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

4 november 2019 bijgewerkt door: Millennium Pharmaceuticals, Inc.

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

8

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Hongarije
      • Budapest, Hongarije, 1062
        • Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly
      • Budapest, Hongarije, 1076
        • PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. 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.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  3. Expected survival longer than 3 months from enrollment in the study.
  4. Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the effects of prior antineoplastic therapy.

Exclusion Criteria:

  1. 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.
  2. Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Ander
  • Interventioneel model: Sequentiële toewijzing
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: [14C]-Pevonedistat 25 mg/m^2
[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.
Geneesmiddel: Pevonedistat
Pevonedistat intraveneuze infusie.
Andere namen:
  • MLN4924; TAK-924
Geneesmiddel: Docetaxel
Docetaxel intraveneuze infusie.
Geneesmiddel: Carboplatine
Carboplatine intraveneuze infusie.
Geneesmiddel: Paclitaxel
Paclitaxel intraveneuze infusie.
Geneesmiddel: [14C]-Pevonedistat
[14C]-Pevonedistat intravenous infusion.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
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
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
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
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Part A: Renal Clearance (CLR) for Pevonedistat
Tijdsspanne: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Tijdsspanne: 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)
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)
Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces
Tijdsspanne: Up to 168 hours post-dose
Up to 168 hours post-dose
Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
Tijdsspanne: Up to Cycle 11 (Cycle length =21 days)
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).
Up to Cycle 11 (Cycle length =21 days)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Millennium Pharmaceuticals, Inc.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

11 mei 2017

Primaire voltooiing (Werkelijk)

8 februari 2018

Studie voltooiing (Werkelijk)

5 november 2018

Studieregistratiedata

Eerst ingediend

14 februari 2017

Eerst ingediend dat voldeed aan de QC-criteria

15 februari 2017

Eerst geplaatst (Werkelijk)

20 februari 2017

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 november 2019

Laatste update ingediend die voldeed aan QC-criteria

4 november 2019

Laatst geverifieerd

1 november 2019

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • Pevonedistat-1013
  • U1111-1169-6648 (Register-ID: WHO)
  • 2016-004132-37 (EudraCT-nummer)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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