Early clinical data show galeterone safe, effective against prostate cancer

April 1, 2012

Patients with castration-resistant prostate cancer had limited side effects and in many cases a drop in prostate-specific antigen expression with galeterone (TOK-001), a small-molecule oral drug, according to phase I data presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

Castration-resistant prostate cancer (CRPC) is an advanced form of prostate cancer that occurs when the disease progresses after treatment with androgen deprivation therapy. Galeterone works against CRPC by blocking the , reducing levels of the ligand that binds to the receptor and degrading the androgen receptor protein.

"This drug has a novel combined mechanism of action," said co-lead researcher R. Bruce Montgomery, M.D., associate professor of at the University of Washington School of Medicine in Seattle, Wash. " are sly and mutate to get around drugs. The fact that this drug hits the prostate cancer cell in three different ways may help prevent resistance. It is a well-tolerated drug that could potentially be more effective than drugs we have now."

In the ARMOR1 study, Montgomery and colleagues assigned 49 patients with CRPC to one of eight dose regimens in single or split oral escalation doses of 650 mg, 975 mg, 1,300 mg, 1,950 mg or 2,600 mg every day for 12 weeks. None of the patients had received chemotherapy for their .

Researchers reported that no patients reached a maximum tolerated dose. Most side effects were minor and included fatigue, nausea and diarrhea. Researchers observed transient, nonserious elevated liver function tests in 15 patients, many of whom were asymptomatic. Eleven of these patients temporarily stopped galeterone treatment, and six returned to treatment with no recurring elevations. One serious complication occurred involving rhabdomyolysis in the setting of simvastatin therapy and underlying renal insufficiency.

In early efficacy tests, 49 percent of patients had prostate-specific antigen (PSA) reductions of 30 percent or more; 11 of these patients had reductions of 50 percent or more. In addition, CT scans revealed reduction in tumor size for some patients.

"Because the androgen receptor controls PSA expression, improved PSA response shows that the drug is getting to the target," said Montgomery. "For the majority of patients, to reduce their PSAs by 30 percent or more is quite good in a phase I dose-finding trial."

Researchers will investigate long-term safety and an assessment of efficacy in a phase II study that Tokai Pharmaceuticals has planned for the second half of 2012.

Explore further: Targeted cancer therapy kills prostate tumor cells

More information: ARMOR1: Safety of galeterone (TOK-001) in a phase I clinical trial in chemotherapy naïve patients with castration resistant prostate cancer (CRPC).

Introduction: Galeterone is an orally available, semi-synthetic steroid analog for the treatment of castration-resistant prostate cancer (CRPC) that inhibits prostate cancer growth through a triple mechanism-of-action by: a) inhibiting CYP17 lyase activity; b) binding to and inhibiting the androgen receptor; and, c) degrading androgen receptor protein. ARMOR1, a phase I dose escalation study in men with chemotherapy naive CPRC, evaluated the safety of galeterone. Preliminary efficacy was also assessed by measuring changes in prostate-specific antigen (PSA) levels and tumor response.
Methods: Forty-nine men with metastatic and non-metastatic chemotherapy-naïve CRPC were enrolled in the ARMOR1 study. Patients were enrolled with confirmed adenocarcinoma of the prostate and disease progression during androgen ablation therapy. Patients ranged in age from 48 to 93 years old and had ECOG status of 0 or 1. Patients were randomized to one of eight dose escalation cohorts receiving galeterone capsules in single or split oral doses of 650, 975, 1300, 1950, or 2600mg daily for 12 weeks. After 12 weeks, eligible patients could continue treatment in an extension phase.
Results: Maximum tolerated dose was not reached. The frequency of patients with Grade 1 and Grade 2 adverse events (AEs) reported by body system was 58% and 30% respectively. The most commonly reported AEs by patient were fatigue (36.7%), aspartate aminotransferase (AST) increase (32.7%), alanine aminotransferase (ALT) increase (30.6%), nausea (28.6%), diarrhea (26.5%), and pruritus (24.5%). Grade 2 and 3, transient, non-serious, elevations of liver function tests (LFTs) were observed in 15 patients with the majority being completely asymptomatic. Of these patients, 11 underwent drug interruptions, and 6 of 7 patients were successfully rechallenged and returned to treatment with no recurring Grade 3 or higher LFT elevations. Nine SAEs were reported in the study, with all except one unrelated to galeterone. The single, related, grade 4 case involved rhabdomyolysis that occurred in the setting of simvastatin therapy (40 mg qd) and underlying renal insufficiency. No events of adrenal mineralocorticoid excess (AME) were observed in this study. PSA reductions were seen in a majority of patients; 24 (49%) patients had >30% maximal PSA reductions, including 11 patients (22%) with >50% maximal PSA reductions.
Conclusion: Galeterone was well tolerated, with all cohorts showing an acceptable safety profile. Galeterone also demonstrated activity in patients with CRPC. Additional long term safety will be further explored in a planned phase II study.

Related Stories

Targeted cancer therapy kills prostate tumor cells

June 6, 2011
A new targeted therapy for prostate cancer halts tumor growth in animals with advanced prostate cancer that is resistant to hormone therapy, a new study finds. The results will be presented Saturday at The Endocrine Society's ...

Study identifies new prostate cancer drug target

February 6, 2012
Research led by Wanguo Liu, PhD, Associate Professor of Genetics at LSU Health Sciences Center New Orleans, has identified a new protein critical to the development and growth of prostate cancer. The findings are published ...

Curry spice component may help slow prostate tumor growth

February 10, 2012
Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson's ...

Recommended for you

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.