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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
First received: March 17, 2010
Last updated: January 6, 2016
Last verified: January 2016
This is an open-label, multicenter, Phase 1 study that will evaluate the safety and tolerability of MLN8237 given orally in combination with docetaxel as a treatment for advanced solid tumors to determine tolerable doses and schedules of MLN8237 and docetaxel to be evaluated in future Phase 2 studies.

Condition Intervention Phase
Advanced Solid Tumors
Adenocarcinoma of the Prostate
Drug: MLN8237 plus docetaxel
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Number of participants with adverse events and serious adverse events [ Time Frame: From enrollment through 30 days after the last dose of MLN8237 or docetaxel ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum plasma concentration, area under the plasma concentration vs time curve zero to the time of last measurement, area under the plasma concentration vs time curve zero to infinity, and half-life [ Time Frame: Cycle 1, Day 1;Cycle 2, Day 1 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of docetaxel when administered alone and coadministered with MLN8237

  • Maximum plasma concentration, time to maximum plasma concentration, and area under the plasma concentration vs time curve vs. over the dosing interval [ Time Frame: Days 1 and 7 of Cycle 1 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters of MLN8237

  • Best response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for patients with measurable disease and solid tumors other than castration-resistant prostate cancer [ Time Frame: At the end of every third treatment cycle and 30 days after last dose of MLN8237 or docetaxel if needed ] [ Designated as safety issue: No ]
  • Best response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or prostate specific antigen (PSA) response as applicable for patients with castration-resistant prostate cancer [ Time Frame: At the end of every third treatment (RECIST) or at every treatment cycle and 30 days after last dose of MLN8237 (PSA) ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN8237 + docetaxel Drug: MLN8237 plus docetaxel
Patients will receive a standard starting dose of docetaxel on Day 1 in combination with escalating doses of MLN8237 administered orally twice/day Days 1 through 7, repeated in 21-day cycles, except Cycle 2 when the MLN8237 dosing will be for maximum 5 days starting on Day 3 and continuing through Day 7


Ages Eligible for Study:   18 Years and older
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 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 study:

  • 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 MLN8237
  • 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 enrollment
    • 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 dexamethasone
  • Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate 80
  • Comorbid condition or unresolved toxicity that would preclude administration of docetaxel
  • 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01094288

United States, Indiana
Indianapolis, Indiana, United States
United States, Oregon
Portland, Oregon, United States
United States, Texas
San Antonio, Texas, United States
United States, Washington
Seattle, Washington, United States
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01094288     History of Changes
Other Study ID Numbers: C14009 
Study First Received: March 17, 2010
Last Updated: January 6, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators

ClinicalTrials.gov processed this record on May 25, 2016