expansion cohorts.

November 7, 2011

YM Biosciences reported preliminary results from a phase II trial of nimotuzumab for pediatrics with recurrent diffuse intrinsic pontine glioma. This open-label, single-arm, multi-center study enrolled 46 subjects aged three to 18 years of age. The subjects received nimotuzumab 150 mg/m2 administered intravenously once weekly from week one to seven and once every two weeks from week eight to 18. Treatment with nimotuzumab was well tolerated with most adverse events reported as mild or moderate in severity. No complete responses (CR) were observed. At week eight, a partial response (PR) was reported in two subjects, stable disease (SD) in six subjects and progressive disease (PD) in 11 subjects who were evaluable for response, resulting in a clinical benefit rate (CR+PR+SD) of 18.2%. At week 18, one subject continued to have a PR and three subjects continued with SD, for an overall response rate of 2.3%. The median duration of response, time to progression, and overall survival were 2.1 months, 1.7 months and 3.2 months respectively.

November 26, 2007

Keryx released positive interim results from a phase II trial of perifosine for the treatment of recurrent malignant glioma. This trial enrolled twenty-five subjects who had failed prior radiation therapy and had evidence of tumor progression. The subjects were treated with a loading dose of 600 mg (150mg x 4) followed by 100 mg daily dose of perifosine. Response was measured by the MacDonald Criteria (partial response greater than or equal to 50% decrease in bidirectional tumor area and stable disease = between 25% worse to 50% better). Out of twenty evaluable subjects, partial response was observed in two, stable disease was observed in four and overall response (partial + stable) was reported in six subjects. The median progression free survival and overall survival was nine weeks and forty-nine weeks, respectively. Treatment was generally well tolerated. Subjects with anaplastic gliomas showed the greatest response, hence the trial planned to continue enrolling only this population.

July 2, 2007

Antisense reported results from a phase IIB trial of AP12009 for the treatment of glioma. This open-label, randomized, actively-controlled, parallel-group dose-finding study enrolled subjects with anaplastic astrocytoma or recurrent glioma. Results are from 134 evaluable subjects who were randomized into one of three arms: AP 12009 (10 micrometers), AP 12009 (80 micrometers) and chemotherapy (Temozolomide or PCV) as control. AP12009 was administered intratumorally via one catheter as continuous high-flow microperfusion over a 7-day period, every other week, for up to 6 months. The tumor response rate (assessed according to Macdonald criteria) for the AP12009 (10 micrometer) arm increased over the course of 14 months while the chemotherapy arm showed a transient peak of the response rate at 6 months that was not sustainable and decreased to zero at 14 months. Response rates were higher in the AP12009 (10 microgram) arm compared to the AP12009 (80 microgram arm). Median overall survival (mOS) in the AP 12009 10 microgram group had not yet been reached, whereas mOS for the control group was 21.1 months. In the AP12009 10 microgram group, 67% of the subjects were still alive compared to 42% in the control group. Antisense is currently undergoing preparations for phase III trials.

October 17, 2005

NeoPharm reported positive interim results of a phase I trial of cintredekin besudotox, for the treatment of malignant glioma, at the 55th Annual Meeting of the Congress of Neurological Surgeons. Trial data collected to date indicate a positive safety profile, with no incidence of grade ¾ hematological toxicities, and an adverse event profile consistent with prior therapies. Secondary efficacy data were also positive, with median survival extended beyond one year. This ongoing open-label study had enrolled 12 treatment-naïve patients to date, who received cintredekin besudotox via convection-enhanced delivery, followed by radiation therapy with or without temozolomide (Temodar).

November 29, 2004

Alteris Therapeutics has announced positive results of a phase I clinical trial of their EGFRvIII peptide therapeutic vaccine, for the treatment of malignant glioma. Results from the trial met their primary safety and tolerability endpoints, with no serious adverse events reported and a favorable tolerability profile. Furthermore, the drug demonstrated significant preliminary evidence of efficacy: 2 patients experienced near-complete remission after vaccination, more than 25% of subjects experienced stable disease state during the study, median overall time to disease progression was 314 days, compared to a historical baseline of I24 days, and median survival time was over 596 days, or about 20 months, compared to a historical baseline of 11-13 months. This open-label safety and efficacy trial enrolled a total of 16 patients with malignant glioma at 1 US site, who received a total of three doses of the trial once every two weeks.

