Therapy Restricting Growth of Blood Vessels Failed in Mesothelioma Clinical Trial

Therapy Restricting Growth of Blood Vessels Failed in Mesothelioma Clinical Trial

An investigational cancer drug that restricts the growth of new blood vessels failed to improve disease in a Phase 2 clinical trial in patients with malignant pleural mesothelioma who progressed after chemotherapy.

A report from the trial (NCT01486368) showed that none of the 17 treated patients responded to the treatment, making researchers drop additional development plans.

The study, “A Phase II Study of PF-03446962 in Patients with Advanced Malignant Pleural Mesothelioma. CCTG Trial IND.207,” was led by researchers at Ottawa Hospital Cancer Centre and Ottawa Hospital Research Institute in Canada. The results were published in the Journal of Thoracic Oncology.

The drug candidate, called PF-03446962, is an antibody blocking ALK-1 (activin receptor-like kinase 1) — a factor that is crucial for blood vessel development. Preclinical research indicated that the compound had antitumor activity, and a Phase 1 trial (NCT00557856) of patients with advanced solid tumors of various types showed that the drug did reduce tumors also in humans.

Among the patients in the earlier Phase 1 clinical trial was a mesothelioma patient who experienced disease stabilization. The Phase 2 clinical trial recruited 17 mesothelioma patients who had undergone Platinol (cisplatin) chemotherapy. Four of the patients had also gone through radiotherapy.

Patients received between one and 12 cycles of treatment, which consisted of one intravenous infusion of PF-03446962 every 14 days. At the end of the 30-week study, none of the patients had a partial or complete response. Two patients had stable disease for 2.7 and 3.6 months, respectively.

The clinical trial, which was an open-label study without a control group, was divided into two stages. But the study was cut short after the first stage when an interim analysis revealed the lack of improvement among participants.

Side effects of the treatment were mostly mild, and the most common adverse events were nausea, headache, vomiting, high blood pressure, and protein leakage into the urine. There were also some cases of blood cell abnormalities. Still, the good safety profile did not motivate further studies.

Researchers noted that many other drug candidates that targeted blood vessel development failed when studied in a clinical trial. According to the research team, a possible explanation for the failures is that blocking one factor is not enough to prevent blood vessels from forming, as other molecular pathways may compensate for the loss.

Two authors reported financial ties to pharmaceutical companies.

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Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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