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Urinary Bladder NeoplasmsPhase 1NCT04109092

A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102

A Phase 1 study testing E7766 in people with Urinary Bladder Neoplasms, run by Eisai Inc. at 9 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intravesically in participants with NMIBC. Both intermediate risk and BCG-unresponsive NMIBC participants will be included. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urinary Bladder Neoplasms
What is being tested?
E7766
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
9 sitesUnited States
Study dates
13 Feb 2020to 29 Sep 2022
Phase
Phase 1
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

  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Life expectancy greater than (>) 2 years in the view of the investigator.
  • Participants must have biopsy proven transitional or predominantly transitional cell NMIBC.
  • For the Dose Escalation part of the study, the following participants will be included:
  • Both, lower and higher dose escalation cohorts:
  • Participants with intermediate risk NMIBC
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  • Only higher dose escalation cohorts:
  • Participants with BCG Unresponsive NMIBC despite prior adequate treatment. Furthermore, all participants should be indicated for radical cystectomy as the standard of care for BCG unresponsive NMIBC. Participants who are undergoing radical cystectomy as well as participants who have refused to undergo radical cystectomy will be eligible to participate in the Dose Escalation part of the study. For participants who are undergoing radical cystectomy, date of surgery should not be delayed more than 3 months after Day 1 of dosing.
  • For the Dose Expansion part of the study, the following participants will be included:
  • Participants with histologically confirmed
  • CIS (with or without concomitant non-muscle invasive, Ta or T1 papillary disease) (Arm 1) Or
  • Non-muscle invasive high-grade Ta or T1 papillary disease without CIS (Arm 2) that is deemed to be unresponsive to BCG therapy despite prior adequate treatment. Furthermore, participants should be indicated for radical cystectomy as the standard of care for BCG unresponsive NMIBC but have refused to undergo radical cystectomy.
  • Intermediate risk NMIBC: is defined as any participant with a high-grade Ta less than or equal to (<=) 3 cm or low-grade T1 tumor or with histologically confirmed multiple and/or recurrent low-grade Ta tumor with either 1 or 2 of the following 4 factors
  • Multiple tumors
  • Tumor >3 centimeter (cm)
  • Early recurrence (less than [<] year)
  • Frequent recurrences (>1 per year)
  • BCG Unresponsive NMIBC is defined as being at least 1 of the following:
  • Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
  • Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy.
  • T1 high-grade disease at the first evaluation following an induction BCG course
  • Adequate BCG therapy is defined as at least 1 of the following:
  • At least 5 of 6 doses of an initial induction course plus at least 2 of 3 doses of maintenance therapy.
  • At least 5 of 6 doses of an initial induction course plus at least 2 of 6 doses of a second induction course.
  • Participants must consent to repeat biopsies to allow the acquisition of fresh formalin-fixed paraffin embedded (FFPE) material (obtained within 8 weeks prior to treatment initiation with E7766)
  • Participants must consent to repeat blood draws as indicated in the schedule of assessments.
  • Participant must consent to providing cystectomy tumor sample in the event that cystectomy is performed following treatment with E7766.
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses >10 milligram per day (mg/d) prednisone or equivalent) must be safely discontinued at least 4 weeks before study drug administration.
  • Participants with prior Hepatitis B or C are eligible if they have adequate liver function.
  • Left ventricular ejection fraction (LVEF) >50 percent (%) on echocardiography or multiple gate acquisition (MUGA) scan.
  • Adequate renal function, bone marrow function and liver function.

Who cannot join

  • Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, or CIS of the cervix or breast that has completed curative therapy.
  • Participants with any active autoimmune disease or a documented history of autoimmune disease, except for participants with vitiligo or resolved childhood asthma/atopy
  • Presence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra or any other regional/metastatic disease.
  • Known human immunodeficiency virus (HIV) infection.
  • Active infection requiring therapy
  • Major surgery within 4 weeks before the first dose of study drug.
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  • Concurrent medical condition requiring the use of immunosuppressive medications or immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses >10 mg/d prednisone or equivalent).
  • Prolongation of corrected QT (corrected for QTc interval using Frederica's correction factors [QTcF]) interval to >480 millisecond (msec) when electrolytes balance is normal.
  • Significant cardiovascular impairment.
  • Use of illegal recreational drugs.
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 International Units Per Liter (IU/L) or equivalent units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
  • Currently enrolled in another clinical study or used any investigational drug or device within 28 days preceding Cycle 1 Day 1 (first dosing day).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43210

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • Indiana University

    Indianapolis, Indiana, 46202

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • University of Southern California

    Los Angeles, California, 90033

  • The Mount Sinai Hospital

    New York, New York, 10029

  • UCLA

    Santa Monica, California, 90404

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: INtravesical Phase 1/1b Study of STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intravesically in participants with NMIBC. Both intermediate risk and BCG-unresponsive NMIBC participants will be included.

