AzTrials
AzTrials

Non-Small Cell Lung Cancer (NSCLC)Phase 2NCT04576208

A Study to Evaluate the Impact of Management Strategies on Gastrointestinal-Related Adverse Events in Participants With Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations Receiving TAK-788

A Phase 2 study testing TAK-788 and Antidiarrheal prophylaxis in people with Non-Small Cell Lung Cancer (NSCLC), run by Takeda.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

The purpose of the study is to characterize the incidence and severity of TAK-788-associated diarrhea in previously treated participants with locally advanced or metastatic non-small-cell lung cancer (NSCLC) whose tumors harbor EGFR exon 20 insertion mutations treated with TAK-788 when administered with or without… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer (NSCLC)
What is being tested?
TAK-788 and Antidiarrheal prophylaxis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Nov 2020to 31 Jul 2022
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Diagnosed with histologically or cytologically confirmed nonsquamous cell locally advanced (not suitable for definitive therapy) or metastatic non-small-cell lung cancer (NSCLC) (Stage IIIB or IV) NSCLC; and, has received at least 1 prior line of therapy for this disease.
  • A documented epidermal growth factor receptor (EGFR) mutation with in-frame exon 20 insertion, confirmed as follows:
  • For sites located in the United States (US): assessment must be done by a certified laboratory functioning under the guidelines of the Clinical Laboratory Improvements Amendment (CLIA).
  • For site located outside of the US: assessment must be done by an accredited local laboratory.
  • Note: A documented EGFR in-frame exon 20 insertion or insertion-duplication includes but is not limited to one of the following:
  • A763_Y764insFQEA,
Show all 15Show fewer
  • V769_D770insASV (also referred to as ASV duplication)
  • D770_N771insNPG
  • D770_N771insSVD (also referred to as SVD duplication)
  • H773_V774insNPH (also referred to as NPH duplication), or
  • Any other in-frame insertion mutation in the exon 20 [amino acids 739 -823].
  • The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations. The reported insertion-duplication can have been detected on either tissue or liquid biopsy using a well-validated test based on either polymerase chain reaction, sequencing or next-generation sequencing (NGS).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Minimum life expectancy of ≥3 months.
  • All toxicities from prior therapy have been resolved to ≤Grade 1, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 or have resolved to baseline, at the time of first dose of TAK-788.

Who cannot join

  • Has been diagnosed with another primary malignancy other than NSCLC, except for the following:
  • Adequately treated non-melanoma skin cancer or cervical cancer in situ.
  • Definitively treated non-metastatic prostate cancer.
  • Non-NSCLC primary malignancies that are definitively relapse-free for ≥3 years.
  • Has unstable brain metastases to include previously untreated intracranial central nervous system (CNS) metastases or previously treated intracranial CNS metastases with radiologically documented new or progressing CNS lesions.
  • Brain metastases that are stable do not preclude eligibility if they have been treated with surgery and/or radiation, and have been stable without requiring corticosteroids to control symptoms within 7 days before randomization, and have no evidence of new or enlarging brain metastases.
Show all 13Show fewer
  • Has a current spinal cord compression (symptomatic or asymptomatic that is detectable by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
  • Currently has or has had a history of interstitial lung disease, to include radiation or drug related pneumonitis that requires/required steroid treatment.
  • Has an ongoing or active infection, to include but not limited to infections requiring intravenous antibiotics or has a known history of HIV. Testing for HIV is not required in the absence of history.
  • Note: Hepatitis B surface antigen-positive participants are allowed to enroll if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is below 1000 copies/mL in the plasma. Patients who are positive for anti-hepatitis C virus antibody can be enrolled but must not have detectable hepatitis C virus (HCV) RNA in the plasma.
  • Have uncontrolled hypertension. Participants with hypertension should be under treatment on study entry to control blood pressure.
  • A prolonged QTcF interval, or is being treated with medications known to be associated with the development of Torsades de Pointes.
  • Has a GI illness or disorder, including but not limited to a history of GI perforation, that could affect oral absorption of TAK-788.

About this study

Official title: A Randomized Open-label Phase 2 Multicenter Study to Evaluate the Impact of Management Strategies on Gastrointestinal-Related Adverse Events in Patients With Non-Small Cell Lung Cancer Harboring EGFR Exon 20 Insertion Mutations Receiving TAK-788

The purpose of the study is to characterize the incidence and severity of TAK-788-associated diarrhea in previously treated participants with locally advanced or metastatic non-small-cell lung cancer (NSCLC) whose tumors harbor EGFR exon 20 insertion mutations treated with TAK-788 when administered with or without intensive loperamide prophylaxis.

Read the detailed description

The drug being tested in this study is called TAK-788. TAK-788 administered with or without antidiarrheal prophylaxis is being tested to evaluate the impact of management strategies on gastrointestinal-related adverse events in participants with non-small cell lung cancer harboring EGFR Exon 20 insertion mutations receiving TAK-788.

The study will enroll approximately 90 patients. Participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups-

  • Cohort 1
  • Cohort 2

All participants will be asked to take TAK-788 capsules with or without a low-fat meal in Cohort 1 and TAK-788 capsule with antidiarrheal prophylaxis and with or without a low-fat meal in Cohort 2.

This is a multi-center trial and will be conducted worldwide. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic after receiving their last dose of drug for a follow-up assessment.

Being tested
TAK-788, Antidiarrheal prophylaxis
Keywords
Drug Therapy
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • TAK-788Drug

    Also called AP32788, Mobocertinib

    TAK-788 capsules

  • Antidiarrheal prophylaxisDrug

    Antidiarrheal prophylaxis includes loperamide tablet administered as per routine clinical practice.

Study groups in NCT04576208
Study groupRoleWhat they receive
Cohort 1ExperimentalTAK-788 160 mg, capsules, orally, once daily (QD) with or without a low-fat meal until disease progression or as assessed by the investigator during every 3-week cycle.
Receives: Drug: TAK-788
Cohort 2ExperimentalTAK-788 160 mg, capsules, orally, QD with or without a low-fat meal and antidiarrheal prophylaxis administered during the first 8 weeks of treatment until disease progression or as assessed by the investigator during every 3-week cycle.
Receives: Drug: TAK-788; Drug: Antidiarrheal prophylaxis

What is being measured

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

  1. Number of Participants with Treatment Emergent Adverse Events (TEAEs) of ≥Grade 3 Diarrhea Occurring During the First 4 Cycles of TAK-788 Dosing

    An Adverse Event (AE) is 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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Grading will be done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria. 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: Approximately 15 Months

Secondary outcomes (8)

  1. Number of Participants with TEAEs of ≥Grade 3 Nausea and Vomiting Occurring During the First 4 Cycles of TAK-788 Dosing

    An AE is 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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Grading will be done using the NCI-CTCAE criteria. 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: Approximately 15 Months

  2. Number of Participants With TEAEs of Diarrhea, Nausea, Vomiting and Other Adverse Event of Clinical Interest (AECIs) Occurring During the First 4 Cycles of TAK-788 Dosing

    An AE is 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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

    Measured: Approximately 15 Months

  3. Overall Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    ORR will be defined as the percentage of participants achieving complete response (CR) or partial response (PR). CR is defined as disappearance of all extranodal target lesions. PR is defined as at least a 30% decrease in Sum of the Longest Diameters (SLD) of target lesions, taking as a reference the baseline SLD.

    Measured: Approximately 15 Months

  4. Duration of Response as per RECIST Version 1.1

    DOR will be defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that PD is objectively documented. CR is defined as disappearance of all extranodal target lesions. PR is defined at least a 30% decrease in Sum of the Longest Diameters (SLD) of target lesions, taking as a reference the baseline SLD. PD is defined as at least a 20% increase in the Sum of Diameters (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: Approximately 15 Months

  5. Progression Free Survival (PFS) as per RECIST Version 1.1

    PFS will be defined as the interval from the randomization date until the first date at which the criteria for disease progression according to RECIST version 1.1 are met or death. PD is 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: Approximately 15 Months

  6. Health-Related Quality of Life (HRQoL) as Assessed European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 Score

    The EORTC QLQ-C30 is a cancer-specific questionnaire tested in participants with lung cancer. The EORTC QLQ-C30 will be scored for 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and a global health status/quality-of-life (QoL) scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QoL scale, higher scores represent better HRQoL, whereas for the symptom scales lower scores represent better HRQoL.

    Measured: Approximately 15 Months

  7. Health-Related Quality of Life (HRQoL) as Assessed by EORTC Lung Cancer Module (QLQ-LC13) Score

    The EORTC QLQ-LC13 module will comprise 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. The LC13 module incorporates 1 multi-item scale to assess dyspnea, and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis. Raw scores are converted into scale scores ranging from 0 to 100, where the higher scores represent worse symptoms and lower scores represent better HRQoL.

    Measured: Approximately 15 Months

  8. Health-Related Quality of Life (HRQoL) as Assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Score

    The NSCLC-SAQ is qualified by the US Food and Drug Administration (FDA) to measure symptoms of NSCLC. The NSCLC-SAQ has 7 items with 5-level verbal rating scale and measures the severity/frequency of the following NSCLC symptoms: cough, pain, dyspnea, fatigue, and appetite. The raw scores are ranged from 0 to 4 and total score is ranged from 0-20.

    Measured: Approximately 15 Months

Timeline

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

  1. First posted6 Oct 2020
  2. Study start30 Nov 2020 (estimated)
  3. Primary completion31 Jul 2022 (estimated)
  4. Study completion31 Jul 2022 (estimated)

Why it stopped: Business Decision (no safety or efficacy concerns)

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 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04576208
Sponsor's protocol ID
TAK-788-2001
Other IDs
2020-002045-41, U1111-1251-7658
Status last verified
Dec 2020
First submitted
30 Sep 2020
Last updated
17 Dec 2020
Results posted
No
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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TAK-788 and Antidiarrheal prophylaxis in people with Non-Small Cell Lung Cancer (NSCLC), run by Takeda.

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 15 inclusion and 13 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: withdrawn, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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 with Treatment Emergent Adverse Events (TEAEs) of ≥Grade 3 Diarrhea Occurring During the First 4 Cycles of TAK-788 Dosing (time frame: Approximately 15 Months). 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 NCT04576208.

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 17 Dec 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in