New Weill Cornell Clinical Trial: Aurora Kinase A Inhibitor MLN8237 in Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer

The Urological Oncology Program has recently opened a new, investigator-initiated clinical trial for for men with metastatic castrate resistant prostate cancer and neuroendocrine prostate cancer.  The principal investigator is Dr. Himisha Beltran.

For more information about the study, please call Renee Khan, RN at (212) 746-1851, e-mail Renee at rek9015@med.cornell.edu.

Key Eligibility
  • Men age 18 and older
  • Metastatic neuroendocrine prostate cancer
  • Have had surgical or ongoing chemical castration (men with pure small cell neuroendocrine prostate cancer are not required to have received androgen deprivation therapy or castrate levels of testosterone)
  • Detailed eligibility reviewed when you contact the study team
Study Details

The purpose of the study is to evaluate how well men with neuroendocrine prostate cancer respond to treatment with the experimental drug MLN8237.

MLN8237 (also called alisertib) is a pill taken by mouth. It has been developed to interfere with cell division, which is required for cancer cell growth. Aurora A kinase is an enzyme that may have a role in the progression of prostate cancer to neuroendocrine prostate cancer, which tends to behave aggressively and not respond well to most other therapies used for advanced prostate cancer. MLN8237 works by blocking Aurora A kinase. This may interfere with dividing cells, thereby slowing the growth of cancer and killing cancer cells.

All study participants will receive MLN8237; there is no placebo used in this study.  Participants will take MLN8237 in 21-day cycles:

  •  MLN8237 twice a day for 7 days in a row; after the 7 days of treatment, will not take it again for 2 weeks and then restart the cycle again

Study participants will continue with MLN8237 therapy as long as they are responding to treatment and not experiencing unacceptable side effects.

Department of Defense Highlights Weill Cornell Prostate Cancer Research

tagawa_team_smWeill Cornell’s Dr. Scott Tagawa and his research team are featured on the  Department of Defense’s Congressionally Directed Medical Research Programs (CDMRP) website as one of the “2013 Prostate Cancer Research Highlights.” The article focuses on Dr. Tagawa’s research of an antibody called J591. J591 specifically recognizes prostate specific membrane antigen (PSMA), allowing prostate cancer cells to be targeted to be specifically targeted. Dr. Tagawa collaborated with Weill Cornell’s Dr. Neil Bander and his team to develop J591.

J591 was attached to a tiny radioactive particle called 177Lu. 177Lu-J591 seeks out prostate cancer cells and delivers a lethal dose of radiation to the areas of cancer, but not to normal areas. The researchers have been utilizing J591 in menwith metastatic prostate cancer for over a decade, with success in targeting metastatic tumors and decreases in PSA, tumor size, and pain symptoms.

The Defense Department’s Prostate Cancer Research Program Clinical Trial Award allowed the researchers to expand clinical testing of J591 through a multi-site, phase 2 clinical trial combining hormonal therapy with targeted J591 radiation. The researchers plan to initiate a Phase 3 trial of the radiolabeled J591.

Click here to read the CDMRP article.

Weill Cornell’s Dr. Scott Tagawa Presents Positive Results of ATL101 at ASCO

ATLAB Pharma SAS announced that positive results of a phase II study of ATL101 (Lutetium-177 anti-PSMA antibody) on 47 patients with progressive metastatic castrate-resistant prostate cancer (mCRPC) have been presented at the ASCO 2013 Genitourinary cancer meeting.

Weill Cornell’s Dr. Scott Tagawa presented the results and the survival update. The study was performed at Weill Cornell Medical College/NewYork-Presbyterian Hospital and Memorial Sloan-Kettering Cancer Center.

ATL101 is a new targeted radiotherapy experimental drug for treating prostate cancer. ATL101 combines the humanized J591 monoclonal antibody targeting prostate-specific membrane antigen (PSMA) plus the Lutetium-177 radioisotope, creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.

In the study, ATL101 was administered as a single intravenous injection at 2 radioactivity dose levels, 65 or 70 mCi/m^2, in two consecutive cohorts of patients with metastatic castration-resistant prostate cancer (mCRPC). A third cohort was added at the 70mCi/m^2 dose. All patients had failed up to 4 hormonal therapies, and 55% of the patients had failed at least one docetaxel-containing chemotherapy regimen.

The results suggested a statistically significant relationship between injected dose and antitumor activity. The percentage of patients achieving PSA decline over 30% (30% PSA decline) increased from 13 % in Cohort (1) to 47 % in Cohort (2). The expansion Cohort 3 confirmed the rates of 30% PSA decline at 47% of patients. A treatment effect on the circulating tumor cells (CTC) count was also observed. Moreover, median overall survival (OS) significantly increased with the injected dose of radioactivity from 11.9 months in cohort (1) to 21.8 months in cohorts 2 and 3. The treatment was well tolerated with predictable, transient, and manageable dose-related changes in blood cell counts. Patients experienced no serious symptomatic side effects.

ATL101 is actively studied at Weill-Cornell Medical College/New York-Presbyterian Hospital in Phase I trials evaluating fractionated administration and combination with docetaxel. In addition, a randomized, multi-centre Phase II trial of ATL-101 in patients who have relapsed following surgery and/or radiation therapy and hormonal therapy but who do not yet have demonstrable metastatic disease is ongoing at several clinical sites in the USA. Click here to view the Phase II trial at clinicaltrials.gov.