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Neoplasms, Advanced SolidPhase 1NCT03708211

A Study to Assess the Relative Bioavailability, Effect of Food, and Gastric Potential Hydrogen (pH) Modification on the Pharmacokinetics (PK) of TAK-931 in Participants With Advanced Solid Tumors

A Phase 1 study testing TAK-931 PIC, TAK-931 Tablet and Esomeprazole in people with Neoplasms, Advanced Solid, run by Millennium Pharmaceuticals, Inc. at 4 sites in Netherlands.

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 estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms, Advanced Solid
What is being tested?
TAK-931 PIC, TAK-931 Tablet and Esomeprazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
4 sitesNetherlands
Study dates
28 Mar 2019to 3 Dec 2019
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

  • Adult participants with histologically or cytologically confirmed metastatic or locally advanced or metastatic solid tumors for whom there is no available standard treatment with proven survival benefit, this therapy is not indicated, or it is refused by the participant. Based on the nonclinical data, the following indications may have a higher probability of clinical benefit: high-grade serous ovarian cancer, uterine carcinosarcoma, squamous esophageal cancer, squamous non-small cell lung carcinoma (NSCLC), rectal adenocarcinoma, and in general tumors with known tumor protein 53 (TP53) gene mutations. For any of these preferred indications, participants should have exhausted standard therapeutic options with a proven survival benefit.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy).
  • Suitable venous access for the study-required blood sampling including PK and pharmacodynamic sampling.
  • Must have a radiographically or clinically evaluable tumor, but measurable disease as defined by RECIST v1.1 is not required for participation in this study.

Who cannot join

  • Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.
  • Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, enzalutamide, mitotane, ritonavir, rifampin, or St John's wort within 14 days before the first dose of study drug.
  • With treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) during the screening period.
  • Part 2 only: known hypersensitivity to PPIs (example, angioedema or anaphylaxis have occurred).
  • Part 2 only: not being able or willing to take one high fat breakfast as indicated in the protocol.

Trial locations and contacts

4 sites in 1 country.

Netherlands4 sites

  • Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology

    Amsterdam, North Holland, 1066 CX

  • Leiden University Medical Center, Department of Clinical Oncology

    Leiden, South Holland, 2333 ZA

  • Radboud University Medical Center, Department of Medical Oncology

    Nijmegen, Gelderland, 6525 GA

  • Erasmus MC Cancer Institute, Department of Internal Oncology

    Rotterdam, South Holland, 3015 GD

Other trials in Netherlands

About this study

Official title: A Phase 1, Open-Label Study to Assess the Relative Bioavailability, Effect of Food, and Gastric pH Modification on the Pharmacokinetics of TAK-931 in Patients With Advanced Solid Tumors

The purpose of this study is to estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet.

Read the detailed description

The drug being tested in this study is called TAK-931. TAK 931 is being tested to treat participants who have advanced solid tumors. This study will look at relative bioavailability, effect of food and gastric pH modification on the PK of TAK-931.

The study will enroll approximately 44 participants. The study will be conducted in 2 parts: Part 1 and Part 2. In Part 1 and Part 2, participants will be randomly assigned (by chance, like flipping a coin) in a crossover design. In Part 1, participants will be assigned to 1 of the 2 following treatment sequences:

  • TAK-931 80 mg PIC + TAK-931 80 mg Tablet
  • TAK-931 80 mg Tablet + TAK-931 80 mg PIC

Part 2 of the study will be initiated, once the preliminary PK data from Part 1 is available to determine the relative bioavailability of the tablet formulation in reference to PIC and to calculate the single dose of TAK-931 tablet to be used in Part 2.In Part 2, participants will be assigned to 1 of the 2 following treatment sequences:

  • TAK-931 TBD Fed + TAK-931 TBD Fasted
  • TAK-931 TBD Fasted + TAK-931 TBD Fed

This multi-center trial will be conducted in the Netherlands. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic and will be contacted for approximately 30 days after receiving their last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first for a follow up assessment.

