The Virtual Window: Clinical Trial Reports--June 2007

By Querida Anderson
Published: Wednesday, Jul 14, 2010

    CuraGen, TopoTarget Begin Study of HDAC Inhibitor Candidate as Combination Therapy for Soft Tissue Sarcomas

CuraGen Corporation and TopoTarget A/S initiated a Phase I/II evaluation of the efficacy and safety of intravenous belinostat (PXD101) in combination with doxorubicin for the treatment of soft tissue sarcomas (STS).

“The antitumor activity of belinostat we observed in preclinical models, combined with previously generated clinical results suggest there is activity of belinostat for the treatment of STS and leads us to believe that the combination of belinostat and doxorubicin could benefit patients with this disease,” commented Frank Armstrong, MD, President and Chief Executive Officer of CuraGen Corporation.

This open-label, multi¬center study will enroll 24 patients with solid tumors  for whom no standard therapy exists to define the maximal tolerated dose. The primary objectives for the trial are to determine the maximum tolerated dose and to assess the anti-tumor activity of belinostat and doxorubicin combination treatment. Secondary endpoints include the time to disease progression, overall survival, and duration of response. The pharmacokinetic profile and aspects of pharmacodynamic activity of belinostat will also be evaluated, the companies stated.

For the Phase II trial, the company plans to enroll an additional 20 to 40 STS pa¬tients who have not received prior chemotherapy.

Belinostat is a small molecule HDAC inhibitor being investigated in the treatment of solid and hematologic malignancies either as a single-agent or in combination with other active anti-cancer agents. It is currently in Phase II development for the treatment of T-cell lymphoma, ovarian cancer, and multiple myeloma and in Phase I for colorectal cancer and solid tumors.


    Ambrilia’s Therapeutic Peptide Shows Clinical Activity in Metastatic Prostate Cancer Patients

Ambrilia Biopharma Inc. reported that a Phase I/II trial indicates that the drug PCK3145 has clinical activity in metastatic prostate cancer patients.

The study was conducted at the Memorial Sloan Kettering Cancer Centre in New York City with 28 metastatic hormone refracto¬ry patients and led by co-investigators Drs. Susan Slovin and Howard Scher. The researchers found that this therapeutic peptide increased PSA doubling time (PSADT). The study also confirms down-regulation of MMP-9, a matrix metalloproteinase enzyme involved in facilitating tumor metastasis, and disease stabilization as assessed by time to radiographic progression in several patients, according to Ambrilia.

While the elevated MMP-9 plasma levels were reduced in most of the patients, 10 out of the 28 patients showed an increase in PSADT from 1.5 fold to 5 fold.

“We are greatly encouraged by these recent findings on the potential clinical benefits of PCK3145 in late stage prostate cancer patients”, said Stephen Sudovar, Ex-ecutive Chairman and Interim CEO of Ambrilia. “The safety profile together with the quantitative results on PSADT, MMP-9 as well as stabilization of the metastatic process, we believe, warrant further development of this product.”

PCK3145 is a synthetic 15-mer peptide that is derived from the natural sequence of amino acids of the prostate secretory protein (PSP94), one of three predominant proteins found in human seminal fluid. PSP94 expression in the prostate is down regulated in patients with advanced prostate cancer, and believed to be a survival mechanism for the cancer cells. The mechanism of action and receptor for PCK3145 suggests PCK3145 to be a signal transduction inhibitor with multiple ways to restrict disease development, Abrilia reports.


    Alchemia’s Precursory Evaluation of mCRC Study Presents Positive Efficacy Data

In a preliminary review, Alchemia Limited’s found that HyCAMP™ did not improve diarrhea incidence, its primary endpoint, in patients with metastatic colorectal cancer, compared to irinotecan. It did, however, increase median progression-free survival.

In the randomized trial, 80 patients who had previously failed treatment with 5-fluoro uracil were eligible to receive up to eight cycles of chemotherapy in the form of irinotecan or HyCAMP intravenously. The primary endpoint was the evaluation of incidence of late grade 3 or 4 diarrhea. Alchemia found a lower than expected incidence of diarrhea in the control arm. In regard to its secondary safety endpoints, the company saw no major differences in overall adverse events between the two treatment arms. The secondary efficacy endpoint was also met with median progression free survival for HyCAMP patients at 5.2 months compared to 2.4 months for the irinotecan arm. Patients on HyCAMP re¬ceived a median of six cycles of therapy compared to two for irinotecan alone.

Thus far, “the findings have far exceeded our expectations in that we did not expect to achieve a statistically significant improvement in efficacy from such a small number of patients” commented principal investigator Peter Gibbs.

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