A Phase II Trial of MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Weill Medical College of Cornell University
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT01799278
First received: February 22, 2013
Last updated: February 25, 2013
Last verified: February 2013
  Purpose

This study will evaluate the response rate of MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer (NEPC). MLN8237 is an orally administered Aurora kinase A inhibitor that has demonstrated broad antitumor activity in vitro and in vivo. In preclinical models, aurora kinase inhibition resulted in dramatic and preferential anti-tumor activity in NEPC with suppression of neuroendocrine marker expression.


Condition Intervention Phase
Small Cell Prostate Cancer
Neuroendocrine Prostate Cancer
Prostate Adenocarcinoma Plus > 50% Immunohistochemical Staining for Neuroendocrine Markers
Drug: MLN8237
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of the Aurora Kinase A Inhibitor MLN8237 in Patients With Metastatic Castrate Resistant and Neuroendocrine Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Response rate, as assessed by CT/MRI and bone scan, of treatment with MLN8237 for patients with neuroendocrine prostate cancer [ Time Frame: one year ] [ Designated as safety issue: No ]
    To evaluate the objective response rate of MLN8237 for patients with neuroendocrine prostate cancer with CT/MRI and bone scan every three cycles. Response will be based on Recist criteria 1.1.


Secondary Outcome Measures:
  • Progression-free survival in response to therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Patients will be followed for survival endpoints following completion of this study until death.

  • Overall survival in response to therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Patients will be followed for survival endpoints following completion of this study until death

  • Prostate-Specific Antigen (PSA) test response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    PSA to be followed every cycle to determine response.

  • Circulating Tumor Cell (CTC) response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression to determine response.


Estimated Enrollment: 10
Study Start Date: February 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All Patients
MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent.
Drug: MLN8237
MLN8237 will be administered orally. The study drug will be administered on an empty stomach with the patient remaining nothing by mouth (NPO), except for water and prescribed medications, for 2 hours before and 1 hour after each dose. Patients will be instructed to take each oral dose of MLN8237 with 8 ounces (1 cup, 240 mL) of water.
Other Name: Alisertib

Detailed Description:

This is a multi-institutional single-arm, open-label Phase 2 trial evaluating MLN8237 in patients with histologically confirmed or clinically suspected metastatic neuroendocrine prostate cancer. Subjects will be treated with MLN8237 at 50 mg twice daily for 7 days repeated every 21 days. Individual dose reductions will be made on the basis of the AEs observed. Therapy will continue until disease progression, unacceptable toxicity as a result of MLN8237, or withdrawal of patient consent. Patients will be followed with history, physical, and blood tests at each visit to monitor for toxicity. Response and progression will be evaluated by CT/MRI scan and bone scan after every 3 cycles and determined using RECIST v1.1. PSA and serum chromogranin A and NSE will be followed every cycle. CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression. Patients will be followed for survival endpoints following completion of this study until death.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Metastatic prostate carcinoma and at least one of the following:

    • Histologic diagnosis of small cell or neuroendocrine prostate cancer
    • Histologic diagnosis of prostate adenocarcinoma plus > 50% immunohistochemical staining for neuroendocrine markers (chromogranin, synaptophysin or neuron specific enolase)
    • Development of liver metastases in the absence of PSA progression as defined by PCWG2
  • Serum chromogranin A level >5 x upper limit of normal and/or serum neuron specific enolase (NSE) >2x upper limit of normal
  • Measurable disease by RECIST 1.1 with PCWG2 modifications
  • Patients with pure small cell neuroendocrine carcinoma on histology are not required to have received prior androgen deprivation therapy (ADT) or castrate levels of testosterone, but their testosterone state should be maintained for the duration of the study. Other patients are required to have surgical or ongoing chemical castration, with baseline testosterone level <50ng/dL.
  • Patients capable of fathering children must agree to use an effective method of contraception for the duration of the trial and should continue use for 4 months after last dose of study drug
  • Subjects must be able to take oral medication and to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration.
  • ANC > 1500/mm³, platelets > 100,000/mm³, Hgb > 9 g/dL. Values must be obtained without need for myeloid growth factor or platelet transfusion support within 14 days, however, erythrocyte growth factor is allowed as per published ASCO guidelines.
  • Total bilirubin ≤ ULN, SGOT (AST) and SGPT (ALT)< 1.5 x ULN. AST and/or ALT may be up to 5X ULN if with known liver metastases provided bilirubin is normal.
  • Adequate renal function as defined by serum creatinine ≤ 1.5 x ULN. If creatinine >1.5 x ULN, calculated or measured creatinine clearance must be ≥ 40 mL/minute (Cockcroft-Gault).
  • ECOG performance status 0-2
  • Estimated life expectancy > 3 months
  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  • Radiation therapy to 25% of bone marrow within 2 weeks of first dose
  • Residual > Grade 2 toxicity from prior treatment must have resolved with the exception of those explicitly described elsewhere in entry criteria
  • Known history of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease; requirement for supplemental oxygen.
  • Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids or H2 antagonists are allowed (see section 5.5)
  • Severe or uncontrolled systemic infection
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Other severe acute or chronic medical or psychiatric condition, including uncontrolled diabetes, malabsorption, resection of the pancreas or upper small bowel, requirement for pancreatic enzymes, any condition that would modify small bowel absorption of oral medications, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
  • Currently active other malignancy excluding controlled non-melanoma skin cancer. Patients are considered NOT to have "currently active" malignancy if they have completed any necessary therapy and are considered by their physician to be at less than 30% risk of relapse.
  • Treatment with the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine or phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01799278

Contacts
Contact: Renee Kahn, RN 212-746-1851 Rek9015@med.cornell.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Renne Kahn, RN    212-746-1851    rek9015@med.cornell.edu   
Contact: Alice Mercado, RN    212-746-5430    alm2051@med.cornell.edu   
Sponsors and Collaborators
Weill Medical College of Cornell University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Himisha Beltran, MD Weill Medical College of Cornell University
  More Information

No publications provided

Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01799278     History of Changes
Other Study ID Numbers: 1210013164
Study First Received: February 22, 2013
Last Updated: February 25, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Weill Medical College of Cornell University:
Metastatic prostate carcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 21, 2014