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Trial record 1 of 1 for:    C33001
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A Phase 1, Dose Escalation Study of MLN7243 in Adult Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02045095
First Posted: January 24, 2014
Last Update Posted: November 7, 2017
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.
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )
  Purpose
This is an open-label, multicenter, phase 1, dose escalation study with expansion cohorts that will evaluate the safety (establish the MTD and inform the RP2D), tolerability, PK, pharmacodynamics, and antitumor activity of MLN7243 in patients with advanced malignant solid tumors.

Condition Intervention Phase
Advanced Malignant Solid Tumors Drug: MLN7243 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study to Assess the Safety and Tolerability of MLN7243, an Inhibitor of Ubiquitin-Activating Enzyme (UAE), in Adult Patients With Advanced Solid Tumors

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

Primary Outcome Measures:
  • Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From signing of the informed consent form through 30 days after the last dose of study drug ]

Secondary Outcome Measures:
  • MLN7243 Pharmacokinetics [ Time Frame: Various time points during 21- or 28-day cycles ]
    Includes concentration at the end of infusion (Ceoi) and the area under the plasma-concentration curve from time zero to the last measurable concentration (AUClast).

  • Pharmacodynamic endpoints include determinations of changes in levels of pathway markers in tumor tissue following MLN7243 dosing. [ Time Frame: At screening and once in cycle 1 in a 21-or 28-day cycle ]
  • Measures of disease response including objective response rate using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Time Frame: At screening, at the end of every other cycle (21- or 28-day cycles), and at end of study up to 45 months ]
  • Duration of response using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [ Time Frame: At screening, at the end of every other cycle (21- or 28-day cycles), and at end of study up to 45 months ]

Estimated Enrollment: 119
Study Start Date: January 2014
Study Completion Date: November 2016
Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MLN7243 Drug: MLN7243

Dose escalation stage Schedule A: IV infusion on days 1, 4, 8, 11 for a 21-day treatment cycle Schedule B: IV infusion on days 1, 8, 15 for a 28-day treatment cycle

Dose expansion stage: MLN7243 will be administered following schedule A (twice-weekly, 21-day dosing) and/or B (once-weekly, 28-day dosing)


  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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. Patients must have a histologically confirmed diagnosis of an advanced, metastatic malignant solid tumor and must have failed or exhausted standard therapies or for which no standard therapy is available.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Patients with adequate hematologic and organ function
  5. All patients must have radiographically detectable tumors; however, measurable disease as defined by RECIST (version 1.1) is not required for participation in the dose escalation part of this study.
  6. Patients undergoing a biopsy procedure must have accessible lesions which are safe to biopsy.
  7. Recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior antineoplastic therapy, except alopecia.
  8. Female patients who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 4 months after the last dose of study drug, or agree to practice true abstinence.

    Male patients who agree to practice effective barrier contraception during the entire study treatment period through 4 months after the last dose of study drug or agree to practice true abstinence.

  9. Suitable venous access for the study-required blood sampling including PK sampling.

Exclusion Criteria

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

  1. Patients with clinically significant pre-existing cardiac impairment.
  2. Patients with known active CNS lesions are excluded. Systemic antineoplastic therapy or investigational agents within 21 days before the first dose of study drug.
  3. Radiotherapy within 14 days before the first dose of study drug is not allowed except for limited field radiotherapy for palliative bone pain.
  4. For patients where tumor biopsies are required or requested:

    • Any known coagulation abnormalities that would contraindicate the tumor biopsy procedure.
    • Ongoing therapy with any anticoagulant or antiplatelet agents (eg, aspirin, clopidogrel [Plavix®], heparin, or warfarin).
  5. Major surgery within 28 days before the first dose of MLN7243.
  6. Life-threatening illness unrelated to cancer.
  7. Any evidence of active infection or antibiotic therapy within 14 days before the first dose of MLN7243.
  8. Known human immunodeficiency virus (HIV) positivity or AIDS-related illness, hepatitis B virus, and hepatitis C virus.
  9. Patients whose weight is <40 kg.
  10. History of uncontrolled sleep apnea syndrome and other conditions that could result in excessive daytime sleepiness, such as severe chronic obstructive pulmonary disease.
  11. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.

For the exhaustive list, please contact the study central contact.

  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02045095


Locations
United States, Massachusetts
Boston, Massachusetts, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, South Carolina
Charleston, South Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02045095     History of Changes
Other Study ID Numbers: C33001
First Submitted: December 18, 2013
First Posted: January 24, 2014
Last Update Posted: November 7, 2017
Last Verified: February 2017