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A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumors, Adenocarcinoma of the Prostate

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Trial Information

A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen

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 advanced tumors and candidates for
docetaxel treatment

- Measurable or evaluable disease is required. Patients must have clinical evidence of
progressive disease or persistent disease

- Patients with castration-resistant prostate cancer (CRPC) are required to have

- Pathologically confirmed adenocarcinoma of the prostate

- Evidence of metastatic disease on bone scan or other imaging. Patients with PSA
elevation as the only manifestation of disease are not eligible.

- Progressive disease after at least 1 hormonal treatment with documented
testosterone levels less than 50 ng/dl

- Concurrent use of an agent for testosterone suppression (e.g., LHRH agonist) is
required if the patient has not been surgically castrated

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Recovered to less than or equal to Grade 1 toxicity (CTCAE), to patient's baseline
status (except alopecia) or deemed irreversible from the effects of prior cancer
therapy and must have evidence of progressive or persistent disease

- Adequate bone marrow, liver and renal function

- Any use of opiates must be stable for at least 2 weeks prior to study entry

- Female patients who are postmenopausal for at least 1 year OR are surgically sterile
OR if of childbearing potential, agree to practice 2 effective methods of
contraception at the same time

- Male patients who agree to practice effective barrier contraception during the entire
study and through 6 months after the last dose of study drug OR agree to abstain from
heterosexual intercourse

- Voluntary written consent

- Willing to comply with scheduled visits, treatment plan, laboratory tests and other
trial procedures

- Suitable venous access for blood sampling

Exclusion Criteria:

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

- Female patients who are lactating or pregnant

- Antineoplastic therapy or any experimental therapy within 21 days before the first
dose of MLN8237

- Prior or current investigational therapies within 4 weeks before the first dose of

- Concurrent investigational treatment of treatment with any investigational products
within 28 days before the first dose of MLN8237

- Radiotherapy to greater than 40% of bone marrow or any radiotherapy (except
localized, small field radiation) within 4 weeks prior to enrollment, unless reviewed
and approved by the medical monitor

- Nitrosoureas or mitomycin-C within 6 weeks before the first dose of MLN8237.

- Autologous stem cell transplant within 3 months before the first dose of MLN8237, or
prior allogeneic stem cell transplant at any time.

- Use of enzyme-inducing antiepileptic drugs such as phenytoin, carbamazepine or
phenobarbital, or rifampin, rifabutin, rifapentine or St. John's wort within 14 days
prior to the first dose of MLN8237

- For CRPC patients:

- Radiotherapy or antiandrogen therapy for prostate cancer within 4 weeks prior to

- Prior treatment with antineoplastic chemotherapy or radioisotopes for advanced
prostate cancer

- Use of products known to affect PSA levels within 4 weeks of enrollment

- Major surgery within 4 weeks of study enrollment

- Uncontrolled high blood pressure

- Patients with abnormal gastric or bowel function or who require continuous treatment
with antacids or proton pump inhibitors

- Patients receiving chronic steroid therapy other than the following: low dose steroid
for the control of nausea and vomiting, topical steroid, inhaled steroid or use of

- Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate

- Comorbid condition or unresolved toxicity that would preclude administration of

- Prior history of Grade 2 or greater neurotoxicity or any toxicity that has not
resolved to Grade 1 or below

- Symptomatic brain or other CNS metastasis

- 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

- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
hepatitis C

- Patients requiring full systemic anticoagulation

- Prior allogeneic bone marrow or other organ transplant

- Active infection requiring systemic therapy within 14 days preceding first dose, or
other serious infection

- History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months

- Serious medical or psychiatric illness that could interfere with protocol completion

- Inability to swallow oral medication

- Prior treatment with more than 3 myelosuppressive cytotoxic chemotherapy regimens

- Prior treatment with more than 1 prior taxane-containing regimen

Type of Study:


Study Design:

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

Outcome Measure:

Number of participants with adverse events and serious adverse events

Outcome Time Frame:

From enrollment through 30 days after the last dose of MLN8237 or docetaxel

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:

September 2010

Completion Date:

May 2014

Related Keywords:

  • Advanced Solid Tumors
  • Adenocarcinoma of the Prostate
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms
  • Neoplasms



University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811