While we wait for the U.S. Food and Drug Administration (FDA) to decide whether to approve MDV3100 for the treatment of men with metastatic, castration-resistant prostate cancer (mCRPC) that has progressed after docetaxel-based chemotherapy, it is worth reviewing the significant range of other trials now in place to explore the potential utility of enzalutamide earlier (and perhaps even later) in the evolution of prostate cancer.
The following is a list of the ongoing, key trials of enzalutamide of which we are currently aware, together with a brief comment on the objective of each trial and a link to more information about each trial on the ClinicalTrials.gov web site:
- A new Phase II study, that should soon be enrolling patients, has been designed to investigate the safety and efficacy of enzalutamide in men with symptomatic, chemotherapy-naïve, mCRPC (i.e., men who are likely to have slightly more advanced disease than those in the PREVAIL trial referred to immediately below). We believe that this is the so-called ASPIRE trial that is referred to in a recent media release from Medivation, and is an an open-label study intended to evaluate the effects of enzalutamide in about 150 men who are theoretically eligible to receive chemotherapy but have chosen not to do this.
- The PREVAIL study, which was initiated some time ago, is a randomized, double-blind, multi-center, placebo-controlled Phase III clinical trial designed to see whether enzalutamide is better than a placebo in extending the survival of chemotherapy-naïve patients with mCRPC. According to media releases from Medivation and Astellas, this trial is now fully enrolled (which means that the information about this trial on the Clinical Trials.gov web site needs to be updated).
- The TERRAIN trial, which is being conducted primarily in Europe) is a randomized, double-blind, multi-center, Phase II trial designed to test the efficacy and safety of enzalutamide compared to bicalutamide (Casodex) in men with metastatic prostate cancer already controlled by either bilateral orchiectomy (surgical castration) or ongoing androgen deprivation therapy with an LHRH agonist or an LHRH antagonist at a stable dose; in other words, is enzalutamide better than a traditional antiandrogen when added to simple ADT?
- Enrollment has been completed in a 67-patient, open-label, single-arm, Phase II study of the safety and efficacy of enzalutamide with ADT-naïve prostate cancer.
- The Phase II STRIVE trial is a relatively new, randomized, double-blind, multi-center clinical study of the efficacy and safety study of enzalutamide (160 mg/day) compared to bicalutamide (50 mg/day) in men with recurrent prostate cancer who have serologic and/or radiographic disease progression subsequent to primary androgen deprivation therapy (ADT).
- A preliminary, 50-patient, randomized, Phase II trial is being carried out at four centers in the USA to investigate whether so-called “triplet therapy” (with enzalutamide + leuprolide + dutasteride) or enzalutamide alone can potentially improve post-surgical pathologic outcomes when administered as neoadjuvant therapy for 6 months prior to radical prostatectomy in men with localized prostate cancer.
There are also additional trials of enzalutamide being conducted in the treatment of very late stage disease:
- The expanded access trial (now being carried out at 28 centers in the USA) is now making enzalutamide available (prior to product approval) to eligible patients with mCRPC who have already been treated with docetaxel-based chemotherapy.
- A very small (18-patient) Phase I clinical trial is being conducted at two centers in the USA to explore whether enzalutamide can be used safely in combination with docetaxel-based chemotherapy in patients with advanced prostate cancer.
- A 60-patient, Phase II clinical trial being carried out exclusively at the M. D. Anderson Cancer Center in Houston is testing the safety and tolerability of enzalutamide + abiraterone acetate + prednisone in men with mCRPC in their bones.
Other trials that we might reasonably expect to see in the future (assuming that there are no setbacks to the development of enzalutamide for use in earlier stages of prostate cancer) include:
- A trial of enzalutamide + an LHRH agonist + radiation therapy in men with locally advanced prostate cancer (possibly as compared to an LHRH agonist + an antiandrogen + radiation therapy or as compared to just enzalutamide + radiation therapy)
- A trial of enzalutamide alone as second-line therapy for men with progressive disease after standard forms of first-line therapy like radiation or radical surgery
- A trial of enzalutamide alone in older men with intermediate-risk (and perhaps high-risk) disease who wish to avoid standard forms of first-line therapy like radiation or surgery but would rather “do something” as opposed to just waiting until standard ADT was required.
Of course, the key trial that many in the prostate cancer community already want to see is a head-to-head trial of enzalutamide alone vs. standard ADT (e.g., 2 weeks of antiandrogen therapy to prevent testosterone flare followed by continuous LHRH agonist therapy) in men who are either newly diagnosed with advanced prostate cancer or men who have progressive disease after prior therapy. Unfortunately, this is a trial that may not happen for a while, because failure in such a trial may represent a significant business risk for the developers and marketers of enzalutamide. On the other hand, success in such a trial would represent a massive business opportunity.