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

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ClinicalTrials.gov Identifier: NCT01799278
Recruitment Status : Completed
First Posted : February 26, 2013
Results First Posted : November 29, 2017
Last Update Posted : January 23, 2018
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Small Cell Prostate Cancer
Neuroendocrine Prostate Cancer
Prostate Adenocarcinoma Plus > 50% Immunohistochemical Staining for Neuroendocrine Markers
Intervention Drug: MLN8237
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Patients
Hide Arm/Group Description MLN8237 at 50 mg twice daily for 7 days repeated every 21 days.
Period Title: Overall Study
Started 60
Completed 60
Not Completed 0
Arm/Group Title All Patients
Hide Arm/Group Description This is a 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
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 60 participants
67
(45 to 87)
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female 0
Male 60
[1]
Measure Description: All subjects are Male
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Hispanic or Latino
4
   6.7%
Not Hispanic or Latino
50
  83.3%
Unknown or Not Reported
6
  10.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   3.3%
White
49
  81.7%
More than one race
0
   0.0%
Unknown or Not Reported
8
  13.3%
1.Primary Outcome
Title Response Rate, as Assessed by CT/MRI and Bone Scan, of Treatment With MLN8237 for Patients With Neuroendocrine Prostate Cancer
Hide Description Evaluated per RECIST 1.1 guidelines: Complete response (CR) is defined as complete disappearance of all measurable and evaluable lesions by physical examination or imaging studies and normalization of PSA with no appearance of new lesions for > 1 month. Partial response (PR) is defined as a 30% 56 or greater reduction in the sum longest unidimensional diameter of all measurable lesions. There may be no new lesions. Stable Disease (SD) is characterized by patients who do not meet the criteria of PR and who are without signs of progressive disease for at least 1 month. Disease Progression (DP) is defined as a greater than 20% increase in the sum longest unidimensional diameters of the indicator lesions or the appearance of new lesions. Bone scan progression (evaluable disease only) is defined by PCWG2 criteria. Per consensus guidelines in CRPC, to be considered measurable, lymph nodes need to be at least 2 cm in greatest dimension and 1.5 cm in short axis.
Time Frame one year
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Patients
Hide Arm/Group Description:
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. 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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: participants
18
2.Secondary Outcome
Title Progression-free Survival in Response to Therapy
Hide Description Patients will be followed for survival endpoints following completion of this study until death.
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title ALL SUBJECTS
Hide Arm/Group Description:
A 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.
Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
Castration-Resistant Prostate Cancer
2.2
(2.0 to 2.6)
Neuroendocrine Prostate Cancer
2.3
(2.0 to 2.6)
Castration-Resistant ProstateCancer-Adenocarcinoma
2.0
(2.0 to 2.6)
3.Secondary Outcome
Title Overall Survival in Response to Therapy
Hide Description Patients will be followed for survival endpoints following completion of this study until death
Time Frame 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Patients
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 60
Median (95% Confidence Interval)
Unit of Measure: months
9.5
(7.4 to 13.0)
4.Secondary Outcome
Title Prostate-Specific Antigen (PSA) Test Response Rate
Hide Description PSA to be followed every cycle to determine response.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this outcome.
Arm/Group Title All Patients
Hide Arm/Group Description:
MLN8237 at 50 mg twice daily for 7 days repeated every 21 days.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Circulating Tumor Cell (CTC) Response
Hide Description CTC counts by CellSearch will be performed at baseline, at 4-6 weeks, and upon progression to determine response.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for this outcome.
Arm/Group Title All Patients
Hide Arm/Group Description:
This is a 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
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame AEs which are serious must be reported to WCMC from first dose of MLN8237 up to and including 30 days after administration of the last dose of MLN8237. When possible, signs and symptoms indicating a common underlying pathology should be noted as one comprehensive event.
Adverse Event Reporting Description An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a product whether or not it is related to the medicinal product. For this protocol an abnormal laboratory value will not be assessed as an AE unless that value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline.
 
Arm/Group Title All Patients
Hide Arm/Group Description

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.

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.

All-Cause Mortality
All Patients
Affected / at Risk (%)
Total   48/60 (80.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
All Patients
Affected / at Risk (%)
Total   23/60 (38.33%) 
Blood and lymphatic system disorders   
Neutropenia * 1  1/60 (1.67%) 
Febrile neutropenia * 1  4/60 (6.67%) 
Anemia * 1  4/60 (6.67%) 
Thrombocytopenia * 1  3/60 (5.00%) 
General disorders   
Fatigue * 1  6/60 (10.00%) 
Pain * 1  1/60 (1.67%) 
Immune system disorders   
Rash * 1  1/60 (1.67%) 
Metabolism and nutrition disorders   
Electrolyte abnormalities * 1  4/60 (6.67%) 
Dehydration * 1  3/60 (5.00%) 
Nervous system disorders   
Neuropathy * 1  1/60 (1.67%) 
Syncope * 1  1/60 (1.67%) 
Intracranial hemorrhage * 1  1/60 (1.67%) 
Renal and urinary disorders   
Infection (urinary tract, skin) * 1  3/60 (5.00%) 
Hematuria * 1  1/60 (1.67%) 
Acute kidney injury * 1  1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders   
dyspnea * 1  2/60 (3.33%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Patients
Affected / at Risk (%)
Total   60/60 (100.00%) 
Ear and labyrinth disorders   
Edema * 1  11/60 (18.33%) 
Dizziness * 1  8/60 (13.33%) 
Gastrointestinal disorders   
Anorexia * 1  27/60 (45.00%) 
nausea * 1  23/60 (38.33%) 
Vomiting * 1  11/60 (18.33%) 
Gastroesophageal reflux disease * 1  7/60 (11.67%) 
Mucositis oral * 1  6/60 (10.00%) 
General disorders   
Fatigue * 1  47/60 (78.33%) 
pain * 1  23/60 (38.33%) 
Fever * 1  7/60 (11.67%) 
Peripheral sensory neuropathy * 1  7/60 (11.67%) 
Immune system disorders   
Dyspnea * 1  16/60 (26.67%) 
Investigations   
Creatinine increased * 1  7/60 (11.67%) 
Metabolism and nutrition disorders   
Dehydration * 1  7/60 (11.67%) 
Psychiatric disorders   
Depression * 1  13/60 (21.67%) 
Renal and urinary disorders   
Urinary frequency * 1  12/60 (20.00%) 
Hematuria * 1  10/60 (16.67%) 
Urinary incontinence * 1  8/60 (13.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  11/60 (18.33%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  16/60 (26.67%) 
Vascular disorders   
Hot flashes * 1  8/60 (13.33%) 
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Himisha Beltran
Organization: Weill Cornell Medical College
Phone: (646) 962-2072
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT01799278     History of Changes
Other Study ID Numbers: 1210013164
First Submitted: February 22, 2013
First Posted: February 26, 2013
Results First Submitted: October 30, 2017
Results First Posted: November 29, 2017
Last Update Posted: January 23, 2018