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Alisertib in Adults With Nonhematological Malignancies, Followed by Alisertib in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01045421
First received: January 8, 2010
Last updated: July 1, 2016
Last verified: July 2016
Results First Received: July 22, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Advanced Nonhematological Malignancies
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Metastatic Breast Cancer
Head and Neck Squamous Cell Carcinoma
Gastroesophageal Adenocarcinoma
Intervention: Drug: MLN8237 (Alisertib)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants took part in the study at 42 investigative sites in France, Poland, the Czech Republic, and the United States from 16 February 2010 to 25 April 2014.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with a historical diagnosis of relapsed or refractory advanced nonhematological malignancies were enrolled in 1 of the 2 stages, Phase 1 (lead-in alisertib dose escalation stage) and Phase 2 (efficacy and safety assessment stage for alisertib dose determined in Phase 1).

Reporting Groups
  Description
Phase 1: MLN8237 10 mg MLN8237 (alisertib) 10 milligram (mg), enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy during Phase 1 portion of the study.
Phase 1: MLN8237 20 mg MLN8237 (alisertib) 20 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy during Phase 1 portion of the study.
Phase 1: MLN8237 40 mg MLN8237 (alisertib) 40 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy during Phase 1 portion of the study.
Phase 1: MLN8237 50 mg MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy during Phase 1 portion of the study.
Phase 1: MLN8237 60 mg MLN8237 (alisertib) 60 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy during Phase 1 portion of the study.
Phase 1: MLN8237 50 mg- Pancreatic Cancer MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with pancreatic cancer during Phase 1 portion of the study.
Phase 2: MLN8237 50 mg- Breast Cancer MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with breast cancer during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- Gastric Cancer MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with gastric cancer during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- HNSCC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with head and neck squamous cell carcinoma (HNSCC) during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- NSCLC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with non-small cell lung cancer (NSCLC) during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- SCLC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with small cell lung cancer (SCLC) during Phase 2 portion of the study.

Participant Flow for 2 periods

Period 1:   Phase 1
    Phase 1: MLN8237 10 mg     Phase 1: MLN8237 20 mg     Phase 1: MLN8237 40 mg     Phase 1: MLN8237 50 mg     Phase 1: MLN8237 60 mg     Phase 1: MLN8237 50 mg- Pancreatic Cancer     Phase 2: MLN8237 50 mg- Breast Cancer     Phase 2: MLN8237 50 mg- Gastric Cancer     Phase 2: MLN8237 50 mg- HNSCC     Phase 2: MLN8237 50 mg- NSCLC     Phase 2: MLN8237 50 mg- SCLC  
STARTED     1     3     4     12     3     1     0     0     0     0     0  
COMPLETED     1     3     4     11     2     1     0     0     0     0     0  
NOT COMPLETED     0     0     0     1     1     0     0     0     0     0     0  
Progressive Disease                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 0                 1                 0                 0                 0                 0                 0                 0                 0  

Period 2:   Phase 2
    Phase 1: MLN8237 10 mg     Phase 1: MLN8237 20 mg     Phase 1: MLN8237 40 mg     Phase 1: MLN8237 50 mg     Phase 1: MLN8237 60 mg     Phase 1: MLN8237 50 mg- Pancreatic Cancer     Phase 2: MLN8237 50 mg- Breast Cancer     Phase 2: MLN8237 50 mg- Gastric Cancer     Phase 2: MLN8237 50 mg- HNSCC     Phase 2: MLN8237 50 mg- NSCLC     Phase 2: MLN8237 50 mg- SCLC  
STARTED     0     0     0     0     0     0     53     55     55     26     60  
COMPLETED     0     0     0     0     0     0     53     50     53     23     58  
NOT COMPLETED     0     0     0     0     0     0     0     5     2     3     2  
Progressive Disease                 0                 0                 0                 0                 0                 0                 0                 1                 1                 1                 1  
Death                 0                 0                 0                 0                 0                 0                 0                 1                 1                 2                 0  
Other                 0                 0                 0                 0                 0                 0                 0                 3                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Phase 1: MLN8237- All Participants MLN8237 (alisertib) 10, 20, 30, 40, 50, or 60 mg enteric-coated tablets, orally, twice daily, for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants enrolled in dose-escalation or pancreatic cancer cohort during Phase 1 portion of the study.
Phase 2: MLN8237 50 mg- Breast Cancer MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with breast cancer during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- Gastric Cancer MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with gastric cancer during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- HNSCC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with head and neck squamous cell carcinoma (HNSCC) during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- NSCLC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with non-small cell lung cancer (NSCLC) during Phase 2 portion of the study.
Phase 2: MLN8237 50 mg- SCLC MLN8237 (alisertib) 50 mg, enteric-coated tablets, orally, twice daily for 7 days followed by 14 days of rest period in 21-day treatment cycles for a maximum of 24 months, or until progressive disease, unacceptable treatment-related toxicity, or initiation of a different anticancer therapy in participants with small cell lung cancer (SCLC) during Phase 2 portion of the study.
Total Total of all reporting groups

