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TumorsPhase 1NCT02540291

Study of E7046 in Subjects With Selected Advanced Malignancies

A Phase 1 study testing E7046 in people with Tumors, run by Eisai Inc. at 3 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open label, multicenter, Phase 1 study of E7046 to assess the safety and tolerability of E7046 and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of E7046. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Tumors
What is being tested?
E7046
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
3 sitesin 2 countries
Study dates
30 Jul 2015to 27 Feb 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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age greater than or equal to 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Life expectancy greater than or equal to 12 weeks
  • Participants must have any of the following tumor types, confirmed by available pathology records or current biopsy, that is advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists: pancreatic adenocarcinoma, renal clear cell carcinoma, SCCHN (squamous cell carcinoma of head and neck), NSCLC (non-small cell lung cancer), colorectal cancer (CRC), hepatocellular carcinoma (HCC), ovarian serous epithelial cancer, bladder transitional cancer, cervical cancer, and triple-negative breast cancer
  • Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events (AEs) have either returned to baseline or stabilized
  • Prior definitive radiation therapy must have been completed at least 6 weeks before study drug administration and the irradiated lesions should show evidence of progression if they are intended to be considered target lesions. Prior palliative radiotherapy must be completed at least 2 weeks before study drug administration. The radiotherapy-related side effects must have resolved before the study entry. No radiopharmaceuticals (strontium, samarium) will be allowed within 8 weeks before study drug administration.
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  • Participants must have accessible tumors and consent to repeated biopsy for performance of correlative tissue studies
  • Must have at least one measurable lesion per irRECIST (immune-related Response Evaluation Criteria Criteria in Solid Tumors):
  • At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST using computerized tomography/magnetic resonance imaging (CT/MRI)
  • Lesions that have had definitive external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation or brachytherapy must show evidence of progressive disease to be deemed a target lesion
  • Prior treated brain or meningeal metastases must be without evidence of progression (confirmed by MRI) for at least 8 weeks and off immunosuppressive doses of systemic steroids (greater than 10 mg/day prednisone or equivalent) for at least 4 weeks before study drug administration
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses greater than 7.5 to 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
  • Participants with prior Hepatitis B or C are eligible on the condition that participants have adequate liver function as defined by Inclusion Criterion number 16 and Exclusion Criterion number 5
  • Left ventricular ejection fraction (LVEF) greater than 50% on echocardiography or multiple gated acquisition (MUGA) scan
  • Adequate renal function defined as serum creatinine less than 1.5 X ULN (upper limit of normal) or use SI units or calculated creatinine clearance greater than or equal to 50 mL/min per the Cockcroft and Gault formula
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/ul)
  • Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)
  • Hemoglobin greater than or equal to 9.0 g/dL
  • Adequate liver function:
  • Total bilirubin less than or equal to 1.5 X ULN except for unconjugated hyperbilirubinemia of Gilbert's syndrome
  • Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to 5 X ULN if participant has liver metastases). If alkaline phosphatase is greater than 3 X ULN (in absence of liver metastases) or greater than 5 X ULN (in presence of liver metastases) AND the participant also is known to have bone metastases, the liver-specific alkaline phosphatase must be separated from the total and used to assess the liver function instead of total alkaline phosphatase
  • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5
  • Willing and able to comply with all aspects of the protocol
  • Provide written informed consent prior to any study-specific screening procedures
  • Females must not be lactating or pregnant at screening or baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-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. All females will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing). Females of childbearing potential must not have had unprotected sexual intercourse within 30 days prior to study entry and must agree to use a highly effective method of contraception, from the last menstrual period prior to initiation of treatment, during Treatment Cycles, and for 30 days after the final dose of study treatment, and have a male partner who uses a condom. Highly effective contraception includes:
  • Double barrier methods of contraception such as condom plus diaphragm or cervical/vault cap with spermicide
  • Placement of an intrauterine device
  • Established hormonal contraceptive methods: oral, injectable, or implant. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks prior to dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. Female participants exempt from this requirement are participants who practice total abstinence or have a male partner who is vasectomized with confirmed azoospermia. If currently abstinent, the participant must agree to use a double barrier method as described above if they become sexually active during the Treatment Cycles, and for 30 days after study drug discontinuation
  • Male participants must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (ie, not of childbearing potential or practicing highly effective contraception and use a condom throughout the study period and for 90 days after study drug discontinuation)

Who cannot join

  • Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast that has completed curative therapy
  • Participants with any active autoimmune disease (Appendix 2) or a documented history of autoimmune disease, poorly controlled asthma or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy. Participants with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
  • Participants with inflammatory bowel disease
  • Known human immunodeficiency virus (HIV) infection
  • Active infection requiring therapy, including known positive tests for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA
  • 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 or absorbable topical corticosteroids except inhaled or intranasal corticosteroids (with minimal systemic absorption)
  • Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of E7046
  • Any other major illness that, in the investigator's judgment, will substantially increase the risk associated with the participant's participation in this study
  • Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter) before study drug administration
  • Prior exposure to drugs that are antagonists of colony stimulating factor-1 receptor (CSF1R) like but not limited to emactuzumab (RG7155) (Roche), PLX3397 (Plexicon), and JNJ40346627 (J \& J)
  • Use of any live vaccines (eg, intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) within 28 days
  • Prolongation of corrected QT [QTcF (Fridericia's corrected QT interval)] interval to greater than 480 msec when electrolytes balance is normal
  • Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac arrhythmia requiring medical treatment (including oral anticoagulation)
  • Females who are pregnant (positive urine test) or breastfeeding
  • Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Study site

    Boston, Massachusetts

  • Study site

    Houston, Texas

Other trials in United States

France1 site

  • Study site

    Villejuif, Cedex

Other trials in France

About this study

Official title: An Open-Label Multicenter Phase 1 Study of E7046 in Subjects With Selected Advanced Malignancies

This is an open label, multicenter, Phase 1 study of E7046 to assess the safety and tolerability of E7046 and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of E7046.

Read the detailed description

The study will be conducted in 2 parts: a dose escalation part to determine the MTD and/or RP2D of E7046, and a cohort expansion part with 6 to 16 participants to better characterize safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) at the RP2D. In the dose escalation part, increasing doses of E7046 will be administered to cohorts of 6 participants, at dose levels ranging from 125 mg to 750 mg.

Conditions
Tumors
Being tested
E7046
Keywords
E7046, Advanced malignancies, malignancies
Medical subject headings
Neoplasms

What participants receive

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

  • E7046Drug

    E7046 will be administered as a single agent orally once daily (QD) continuously in 21-day cycles. In the dose escalation part, increasing doses of E7046 ranging from 125 mg to 750 mg will be administered to cohorts of 6 participants. In the cohort expansion part, participants will be treated at the RP2D.

Study groups in NCT02540291
Study groupRoleWhat they receive
E7046ExperimentalParticipants with tumor types that harbor high levels of myeloid infiltrate based on the Cancer Genome Atlas (TCGA).
Receives: Drug: E7046

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) and Serious Adverse Events (SAEs)

    Measured: From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 2 years)

  2. Maximum Tolerated Dose (MTD) of E7046

    Measured: Cycle 1 (21 days)

  3. Recommended Phase 2 Dose (RP2D) of E7046

    Two RP2Ds were planned to be evaluated.

    Measured: Cycle 1 (21 days)

Secondary outcomes (5)

  1. Objective Response Rate (ORR)

    The ORR is the percentage of participants achieving a best overall response of confirmed immune-related partial response (irPR) + immune-related complete response (irCR), according to immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1, from first dose date until disease progression/recurrence.

    Measured: From first dose date until disease progression/recurrence (approximately up to 2 years)

  2. Progression-free Survival (PFS)

    PFS is defined as the time from first dose date to the date of the first documentation of confirmed disease progression or death, whichever occurs first, according to irRECIST v1.1. PFS was calculated using Kaplan-Meier product-limit method and Greenwood Formula.

    Measured: From first dose date to the date of the first documentation of confirmed disease progression or death (approximately up to 2 years)

  3. Duration of Response (DOR)

    The DOR is defined as the time from the date of first documented confirmed irCR/irPR, according to irRECIST v1.1 until the first documentation of confirmed disease progression or death, whichever came first.

    Measured: From the date of first documented confirmed irCR/irPR until the first documentation of confirmed disease progression or death (approximately up to 2 years)

  4. Disease Control Rate (DCR)

    The DCR is percentage of participants achieving best overall response of confirmed irCR, irPR, or immune-related stable disease (irSD) (lasting at least 5 weeks), according to irRECIST v1.1 from the first dose date until disease progression/recurrence.

    Measured: From the first dose date until disease progression/recurrence (approximately up to 2 years)

  5. Clinical Benefit Rate (CBR)

    The CBR is the percentage of participants achieving irPR + irCR + irSD (lasting at least 24 weeks), according to irRECIST v1.1 from first dose date until disease progression/recurrence.

    Measured: From first dose date until disease progression/recurrence (approximately up to 2 years)

Timeline

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

  1. First posted3 Sep 2015 (estimated)
  2. Study start30 Jul 2015
  3. Primary completion27 Feb 2018
  4. Study completion27 Feb 2018

Why it stopped: Terminated due to, licensing agreement granting exclusive rights of research, development, manufacture and marketing of Eisai's E7046 to Adlai Nortye Biopharma.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02540291
Sponsor's protocol ID
E7046-G000-101
Other IDs
2014-004823-37, 2014
Status last verified
Jul 2018
First submitted
25 Aug 2015
Last updated
17 Feb 2020
Data monitoring committee
No

Publications

  • Hong DS, Parikh A, Shapiro GI, Varga A, Naing A, Meric-Bernstam F, Ataman O, Reyderman L, Binder TA, Ren M, Liu M, Dayal S, Siu AY, Sachdev P, Xu L, Bhagawati-Prasad V, Tchakov I, Ooi CE, Bao X, Marabelle A. First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers. J Immunother Cancer. 2020 Jun;8(1):e000222. doi: 10.1136/jitc-2019-000222.

    PubMed 32554609

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E7046 in people with Tumors, run by Eisai Inc. at 3 sites in 2 countries.

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 30 inclusion and 16 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: stopped early, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, France. 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 17 Feb 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?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 2 years)). 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 NCT02540291, 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 17 Feb 2020.

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