Read the detailed description

The Phase 1/1b study consist of two parts: Dose Escalation and Dose Expansion. In the Dose Escalation Part, E7766 will be administered intravesically to participants with intermediate risk NMIBC or participants with BCG unresponsive NMIBC with increased dose levels to assess safety/tolerability profile of E7766 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of E7766. In the Dose Expansion Part, E7766 at RP2D will be administered to participants with NMIBC with or without carcinoma in situ (CIS) to confirm safety and assess preliminary clinical activity of E7766 as a single agent. Clinical activity will be evaluated by complete response (CR) rates at 3 months, 6 months, 12 months, 18 months, 24 months, and by duration of complete response (DOCR) in all participants who have achieved CR on treatment with E7766.

Being tested
E7766
Keywords
E7766, Non-Muscle Invasive Bladder Cancer, Intravesical administration, Ta or T1 Papillary Disease, Stimulator of Interferon Genes Agonist, Carcinoma in situ, BCG Unresponsive
Medical subject headings
Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms, Carcinoma in Situ

What participants receive

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

  • E7766Drug

    E7766, solution, intravesically.

Study groups in NCT04109092
Study groupRoleWhat they receive
Dose Escalation: NMIBC And BCG Unresponsive NMIBCExperimentalNot described
Receives: Drug: E7766
Dose Expansion: CIS With/Without Ta or T1ExperimentalNot described
Receives: Drug: E7766
Dose Expansion: High-grade Ta or T1, Without CISExperimentalNot described
Receives: Drug: E7766

What is being measured

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

  1. Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)

    DLTs are any of the toxicities occurring during the 6 weeks of the Induction Cycle and assessed by the investigator as related to study drug. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0).

    Measured: Baseline up to 6 weeks of the Induction Cycle (Cycle length is equal to [=] 6 weeks)

  2. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Baseline up to 30 days after the last dose of study drug (approximately 42 months)

  3. Dose Expansion Part: Complete Response Rate (CRR) at 3 Months

    Measured: Up to 3 months

  4. Dose Expansion Part: CRR at 6 Months

    Measured: Up to 6 months

  5. Dose Expansion Part: CRR at 12 Months

    Measured: Up to 12 months

  6. Dose Expansion Part: CRR at 18 Months

    Measured: Up to 18 months

  7. Dose Expansion Part: CRR at 24 Months

    Measured: Up to 24 months

Secondary outcomes (6)

  1. Dose Escalation Part: CRR at 3, 6, 12, 18 and 24 Months

    Measured: At Months 3, 6, 12, 18, and 24

  2. DOCR

    Measured: From the date of first documented CR until the first documentation of confirmed disease recurrence (approximately 42 months)

  3. Local Recurrence Free Rates

    Measured: At Months 6, 12, 18, and 24

  4. Cmax: Maximum Observed Plasma Concentration for E7766

    Measured: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)

  5. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766

    Measured: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)

  6. AUC: Area Under the Plasma Concentration Versus Time Curve for E7766

    Measured: Dose Escalation: Induction Phase: Day 1: 0-24 hour post dose; Day 15: 0-8 hour post dose; Maintenance Phase: Cycle 1: Day :0- 8 hours post dose; Dose Expansion: Induction Phase: Day 1, Day 15: 0-8 hour post dose (Cycle length is 3 weeks)

Timeline

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

  1. First posted30 Sep 2019
  2. Study start13 Feb 2020
  3. Primary completion29 Sep 2022 (estimated)
  4. Study completion29 Sep 2022 (estimated)

Why it stopped: There was no enrolment of participants.Unscheduled Clinical Study Closure - Eisai Network Company Decision, November 12, 2020.

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
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04109092
Sponsor's protocol ID
E7766-G000-102
Other IDs
2019-000161-21, 2019
Status last verified
Jul 2020
First submitted
27 Aug 2019
Last updated
14 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E7766 in people with Urinary Bladder Neoplasms, run by Eisai Inc. at 9 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 31 inclusion and 12 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 14 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 9 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?

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?

Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs) (time frame: Baseline up to 6 weeks of the Induction Cycle (Cycle length is equal to [=] 6 weeks)). The study lists 7 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 NCT04109092.

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 14 Dec 2020.

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