Hybridon has issued positive interim results of a phase I trial of IMOxine, their investigational second-generation immunomodulatory oligonucleotide for the treatment of solid tumors. Results from the 19 subjects completing safety evaluations met primary safety and tolerability endpoints, with no dose-limiting toxicity, a tolerability profile consistent with immune system stimulation, and a manageable adverse event profile including transient hypoxia/dyspnea (n=1), abdominal pain with nausea/vomiting (n=1), and anemia requiring transfusion (n=2). There were 4 early withdrawals, all due to disease progression. Furthermore, results from the 17 subjects completing preliminary efficacy evaluations indicated that the drug produced stable disease state in 53% of patients (n=9) after 8 weeks of treatment, and 1 of these subjects maintained this state into the 11th month of treatment. This open-label, open-duration safety and immunpharmacology study enrolled 23 patients with assorted refractory solid tumors at 1 US site. Subjects received IMOxine via weekly subcutaneous injection at one of 5 dosing regimens (0.04, 0.16, 0.32, 0.48, or 0.64 mg/kg).

Pharmacyclics announced the combined results of two phase I trials of Xcytrin (motexafin gadolinium) in combination with cranial irradiation for the treatment of glioblastoma multiforme (GBM). Data from both trials indicated that the duration-ranging regimens met primary safety and tolerability endpoints, with no drug related interruptions of radiation therapy and a manageable adverse event profile which included numbness, tingling and rash of fingertips, nausea and mild diarrhea, and reversible hepatic chemistry abnormalities. Preliminary evidence indicates that the drug promoted improvements in survival. Specifically, patients receiving a cumulative dose >60 mg/kg of Xcytrin experienced a median survival time of 11.5 months, with 82% alive at 6 months and 46% at 12. Patients a cumulative dose <60mg/kg experienced median survival of 16.4 months, with 93% and 78% alive at 6 and 12 months. Overall median survival for the entire group of patients was 14.7 months, with 91% and 69% alive at 6 and 12 months. Both trials were open-label, cumulative-dose-escalation studies (40-117 mg/kg), which enrolled a combined total of 55 subjects with treatment-naïve GBM.

May 5, 2003

NeoPharm reported positive preliminary results from an ongoing phase I/II trial investigating IL13-PE38QQR, a tumor-targeting agent for the treatment of brain cancer. Results showed cytotoxic effects against malignant glioma tumor cells at a concentration range of .5-2.0 micrograms/mL when infused directly into the tumor. Data showed survival without tumor progression of three to over 90 weeks. In addition, overall survival from time of treatment was 12 to over 90 weeks. The most frequent adverse events reported were headache, sensory symptoms, motor symptoms, aphasia and seizure. The study was designed in three stages to assess the saftey, tolerability and biologic effect of IL13-PE38QQR in addition to surgical resection of recurrent malignant glioma.

September 23, 2002

Long-term survival results of Gliadel Wafer demonstrated the risk of dying was reduced after the wafer implantation. The phase III trial conducted at 38 centers in 14 countries worldwide was a randomized, double-blind, placebo-controlled study involving 240 subjects who had undergone initial surgery resection of high-grade malignant glioma. Each subject was randomly assigned to receive either Gliadel Wafer or placebo wafers into the resection cavity followed by radiation therapy. After the three to four year follow-up, 9 of the 11 surviving subjects had received Gliadel Wafer. The hazard ratio for Gliadel Wafer-treated subjects relative to placebo treated subjects was 0.73, indicating a reduction in the risk of dying by 27%. Gliadel Wafer is being developed by Guilford Pharmaceuticals.

Results from a phase II/III trial involving 138 subjects for the treatment of ulcerative colitis indicated deligoparin did not meet the primary or secondary endpoints of the study. Subjects receiving standard treatment were administered either deligoparin by subcutaneous injection or placebo once a day for six weeks. Although the drug proved to be safe, Incara Pharmaceuticals and Elan Pharmaceuticals have decided to discontinue further development of deligoparin.

September 16, 2002

Additional preliminary clinical data on IL13-PE38, NeoPharm's investigational tumor-targeting agent, confirmed the product's cytotoxic effects against malignant glioma tumor cells when infused prior to surgical resection of the tumor. This phase I/II trial, enrolling 18 subjects, involved a pre-resection convection-enhanced delivery of IL13-PE38 at various concentrations (0.25, 0.50, 1.0 or 2.0ug/ml). IL13-PE38 was reportedly well-tolerated with no evidence of dose-limiting toxicity.

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