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Advanced Solid Tumors, Neoplasms, Advanced SolidPhase 1NCT03057366

A Study of [14 C]-Pevonedistat in Participants With Advanced Solid Tumors

A Phase 1 study testing Pevonedistat, [14C]-Pevonedistat and Docetaxel in people with Advanced Solid Tumors, Neoplasms, Advanced Solid, run by Millennium Pharmaceuticals, Inc. at 2 sites in Hungary.

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 assess the mass balance (that is, cumulative excretion of total radioactivity [TRA] in urine and feces) and to characterize the pharmacokinetics (PK) of pevonedistat in whole blood, plasma, and urine, and of TRA in plasma and whole blood following a single 1-hour infusion of 25… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pevonedistat, [14C]-Pevonedistat and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
2 sitesHungary
Study dates
11 May 2017to 5 Nov 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

  • Have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with one of the 2 chemotherapy regimens in Part B of this study (carboplatin+paclitaxel or docetaxel), or have progressed despite prior standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Expected survival longer than 3 months from enrollment in the study.
  • Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the effects of prior antineoplastic therapy.

Who cannot join

  • Has irregular defecation patterns (less than 1 defecation per 2 days or excessive diarrhea) and/or has a history of changes in bowel habits with daily routine or environment changes.
  • Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.

Trial locations and contacts

2 sites in 1 country.

Hungary2 sites

  • Magyar Honvédség Egészségügyi Központ Onkológiai osztály

    Budapest, 1062

  • PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely

    Budapest, 1076

Other trials in Hungary

About this study

Official title: A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors

The purpose of this study is to assess the mass balance (that is, cumulative excretion of total radioactivity [TRA] in urine and feces) and to characterize the pharmacokinetics (PK) of pevonedistat in whole blood, plasma, and urine, and of TRA in plasma and whole blood following a single 1-hour infusion of 25 milligram per square meter (mg/m^2) [14C]-pevonedistat intravenous (IV) solution containing approximately 60 to 85 microcurie (mCi) (approximately 2.22-3.145 megabecquerel [MBq]) of TRA in participants with advanced solid tumors in Part A.

Read the detailed description

The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people with advanced solid tumors.

The study will enroll approximately 4 to 6 pharmacokinetics (PK)-evaluable participants in part A. After completion of the mass balance and absorption, distribution, metabolism, excretion (ADME) assessment in Part A of the study, eligible participants will have the opportunity to continue into Part B at a secondary study site, which would begin in approximately 2 weeks of completion of Part A.

  • [14C]-Pevonedistat 25 mg/m^2
  • Part B (optional): Pevonedistat in combination with chemotherapy regimens (Pevonedistat 25 mg/m^2 + docetaxel 75 mg/m^2 or pevonedistat 20 mg/m^2 + carboplatin 20 mg/m^2 + paclitaxel 175 mg/m^2)

All participants will receive study drug via intravenous route. This multi-center trial will be conducted in Hungary. Participants will remain confined to the study site for 9 to 14 days in Part A. Participation in Part B is optional, participants will be re-evaluated for inclusion/exclusion criteria before administrating treatment. Participants will undergo treatment in Part B for a maximum of 12 cycles (21 days cycle each) and will include approximately 36 weeks for Part A and B combined. Participants will attend an end of study visit 30 days after the last dose of study drug in both Part A and B.

Being tested
Pevonedistat, [14C]-Pevonedistat, Docetaxel, Carboplatin, Paclitaxel
Keywords
Drug therapy
Medical subject headings
Neoplasms

What participants receive

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

  • PevonedistatDrug

    Also called MLN4924; TAK-924

    Pevonedistat intravenous infusion.

  • [14C]-PevonedistatDrug

    [14C]-Pevonedistat intravenous infusion.

  • DocetaxelDrug

    Docetaxel intravenous infusion.

  • CarboplatinDrug

    Carboplatin intravenous infusion.

  • PaclitaxelDrug

    Paclitaxel intravenous infusion.

Study groups in NCT03057366
Study groupRoleWhat they receive
[14C]-Pevonedistat 25 mg/m^2Experimental[14C]-pevonedistat (containing approximately 60-98 mCi [approximately 2.22-3.626 MBq] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. After completion of Part A, participants will have opportunity to continue into Part B. Participant will receive Pevonedistat 25 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles along with docetaxel 75 mg/m^2, infusion, intravenously, over 1 hour on Day 1 of each 21 day cycle; or pevonedistat 20 mg/m^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles, followed by paclitaxel 175 mg/m^2, infusion, intravenously, over 3 hours along with carboplatin 20 mg/m^2, infusion, intravenously, over 30 minutes on Day 1 of 21 each cycle up to 12 cycles. Based on investigator and sponsor discretion, participants deriving benefits will continue to receive current combination therapy or pevonedistat alone beyond 12 cycles.
Receives: Drug: Pevonedistat; Drug: [14C]-Pevonedistat; Drug: Docetaxel; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

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

  1. Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  2. Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  3. Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  4. Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  5. Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  6. Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  7. Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  8. Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  9. Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  10. Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  11. Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  12. Part A: Renal Clearance (CLR) for Pevonedistat

    Measured: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Secondary outcomes (3)

  1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Measured: Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days)

  2. Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces

    Measured: Up to 168 hours post-dose

  3. Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment

    The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

    Measured: Up to Cycle 11 (Cycle length =21 days)

Timeline

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

  1. First posted20 Feb 2017
  2. Study start11 May 2017
  3. Primary completion8 Feb 2018
  4. Study completion5 Nov 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
Intervention model
Sequential
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03057366
Sponsor's protocol ID
Pevonedistat-1013
Other IDs
U1111-1169-6648, 2016-004132-37, 2016
Status last verified
Nov 2019
First submitted
14 Feb 2017
Last updated
18 Nov 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
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

  • Zhou X, Sedarati F, Faller DV, Zhao D, Faessel HM, Chowdhury S, Bolleddula J, Li Y, Venkatakrishnan K, Papai Z. Phase I study assessing the mass balance, pharmacokinetics, and excretion of [14C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs. 2021 Apr;39(2):488-498. doi: 10.1007/s10637-020-01017-x. Epub 2020 Oct 22.

    PubMed 33089874

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pevonedistat, [14C]-Pevonedistat and Docetaxel in people with Advanced Solid Tumors, Neoplasms, Advanced Solid, run by Millennium Pharmaceuticals, Inc. at 2 sites in Hungary.

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 4 inclusion and 2 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 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Hungary. 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 8 May 2019). 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?

Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat (time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose). The study lists 12 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 NCT03057366, which also lists 1 linked publication.

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 18 Nov 2019.

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