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Solid TumorsPhase 1NCT01862328

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

A Phase 1 study testing MLN4924, Paclitaxel and Gemcitabine in people with Solid Tumors, run by Millennium Pharmaceuticals, Inc. at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to establish the maximum tolerated dose (MTD) and assess the safety and tolerability of MLN4924 (pevonedistat) in combination with docetaxel, paclitaxel and carboplatin, and gemcitabine in participants with solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
MLN4924, Paclitaxel and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
6 sitesUnited States
Study dates
10 Jun 2013to 21 May 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 years of age or older
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • 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 (that is, <=Grade 1 toxicity) from the effects of prior antineoplastic therapy
  • Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
  • Male participants who agree to practice effective barrier contraception or agree to practice true abstinence
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  • 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
  • Participants who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male participants) 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

Who cannot join

  • Major surgery within 14 days before the first dose of study drug
  • Female participants 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
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  • 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 participants to be enrolled in Arm 1 (MLN4924 + docetaxel), history of hypersensitivity to carboplatin for participants to be enrolled in Arm 2 (MLN4924 + paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel (cremophor-based formulations) for participants 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 greater than or equal to (>=) 25% of the hematopoietically active bone marrow
  • Treatment with cytochrome P450 3A (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. Participants must have no history of amiodarone use in the 6 months before the first dose of MLN4924 14. Clinically uncontrolled central nervous system (CNS) involvement 15. Any serious medical or psychiatric illness 16. Treatment with any investigational products 21 days prior to treatment 17. Unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration 18. Known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection 19. Known hepatic cirrhosis 20. Known cardiac/cardiopulmonary disease 21. Left ventricular ejection fraction 23. with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension 24 History of severe intolerance to cytotoxic agent(s) given in the assigned arm

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Study site

    Atlanta, Georgia, 30322

  • Study site

    Chapel Hill, North Carolina, 27599

  • Study site

    Cleveland, Ohio, 44106-4948

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    St Louis, Missouri, 63110

Other trials in United States

About this study

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

The purpose of this study is to establish the maximum tolerated dose (MTD) and assess the safety and tolerability of MLN4924 (pevonedistat) in combination with docetaxel, paclitaxel and carboplatin, and gemcitabine in participants with solid tumors.

Conditions
Solid Tumors
Keywords
MLN4924, Solid Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MLN4924Drug

    Also called Pevonedistat

    MLN4924 (intravenously [IV]) in participants in a 21-day cycle:

    • MLN4924 on Days 1,3,5 of each cycle

  • PaclitaxelDrug

    Paclitaxel (IV) in a 21-day cycle:

    • Paclitaxel on Day 1 of each cycle

  • GemcitabineDrug

    Gemcitabine (IV) in participants in a 28-day cycle:

    -Gemcitabine on Days 1,8,15 of each cycle

  • DocetaxelDrug

    Docetaxel (IV) in participants in a 21-day cycle:

    • Docetaxel on Day 1 of each cycle

  • CarboplatinDrug

    Carboplatin (IV) in participants in a 21-day cycle:

    • Carboplatin on Day 1 of each cycle
Study groups in NCT01862328
Study groupRoleWhat they receive
MLN4924 and Docetaxel (Arm 1)ExperimentalNot described
Receives: Drug: MLN4924; Drug: Docetaxel
MLN4924 + Paclitaxel + Carboplatin (Arm 2)ExperimentalNot described
Receives: Drug: MLN4924; Drug: Paclitaxel; Drug: Carboplatin
MLN4924 + Gemcitabine (Arm 3)ExperimentalNot described
Receives: Drug: MLN4924; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: Baseline up to 30 days after the last dose of study drug (up to 5 years)

  2. Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

    Measured: Baseline up to 30 days after the last dose of study drug (up to 5 years)

  3. Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

    Measured: Baseline up to 30 days after the last dose of study drug (up to 5 years)

Secondary outcomes (4)

  1. Percentage of Participants With Objective Response

    Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeter [mm]); no new lesions. PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions.

    Measured: Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3])

  2. Duration of Response

    Duration of response: time from the date of first documented response per the investigator response assessment (CR or PR) to the date of PD or the date of last disease assessment if the participant discontinued the study before PD using RECIST 1.1 CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis <10 mm); no new lesions. PR: >=30% decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in sum of diameters of target lesions, taking as reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

    Measured: From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years)

  3. Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924

    Measured: Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3])

  4. MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924

    The number of participants analyzed includes only those participants who had data available for this measure.

    Measured: Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 May 2013 (estimated)
  2. Study start10 Jun 2013
  3. Primary completion21 May 2018
  4. Study completion21 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01862328
Sponsor's protocol ID
C15010
Other IDs
U1111-1220-1470
Status last verified
Jun 2020
First submitted
15 May 2013
Last updated
22 Jun 2020
Data monitoring committee
No
Individual data sharing
Yes: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Publications

  • Faessel HM, Mould DR, Zhou X, Faller DV, Sedarati F, Venkatakrishnan K. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies. Br J Clin Pharmacol. 2019 Nov;85(11):2568-2579. doi: 10.1111/bcp.14078. Epub 2019 Sep 4.

    PubMed 31355467

  • Lockhart AC, Bauer TM, Aggarwal C, Lee CB, Harvey RD, Cohen RB, Sedarati F, Nip TK, Faessel H, Dash AB, Dezube BJ, Faller DV, Dowlati A. Phase Ib study of pevonedistat, a NEDD8-activating enzyme inhibitor, in combination with docetaxel, carboplatin and paclitaxel, or gemcitabine, in patients with advanced solid tumors. Invest New Drugs. 2019 Feb;37(1):87-97. doi: 10.1007/s10637-018-0610-0. Epub 2018 May 21.

    PubMed 29781056

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MLN4924, Paclitaxel and Gemcitabine in people with Solid Tumors, run by Millennium Pharmaceuticals, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01862328, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2020.

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