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Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors

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.
 
ClinicalTrials.gov Identifier: NCT01862328
Recruitment Status : Completed
First Posted : May 24, 2013
Last Update Posted : June 11, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
This is an open-label, multicenter, phase 1b, dose escalation study of MLN4924 plus docetaxel, gemcitabine or combination of carboplatin and paclitaxel in adult patients with solid tumors.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: MLN4924 and Docetaxel Drug: MLN4924 + Paclitaxel + Carboplatin (Arm 2) Drug: MLN4924 + Gemcitabine (Arm 3) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors
Actual Study Start Date : July 1, 2013
Actual Primary Completion Date : February 15, 2016
Actual Study Completion Date : May 21, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MLN4924 and Docetaxel (Arm 1) Drug: MLN4924 and Docetaxel

MLN4924 (IV) and Docetaxel (IV) in patients to determine maximum tolerated dose (MTD) on a 21-day cycle:

  • MLN4924 on Days 1,3,5 of each cycle
  • Docetaxel on Day 1 of each cycle
  • On Day 1 of each cycle, patients receive both agents

Experimental: MLN4924 + Paclitaxel + Carboplatin (Arm 2) Drug: MLN4924 + Paclitaxel + Carboplatin (Arm 2)

MLN4924 (IV) Paclitaxel (IV), and Carboplatin (IV) in patients to determine maximum tolerated dose (MTD) on a 21-day cycle:

  • MLN4924 on Days 1,3,5 of each cycle
  • Paclitaxel on Day 1 of each cycle
  • Carboplatin on Day 1 of each cycle
  • On Day 1 of each cycle, patients receive all 3 agents

Experimental: MLN4924 + Gemcitabine (Arm 3) Drug: MLN4924 + Gemcitabine (Arm 3)

MLN4924 (IV) and Gemcitabine (IV) in patients to determine maximum tolerated dose (MTD) on a 28-day cycle:

•MLN4924 and Gemcitabine on Days 1,8,15 of each cycle





Primary Outcome Measures :
  1. Number of Adverse events [ Time Frame: Recorded from the first dose of any study drug through 30 days (+ 10 days) after the last dose of study drug ]

Secondary Outcome Measures :
  1. MLN4924 plasma concentration time data for population PK analysis [ Time Frame: Depending on study arm and whether the patient is in dose escalation/MTD expansion, the maximum sampling schedule is days 1, 2, 3, 5, and 6 of first cycle ]
  2. Disease response rate [ Time Frame: Scans will occur at screening and approximately every 2 months once the patient is on study medication for up to 1 year on study medication ]


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.


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

Inclusion Criteria:

  • Male or female patients 18 years of age or older
  • ECOG PS 0 or 1
  • Patients must have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3 chemotherapy regimens in this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable
  • Recovered from the effects of prior antineoplastic therapy
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
  • Male patients who agree to practice effective barrier contraception or agree to practice true abstinence
  • Voluntary written consent must be given before performance of any study-related procedure
  • Suitable venous access for the study-required blood sampling
  • Adequate clinical laboratory values during the screening period as specified in the protocol
  • Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924
  • Availability of fixed tumor specimen (block or slides) for exploratory biomarker analysis. If no slides or block are available, fresh tumor biopsies should be obtained and used for these assessments

Exclusion Criteria:

  • Major surgery within 14 days before the first dose of study drug
  • Female patients who are lactating or pregnant
  • Active uncontrolled infection or severe infectious disease
  • Receiving antibiotic therapy within 14 days before the first dose of study treatment
  • Life-threatening illness unrelated to cancer
  • Known hypersensitivity to study-assigned chemotherapy
  • Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel,carboplatin, and gemcitabine is allowed
  • History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for patients to be enrolled in Arm 1 (MLN4924 + docetaxel), history of hypersensitivity to carboplatin for patients to be enrolled in Arm 2 (MLN4924 + paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel (cremophor-based formulations) for patients to be enrolled in Arm 2
  • Persistent diarrhea (greater than Grade 2) lasting > 3 days within 2 weeks before the first dose of study treatment
  • Systemic antineoplastic therapy within 21 days before the first dose of study drug
  • Radiotherapy within 14 days preceding the first dose of study treatment
  • Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow
  • Treatment with CYP3A inducers within 14 days before the first dose of MLN4924. Treatment with CYP3A inhibitors within 14 days before the first dose of MLN4924; however, voriconazole and fluconazole need only be stopped for 3 days before MLN4924. Patients must have no history of amiodarone use in the 6 months before the first dose of MLN4924
  • Clinically uncontrolled central nervous system (CNS) involvement
  • Any serious medical or psychiatric illness
  • Treatment with any investigational products 21 days prior to treatment
  • Patients currently taking statins who are unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration
  • Known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • Known hepatic cirrhosis
  • Known cardiac/cardiopulmonary disease
  • Left ventricular ejection fraction
  • Patients with a cardiac pacer whose heart rate is set at a fixed rate and patients on concomitant medication that may limit increase in heart rate in response to hypotension
  • History of severe intolerance to cytotoxic agent(s) given in the assigned arm

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): NCT01862328


Locations
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United States, Georgia
Atlanta, Georgia, United States, 30322
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland, Ohio, United States, 44106-4948
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01862328    
Other Study ID Numbers: C15010
First Posted: May 24, 2013    Key Record Dates
Last Update Posted: June 11, 2018
Last Verified: June 2018
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
MLN4924
Solid Tumors
Additional relevant MeSH terms:
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Neoplasms
Gemcitabine
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Carboplatin
Pevonedistat
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs