MLN8237 in Adults With Nonhematological Malignancies, Followed by MLN8237 in Lung, Breast, Head and Neck or Gastroesophageal Malignancies

This study has been completed.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc. Identifier:
First received: January 8, 2010
Last updated: March 3, 2015
Last verified: March 2015
This is an open-label, multicenter study with a phase 1 dose escalation portion and a 2-stage, phase 2 portion, investigating MLN8237 in patients with advanced nonhematological malignancies.

Condition Intervention Phase
Advanced Nonhematological Malignancies
Non-Small Cell Lung Cancer
Small Cell Lung Cancer
Metastatic Breast Cancer
Head and Neck Squamous Cell Carcinoma
Gastroesophageal Adenocarcinoma
Drug: MLN8237
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Study of MLN8237, an Aurora A Kinase Inhibitor, in Adult Patients With Nonhematological Malignancies, Followed by a Phase 2 of MLN8237 in Lung, Breast, Head and Neck, or Gastroesophageal Malignancies

Resource links provided by NLM:

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Phase 1: To assess the safety and tolerability of MLN8237, formulated as an enteric-coated tablet (ECT), on a 7-day dosing schedule for determining the recommended dose and schedule to be used in Phase 2 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Phase 2: To estimate the antitumor activity of MLN8237 as measured by overall response rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase 1: To characterize the pharmacokinetics of MLN8237, formulated as ECT, administered on a 7-day dosing schedule and to describe any antitumor activity that may be observed with treatment in patients with advanced nonhematological malignancies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase 2: To assess the relationship between clinical response and molecular markers of response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase 2: To assess additional measures of antitumor activity, including time to progression, progression-free survival and duration of response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Phase 2: To characterize the safety profile associated with MLN8237 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 273
Study Start Date: February 2010
Study Completion Date: January 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN8237
MLN8237 administered as an enteric-coated tablet (ECT)
Drug: MLN8237

Phase 1:

MLN8237 will be administered orally twice a day on a 7-day dosing schedule

Phase 2:

MLN8237 will be administered orally at the maximum tolerated dose determined in Phase 1 for 7-days followed by a minimum 14-day rest period.

Detailed Description:
Following the determination of the Recommended Phase 2 Dose (RP2D) and schedule (Phase 1), 20 response-evaluable patients in each of the 5 tumor indications will be enrolled (Phase 2-Stage 1). An interim analysis will determine which tumor indications will proceed to enroll an additional 25 patients (Phase 2-Stage 2) to further evaluate Overall Response Rate (ORR) and other secondary endpoints.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

  • 18 years or older
  • Histologically or cytologically confirmed metastatic and/or advanced solid tumor (Phase 1 only)
  • Phase 2 requires Non-small cell lung cancer (NSCLC); Small-cell lung cancer; Breast adenocarcinoma (female patients only); Squamous cell cancer of the head and neck (HNSCC); or Gastroesophageal adenocarcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
  • Voluntary written consent
  • Wiling to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures
  • Measurable disease (Phase 2 only)

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Female patients who are pregnant or lactating
  • Serious medical or psychiatric illness that could interfere with protocol completion
  • Receipt of more than 2 previous cytotoxic chemotherapeutic regimens (4 previous regimens for breast cancer). There is no limit on the number of prior noncytotoxic therapies
  • Prior treatment with Aurora A-targeted agents, including MLN8237
  • Prior treatment with high-dose chemotherapy
  • Prior allogeneic bone marrow or other organ transplant
  • Antineoplastic therapy, radiation therapy or any experimental therapy 21 days prior to first dose of MLN8237
  • Symptomatic brain metastasis
  • Radiotherapy to greater than 25% of bone marrow
  • Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected
  • Myocardial infarction within 6 months of enrollment
  • Uncontrolled cardiovascular condition
  • Major surgery within 14 days of first dose of MLN8237
  • Active infection requiring systemic therapy, or other serious infection
  • Inability to swallow oral medication
  • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
  • Patients requiring full systemic anticoagulation
  • History of uncontrolled sleep apnea syndrome
  • Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 and during the study
  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 identifier: NCT01045421

United States, Texas
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01045421     History of Changes
Other Study ID Numbers: C14007  2008-006981-27 
Study First Received: January 8, 2010
Last Updated: March 3, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Small Cell Lung Carcinoma
Head and Neck Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell processed this record on July 28, 2016