Phase III Trial of Drug Custirsen in Prostate Cancer Produces Positive Interim Results

The gist: A clinical trial is currently testing a drug called custirsen in men with metastatic, castration-resistant prostate cancer (CRPC). The patients are receiving custirsen along with the chemotherapy drug cabazitaxel. The trial recently underwent a “futility analysis” to ensure it could continue as planned. Final results will be announced later this year or in 2016.

“OncoGenex Pharmaceuticals, Inc. (OGXI) today announced that the AFFINITY trial is continuing as planned based upon completion of the interim futility analysis and the recommendation of the Independent Data Monitoring Committee (IDMC).

“The Phase 3 AFFINITY trial is designed to evaluate a survival benefit for custirsen in combination with second-line cabazitaxel chemotherapy in 635 men with metastatic castrate-resistant prostate cancer (CRPC). AFFINITY is being conducted at 95 global clinical trial sites and final survival results are expected to be announced in late 2015 or early 2016.

” ‘While the results remain blinded to OncoGenex, we are very pleased that the AFFINITY trial has passed this interim futility analysis and we remain confident in the potential value of custirsen in treating cancer, particularly in patients who have advancing disease despite previous treatments,’ said Scott Cormack, President and CEO of OncoGenex.”


Men Treated with Enzalutamide Experienced a 17-Month Delay in the Time to Initiation of Chemotherapy Compared to Placebo

The gist: Prostate cancer patients in the EU can now be treated with the drug enzalutamide (aka XTANDI). The European Commission approved the drug for adult men with metastatic castration-resistant prostate cancer (nCRPC) who have no symptoms or mild symptoms after failed treatment with androgen deprivation therapy, and who are not yet eligible for chemotherapy treatment. In a clinical trial with volunteer patients, enzalutamide gave men 17 extra months before chemotherapy was needed.

“Astellas Pharma Europe Ltd. today announced that the European Commission (EC) has granted a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI).1 Enzalutamide is now approved in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.1

“ ‘Enzalutamide provides a viable treatment option for a broad population of men with mCRPC, regardless of age, or their readiness for chemotherapy, which provides a meaningful period of time during which men have their disease controlled without the need for chemotherapy’, said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. ‘The decision from the European Commission to approve enzalutamide, an effective and well tolerated alternative to chemotherapy, is a very important milestone for men with prostate cancer that has advanced.’

“The Marketing Authorisation approval is based on results from the pivotal phase III PREVAIL study which demonstrate that enzalutamide improves outcomes for men with advanced prostate cancer who have not received chemotherapy.2″


Future of Exelixis Cancer Drug Dims Further With Second Failed Prostate Cancer Study

The gist: A drug called cabozantinib doesn’t do any better than a steroid treatment when it comes to relieving bone pain in men with metastatic castration-resistant prostate cancer. That was the conclusion of a recent clinical trial that tested the drug in volunteer patients. The trial enrolled men who were suffering from moderate to severe pain despite optimized narcotic medication, and whose cancer had worsened after treatment with docetaxel as well as abiraterone and/or enzalutamide. Some of the men in the trial were treated with cabozantinib, and some with the steroid treatment mitoxantrone/prednisone.

“Exelixis (EXEL) announced Monday that treatment with cabozantinib failed to alleviate bone pain compared to a steroid control in men with advanced, metastatic prostate cancer. A negative outcome from the so-called COMET-2 prostate cancer study of cabozantinib was widely expected given the previously announced failure of the COMET-1 study in September. Still, Exelixis shares fell another 10% to $1.49 — an all-time low — on heightened concerns that ongoing cabozantinib studies in kidney and liver cancer may also prove disappointing.

“A few years ago, there was much optimism for cabozantinib based on phase II data showing the drug cleared bone lesions and reduced pain in advanced prostate cancer patients. Cancer that metastasizes, or spreads, to bones is a serious complication leading to fractures, increased pain and eventual death. While many cancer drugs can shrink or eliminate tumors in soft tissue, few if any had ever demonstrated an ability to clear up bone metastases.

“All too often, promising results from phase II studies don’t pan out when larger, confirmatory phase III studies are conducted. That’s exactly what happened to Exelixis. In the COMET-2 study, 15% of prostate cancer patients with moderate to severe bone pain despite use of narcotics responded to treatment with cabozantinib compared to 17% of patients treated with steroids. Clearly, this is not the results Exelixis had in mind three years ago when reporting on the phase II bone lesion/bone pain data in the phase II study.”


SOTIO Initiates US Part of VIABLE, a Global Phase III Clinical Trial for Prostate Cancer Immunotherapy Treatment with DCVAC/PCa

The gist: Researchers are testing a potential new prostate cancer treatment that boosts the immune system to fight prostate cancer. The immunotherapy is called DCVAC/PCa. It is made from a patient’s own immune system cells. It is being tested in a clinical trial in volunteer patients with metastatic castration‐resistant prostate cancer who have not yet received chemotherapy. Patients interested in enrolling can learn more at the trial website.

“The first US patient was enrolled into this Phase III global study in Rockville, MD. SOTIO is targeting to enroll around 250 US patients, collaborating with physicians from more than 80 US medical centers. Initial patients were also recently enrolled into the study in Italy, UK, the Netherlands and Slovakia. The VIABLE study plans to recruit patients through cooperation with medical centers in the United States, Canada and 25 European countries. SOTIO’s aim is to enroll approximately 1,170 prostate cancer patients globally. The first patient was enrolled into the VIABLE study in Hungary in May 2014.

“Niels Borgstein, Chief Medical Officer of SOTIO US commented: ‘Commencing the VIABLE study in the US is a crucial next step in our global clinical strategy to help develop a novel immunotherapy for the treatment of prostate cancer patients.’

“Professor Radek Špíšek, Chief Scientific Officer of SOTIO explained: ‘We believe that in order to be successful in treating advanced stages of prostate cancer it is essential to understand if cancer immunotherapy should be combined with existing treatment modalities, such as chemotherapy. In accordance with this strategy, we have designed a chemo-immunotherapy clinical trial that explores the combination of both standard of care chemotherapy including a novel dendritic cell based immunotherapy known as DCVAC/PCa.’ “


Galeterone Shows Activity in a Variant Form of Castration-Resistant Prostate Cancer

The gist: A drug called galeterone might help lower PSA levels in certain men with castration-resistant prostate cancer (CRPC). A clinical trial recently tested the treatment in volunteer patients.

“Results from a trial of the anti-cancer drug galeterone show that it is successful in lowering prostate-specific antigen (PSA) levels in men with a form of prostate cancer that is resistant to treatment with hormone therapy (castration-resistant prostate cancer or CRPC).

“Associate professor Mary-Ellen Taplin, of the Dana-Farber Cancer Institute, Boston, USA, will tell the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain, today (Wednesday) that galeterone was well tolerated by patients in the ARMOR2 trial, and also lowered PSA levels in a subset of men with CRPC that was resistant to other drugs that target the cancer, such as enzalutamide and abiraterone.

” ‘Recent data have shown that a variant of the androgen receptor called AR-V7, found in tumour cells circulating in the blood of patients with metastatic CRPC, predicted resistance to treatment with enzalutamide and abiraterone,’ she will say. ‘Indeed, we believe AR-V7 and other, related variants are a mechanism of resistance in this disease and patients who have them may have a poorer prognosis.’ ”


ArQule Announces Positive Top-Line Results of NIH-Sponsored Phase 2 Trial of Tivantinib in Prostate Cancer

The gist: A drug called tivantinib is showing some promise for treating patients with metastatic castration-resistant prostate cancer. Tivantinib was compared to a placebo in a clinical trial with volunteer patients. In the trial, patients who took tivantinib went for a longer time without their cancer worsening that patients who took the placebo.

“ArQule, Inc. (ARQL) today announced positive top-line results from a randomized, double-blind, placebo-controlled Phase 2 clinical trial of tivantinib as a single agent in metastatic prostate cancer. This trial (clinicaltrials.gov identifier NCT01519414) was conducted under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute’s Cancer Therapy Evaluation Program (CTEP) (‘A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of ARQ 197 (tivantinib) in Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer,’ NCI Protocol # 8986). The principal investigator was J. Paul Monk, M.D. of The Ohio State University, Arthur G. James Cancer Hospital and Solove Research Institute.

