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A Phase 1 Study of MLN9708 in Adult Patients With Advanced Nonhematologic Malignancies
This study is currently recruiting participants.
Verified by Millennium Pharmaceuticals, Inc., March 2009
First Received: January 26, 2009   Last Updated: March 26, 2009   History of Changes
Sponsored by: Millennium Pharmaceuticals, Inc.
Information provided by: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00830869
  Purpose

This is an open-label, multicenter, phase 1, dose escalation study of MLN9708. The primary purpose of this study is to determine the safety profile, establish the maximum tolerated dose, and inform the phase 2 dose of MLN9708 administered intravenously in patients with nonhematologic malignancies.


Condition Intervention Phase
Advanced Non-Hematologic Malignancies
Drug: MLN9708
Phase I

MedlinePlus related topics: Cancer
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment
Official Title: An Open-Label, Dose Escalation, Phase 1 Study of MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies

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

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

Secondary Outcome Measures:
  • Plasma PK parameters [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Blood pharmacodynamic parameters [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Disease response based on the investigator's assessment [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: March 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
MLN9708
Drug: MLN9708

All patients will receive MLN9708 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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 blood and chemistry values during the screening period:

    • Absolute neutrophil count (ANC) ≥1,500/mm3; platelet count ≥100,000/mm3
    • Total bilirubin must be ≤1.5 × the upper limit of the normal range upper limit of normal (ULN).
    • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), must be ≤2.5 × the upper limit of normal (ULN). AST and ALT may be elevated up to 5 times the upper limit of normal if their elevation can be reasonably ascribed to the presence of metastatic disease.
    • Calculated creatinine clearance ≥30 mL/minute

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00830869

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-866-835-2233 medical@mlnm.com

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Recruiting
Tampa, Florida, United States, 33612-9497
United States, Tennessee
Sarah Cannon Cancer Center Recruiting
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc. ( Clinical Research Monitor )
Study ID Numbers: C16001
Study First Received: January 26, 2009
Last Updated: March 26, 2009
ClinicalTrials.gov Identifier: NCT00830869     History of Changes
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on May 06, 2009