A Phase 1 Study of IXAZOMIB in Adult Patients With Advanced Nonhematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00830869
Recruitment Status : Completed
First Posted : January 28, 2009
Last Update Posted : June 24, 2014
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.

Brief Summary:
This is an open-label, multicenter, phase 1, dose escalation study of IXAZOMIB. The primary purpose of this study is to determine the safety profile, establish the maximum tolerated dose, and inform the phase 2 dose of IXAZOMIB administered intravenously in patients with nonhematologic malignancies.

Condition or disease Intervention/treatment Phase
Advanced Non-hematologic Malignancies Drug: IXAZOMIB Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 116 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Dose Escalation, Phase 1 Study of IXAZOMIB (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies
Study Start Date : March 2009
Actual Primary Completion Date : April 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1

All patients will receive IXAZOMIB IV injection on Days 1, 4, 8, and 11 of each treatment cycle followed by a rest period of 10 days.

The first stage of the study will be initiated at a starting dose of 0.125 mg/m2

Subsequent doses will increase until a maximum tolerated dose (MTD) is established.

Primary Outcome Measures :
  1. Dose limiting toxicities, adverse events, serious adverse events, assessments of clinical laboratory values, and vital sign measurements. [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. Plasma PK parameters [ Time Frame: 1 month ]
  2. Blood pharmacodynamic parameters [ Time Frame: 1 month ]
  3. Disease response based on the investigator's assessment [ Time Frame: 4 months ]
  4. Pharmacokinetics and pharmacodynamics in tumor tissue [ Time Frame: Day 1, Day 4 ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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

  1. Male or female patients 18 years or older
  2. Eastern Cooperative Oncology Group performance status 0-2
  3. A diagnosis of a nonhematologic malignancy for which standard treatment is no longer effective. In the expanded cohort, enrollment will be limited to patients with a diagnosis of NSCLC, head and neck cancer (squamous cell cancer), soft tissue sarcoma, or prostate cancer
  4. Suitable venous access PK and pharmacodynamic evaluations
  5. 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 to practice 2 effective methods of contraception or abstain from heterosexual intercourse.

  6. Voluntary written consent must be obtained
  7. Adequate clinical laboratory values during the screening period

Exclusion Criteria:

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

  1. Peripheral neuropathy ≥Grade 2
  2. Female patients who are lactating or have a positive serum pregnancy test during the screening period
  3. Major surgery within 14 days before the first dose of treatment
  4. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment
  5. Life-threatening illness unrelated to cancer
  6. Diarrhea >Grade 1 based on the NCI CTCAE categorization
  7. Systemic antineoplastic therapy / or radiotherapy within 21 days before the first dose of study treatment
  8. Systemic treatment with prohibited medications
  9. Patient has symptomatic brain metastasis
  10. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months
  11. QTc >470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period
  12. Known human immunodeficiency virus (HIV), hepatitis B and hepatitis C positive
  13. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  14. Treatment with any investigational products within 28 days before the first dose of study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00830869

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Washington
University of Washington- Seattle Cancer Care
Seattle, Washington, United States, 98109
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT00830869     History of Changes
Other Study ID Numbers: C16001
First Posted: January 28, 2009    Key Record Dates
Last Update Posted: June 24, 2014
Last Verified: June 2014

Additional relevant MeSH terms:
Proteasome Inhibitors
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glycine Agents
Neurotransmitter Agents
Physiological Effects of Drugs