“In this trial, 78 patients were randomized 2 to 1 to receive either tivantinib as a single agent or placebo. During a pre-planned analysis, it was found that the trial met its primary endpoint of improving median progression-free survival (PFS) with tivantinib alone as compared to placebo. The results were highly statistically significant. Safety data were consistent with those observed in other trials of tivantinib.

“The results of the trial are the subject of ongoing analyses and will be submitted by the investigators for presentation at a future medical conference. As final data emerge from this trial, ArQule and its partner, Daiichi Sankyo Company, Limited, will discuss with the National Institutes of Health (NIH) the potential for additional trials in this indication.

“ ‘We are pleased that these significant findings from the NIH trial in prostate cancer add to the body of clinical evidence of the anti-cancer activity of tivantinib across multiple tumor types,’ said Paolo Pucci, chief executive officer of ArQule.”


Drugs Home in on Bone Metastases in Prostate Cancer


Bone metastases are common in patients with metastatic castration-resistant prostate cancer (CRPC). They are associated with increased risk of death due to a number of complications such as bone fractures, compression of the spinal cord, and pain. Radiation of the affected bone sites is used as a palliative measure to relieve pain. The U.S. Food and Drug Administration (FDA) has also approved certain drugs for treatment of bone metastases in CRPC including the following: Continue reading…


Sequencing Radium-223 and Docetaxel in Prostate Cancer

The gist: Scientists have found that the drug Xofigo (aka radium Ra223 dichloride) is “equally effective whether or not the patient has previously received chemotherapy with docetaxel.” Xofigo us used for men with metastatic castration-resistant prostate cancer (mCRPC).

“The novel radiopharmaceutical for prostate cancer, radium Ra223 dichloride (Xofigo), is equally effective whether or not the patient has previously received chemotherapy with docetaxel, a new analysis concludes.

“The product was approved last year for the treatment of metastatic castration-resistant prostate cancer (mCRPC) on the basis of results from the ALSYMCA study.

“Now, the ALSYMCA investigators report a prespecified analysis that shows that radium-223 is effective in these patients, regardless of previous docetaxel use. The report was published online October 17 in the Lancet Oncology.

“In an accompanying comment, Robert B. Den, MD, and W. Kevin Kelly, DO, from the Departments of Radiation and Medical Oncology, respectively, at Thomas Jefferson University in Philadelphia, say the new analysis shows that ‘men who have received previous docetaxel chemotherapy can be given radium-223 safely and its efficacy will be similar to patients who have not received previous docetaxel treatment.’

“But they also advocate caution. ‘The oncology community needs to proceed cautiously, since the ALSYMPCA trial was not able to identify the optimum sequence of administration of docetaxel and radium-233. Additionally, the trial was designed before the approval of enzalutamide and abiraterone acetate, so the clinical benefit of concomitant or sequential use of radium-223 with these drugs is unknown. Perhaps most intriguing would be the opportunity to integrate immunotherapy.’ “


Abiraterone Acetate/Prednisone in Metastatic Castration-Resistant Prostate Cancer: Final Analysis of Early-Access Protocol Study

The gist: In 2012, the U.S. Food and Drug Administration (FDA) approved a drug called Zytiga for the treatment of metastatic castration-resistant prostate cancer. It is prescribed along with the drug prednisone. Before the FDA’s approval, the Zytiga/prednisone combination was being tested in patients in a clinical trial. The trial was an “early-access” trial, meaning that it gave patients access to a very promising treatment that had not yet been approved. All patients involved had metastatic castration-resistant prostate cancer that had worsened after chemotherapy. Recently reported results from the trial showed no new safety concerns for the treatment.

“Abiraterone acetate (Zytiga) is approved for use in combination with prednisone in the treatment of metastatic castration-resistant prostate cancer. As reported by Sternberg et al in The Lancet Oncology, results of an open-label, early-access protocol trial initiated prior to approval indicated no new safety signals with abiraterone acetate plus prednisone given after progression on chemotherapy…

“The study, conducted in 23 countries, included 2,314 patients with metastatic castration-resistant prostate cancer progressing after taxane chemotherapy enrolled between November 2010 and September 2013. Patients received abiraterone acetate 1,000 mg/day and prednisone 5 mg twice a day in 28-day cycles until disease progression, development of sustained side effects, or approval and availability of abiraterone acetate in the country of residence…

“The investigators concluded: ‘No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients’ outcomes.’ ”