Continuing evolution of opportunities in the management of mCRPC


Two media releases today give us additional insights into the future for the management of metastatic castration-resistant forms of prostate cancer (mCRPC) … and perhaps earlier stages of the disease too.

In one release, Exelixis says the company has approved an investigator-sponsored, Phase I dose escalation trial of cabozantinib + abiraterone in men with mCRPC who have progressive disease after one or two prior chemotherapy regimens. This study is being led by Dr. Chris Sweeney at the Dana-Farber Cancer Institute. Three Boston-based insitutions will assist in enrollment of patients to the study.

This study has two core parts. In the first part, patients will receive cabozantinib (at increasing doses of 20, 40, or 60 mg) in combination with 1000 mg of abiraterone daily and 5 mg of prednisone twice daily. Higher doses of cabozantinib may be used if there is a limited occurrence of toxicity caused by cabozantinib. The second part of the study will expand the use of doses shown to be safe and tolerable in the first part of the study.

Studies like this are going to be common as clinical research teams start to work out what combinations of innovative new drugs can be administered safely when given together … and whether they will also have higher effectiveness than the same drugs given alone but in sequence.

Details about this (relatively small) trial can be found in the media release, but have not as yet been posted to the ClinicalTrials.gov web site.

In the second release, BioSante Pharmaceuticals announced publication of data from a Phase I clinical study of its GVAX prostate cancer vaccine in combination with ipilimumab — again in men with mCRPC.This trial had a similar dose escalation structure to the trial just described. Fixed doses of GVAX Prostate were combined with escalating doses of ipilimumab (at 0.1, 0.3, 1.0, 3.0 and 5.0 mg/kg). The study enrolled 12 patients in three dose escalation cohorts and 16 patients in an expansion cohort, using ipilimumab at a dose of 3.0 mg/kg.

According to the media release from Biosante:

  • 53 percent of patients achieved at least stable disease.
  • 2 patients showed clear regression of metastases.
  • 23 percent of patients in the higher dose cohorts had confirmed partial PSA responses of > 50 percent from baseline.
  • The duration of disease stabilization ranged from 3 to 27 months
  • The median duration of PSA response was 12 months (range, 2 to 21 months).
  • There were no serious adverse events observed at the lower ipilimumab dose levels.
  • Administration of immunotherapy using GVAX Prostate was apparently well tolerated.

The data from this study (by Madan et al.) are published on line in The Lancet Oncology.

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