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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Advanced Nonhematological Malignancies, Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Metastatic Breast Cancer, Head and Neck Squamous Cell Carcinoma, Gastroesophageal Adenocarcinoma

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Trial Information

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

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.

Inclusion Criteria:

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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:

Millennium Pharmaceuticals, Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

November 2013

Related Keywords:

  • Advanced Nonhematological Malignancies
  • Non-Small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Metastatic Breast Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Gastroesophageal Adenocarcinoma
  • SCLC
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Breast Neoplasms
  • Neoplasms
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Squamous Cell
  • Lung Neoplasms
  • Small Cell Lung Carcinoma
  • Head and Neck Neoplasms



MD Anderson Cancer CenterHouston, Texas  77030-4096
Huntsman Cancer InstituteSalt Lake City, Utah  84112
Medical Oncology Hematology, Stamford HospitalStamford, Connecticut  06902