Being tested
TAK-931 PIC, TAK-931 Tablet, Esomeprazole
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.

  • TAK-931 PICDrug

    TAK-931 PICs.

  • TAK-931 TabletDrug

    TAK-931 Tablets.

  • EsomeprazoleDrug

    Esomeprazole Tablets.

Study groups in NCT03708211
Study groupRoleWhat they receive
Part1: TAK-931 80 mg PIC + TAK-931 80 mg TabletExperimentalTAK-931 80 milligram (mg), PIC, orally, once on Day 1 Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, tablet, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until progressive disease (PD), or unacceptable toxicity or any treatment discontinuation is determined.
Receives: Drug: TAK-931 PIC; Drug: TAK-931 Tablet
Part1: TAK-931 80 mg Tablet + TAK-931 80 mg PICExperimentalTAK-931 80 mg, tablet, orally, once on Day 1 of Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, PIC, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.
Receives: Drug: TAK-931 PIC; Drug: TAK-931 Tablet
Part 2: TAK-931 Fed + TAK-931 Fasted + Esomeprazole 40 mgExperimentalTAK-931 tablet, orally, once under fed state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fasted state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.
Receives: Drug: TAK-931 Tablet; Drug: Esomeprazole
Part 2: TAK-931 Fasted + TAK-931 Fed + Esomeprazole 40 mgExperimentalTAK-931 tablet, orally, once under fasted state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fed state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.
Receives: Drug: TAK-931 Tablet; Drug: Esomeprazole

What is being measured

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

  1. Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length is equal to [=] 16 days)

  2. Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)

  3. Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)

Secondary outcomes (10)

  1. Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)

  2. Part 1, CL/F: Oral Clearance for TAK-931

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)

  3. Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931

    Measured: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)

  4. Part 1: Overall Response Rate (ORR)

    ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD.

    Measured: Baseline up to 8 months

  5. Part 1: Progression-free Survival (PFS)

    PFS was defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occured first. Per RECIST V1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 millimeter (mm).

    Measured: From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurred first (up to 8 months)

  6. Part 1: Disease Control Rate (DCR)

    DCR was defined as the percentage of participants with CR, PR plus stable disease (SD) greater than or equal to (>=) 1 post baseline computed tomography (CT) scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

    Measured: Baseline up to 8 months

  7. Part 1: Duration of Response (DOR)

    DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm.

    Measured: From the date of first documentation of a response to the date of first documentation of PD ( up to 8 months)

  8. Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification

    Measured: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)

  9. Part 1: Percentage of Participants With Grade 3 or Higher TEAEs

    An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

    Measured: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)

  10. Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters

    Measured: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)

Timeline

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

  1. First posted17 Oct 2018
  2. Study start28 Mar 2019
  3. Primary completion3 Dec 2019
  4. Study completion3 Dec 2019

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03708211
Sponsor's protocol ID
TAK-931-1003
Other IDs
2017-004629-34, U1111-1214-4266, NL66709.091.18, 2017
Status last verified
Dec 2020
First submitted
12 Oct 2018
Last updated
29 Dec 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Steeghs N, Pruis M, van Herpen C, Lu V, Redman J, Zhou X. A phase 1 open-label study to assess the relative bioavailability of TAK-931 tablets in reference to powder-in-capsule in patients with advanced solid tumors. Invest New Drugs. 2023 Feb;41(1):53-59. doi: 10.1007/s10637-022-01318-3. Epub 2022 Nov 21.

    PubMed 36409435

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TAK-931 PIC, TAK-931 Tablet and Esomeprazole in people with Neoplasms, Advanced Solid, run by Millennium Pharmaceuticals, Inc. at 4 sites in Netherlands.

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 5 inclusion and 5 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 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Netherlands. 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 29 Dec 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?

Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC (time frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length is equal to [=] 16 days)). 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 NCT03708211, 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 29 Dec 2020.

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