Baseline Measures
    Phase 1: MLN8237- All Participants     Phase 2: MLN8237 50 mg- Breast Cancer     Phase 2: MLN8237 50 mg- Gastric Cancer     Phase 2: MLN8237 50 mg- HNSCC     Phase 2: MLN8237 50 mg- NSCLC     Phase 2: MLN8237 50 mg- SCLC     Total  
Number of Participants  
[units: participants]
  24     53     55     55     26     60     273  
Age, Customized  
[units: participants]
             
18-64 years     17     37     33     38     17     38     180  
65-84 years     7     16     21     17     9     22     92  
85 years and over     0     0     1     0     0     0     1  
Gender  
[units: participants]
             
Female     9     53     12     3     12     28     117  
Male     15     0     43     52     14     32     156  
Race/Ethnicity, Customized  
[units: participants]
             
Hispanic or Latino     3     4     2     1     1     1     12  
Not Hispanic or Latino     19     48     49     50     25     57     248  
Not reported     2     1     4     4     0     2     13  
Race/Ethnicity, Customized  
[units: participants]
             
White     18     49     51     53     22     56     249  
Black or African American     3     1     3     2     2     4     15  
Asian     2     1     0     0     1     0     4  
Chinese     0     0     0     0     1     0     1  
Other     0     1     0     0     0     0     1  
Not reported     1     1     1     0     0     0     3  
Region of Enrollment  
[units: participants]
             
Czech Republic     0     19     20     8     7     15     69  
France     0     10     8     11     3     8     40  
Poland     0     1     0     1     0     7     9  
United States     24     23     27     35     16     30     155  
Disease stage at study entry [1]
[units: participants]
             
IA     1     0     0     0     0     0     1  
II     0     0     0     1     0     0     1  
III     1     0     1     2     0     0     4  
IIIA     1     1     0     0     0     1     3  
IIIB     0     3     0     0     5     2     10  
IIIC     0     1     0     0     0     0     1  
IV     19     48     54     2     21     57     201  
IVA     1     0     0     23     0     0     24  
IVB     1     0     0     2     0     0     3  
IVC     0     0     0     25     0     0     25  
Eastern Cooperative Oncology Group (ECOG) performance status [2]
[units: participants]
             
0     4     23     21     17     7     13     85  
1     20     30     34     38     19     47     188  
[1] Assessment of disease stage for Medical History and Physical Examination at baseline were assessed according to the criteria set by the American Joint Committee on Cancer Tumor Staging version 7.0. The exact definition of a stage vary depending on the tumor type. Stage I cancers are the least advanced and often have a better prognosis. Higher stage cancers are often more advanced but in many cases can still be treated successfully.
[2] ECOG performance status assesses a participant's physical ability on a 6-point scale: 0=fully active, able to carry on all predisease activities without restriction; 1=restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2=ambulatory (>50% of waking hours), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hours; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Phase 1: Number of Participants With Dose-Limiting Toxicities (DLTs)   [ Time Frame: Phase 1: Cycle 1 Day 1 to Cycle 2 Day 21 ]

2.  Primary:   Phase 2: Percentage of Participants With Objective Response   [ Time Frame: Baseline until complete response or partial response, assessed every 2 cycles up to end of study (up to 50 cycles) ]

3.  Secondary:   Phase 2: Progression-free Survival (PFS)   [ Time Frame: Baseline until progressive disease, assessed every 2 cycles up to end of study (up to 50 cycles) ]

4.  Secondary:   Phase 2: Time to Disease Progression (TTP)   [ Time Frame: Baseline until disease progression, assessed every 2 cycles up to end of study (up to 50 cycles) ]

5.  Secondary:   Phase 2: Duration of Response (DOR)   [ Time Frame: Baseline up to Week 50 ]

6.  Secondary:   Phase 2: Number of Participants Reporting One or More Treatment-emergent Adverse Events and Serious Adverse Events   [ Time Frame: Baseline up to 30 days after the last dose of study drug ]

7.  Secondary:   Phase 1: Cmax- Maximum Observed Plasma Concentration for Alisertib   [ Time Frame: Days 1 and 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours post-dose ]

8.  Secondary:   Phase 1: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib   [ Time Frame: Days 1 and 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

9.  Secondary:   Phase 1: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib   [ Time Frame: Days 1 and 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

10.  Secondary:   Phase 1: Terminal Phase Elimination Half-life (T1/2) for Alisertib   [ Time Frame: Day 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

11.  Secondary:   Phase 1: Rac- Accumulation Ratio for Alisertib   [ Time Frame: Days 1 and 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

12.  Secondary:   Phase 1: Peak to Trough Ratio for Alisertib   [ Time Frame: Day 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

13.  Secondary:   Phase 1: Steady State Oral Clearance (CLss/F) for Alisertib   [ Time Frame: Day 7: predose, 30 minutes, 1, 2, 3, 4, 6, 8, and 12 hours postdose ]

14.  Secondary:   Phase 2: Relationship Between Clinical Response and Molecular Markers of Response   [ Time Frame: 12 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Director
Organization: Takeda
phone: +1-877-825-3327
e-mail: clinicaltrialregistry@tpna.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01045421     History of Changes
Other Study ID Numbers: C14007
2008-006981-27 ( EudraCT Number )
U1111-1171-0859 ( Registry Identifier: WHO )
Study First Received: January 8, 2010
Results First Received: July 22, 2015
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency