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Advanced Solid TumorsPhase 1NCT01773421

An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors

A Phase 1 study testing E7820 in people with Advanced Solid Tumors, run by Eisai Inc. at 6 sites in 2 countries.

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

This study consists of two Parts. Part A (Food Effect Study) and Part B (Determination of Maximum Tolerated Dose [MTD] for twice daily [BID] Dosing).Part A will be initiated first, and Part B will be initiated after the PK results of Part A have been evaluated. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
E7820
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
6 sitesin 2 countries
Study dates
30 Jun 2011to 12 Nov 2017
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

  • Age 18 years or older.
  • Histological or cytological evidence of an unresectable or refractory solid tumor.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Subjects with known brain metastases will be eligible under the following conditions A. Have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of brain disease recurrence or B. Have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of brain disease progression and C. Are asymptomatic and D. Discontinued corticosteroid treatment at least 30 days prior to Cycle 1, Day 1
  • Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the upper limits of normal (ULN) and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 x ULN (in the case of liver metastases less than or equal to 5 x ULN) In case 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 subject 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 the total alkaline phosphatase.
  • Adequate renal function as evidenced by serum creatinine less than or equal to 2.0 mg/dL (177 micro-mol/L) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula
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  • Provide written informed consent.
  • Are willing and able to comply with all aspects of the protocol.
  • Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L, hemoglobin greater than or equal to 9 g/dL (5.5 mmol/L) and platelet count greater than or equal to 100 x 109/L.
  • Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [beta-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of beta-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 (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (i.e., 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 (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double-barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. 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.
  • Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period and for 30 days after study drug discontinuation). No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.

Who cannot join

  • Leptomeningeal metastases or brain metastases (except as for inclusion criteria #4).
  • Active hemoptysis (at least 2.5 mL [0.5 teaspoon] bright red blood) within 3 weeks prior to the first dose of study drug.
  • Hypersensitivity to sulfonamide derivatives.
  • Subjects who have had radiation to greater than or equal to 30% of their bone marrow.
  • Subjects who require therapeutic anti-coagulant therapy with warfarin or related vitamin K antagonists. Prophylactic doses of heparin or low molecular weight heparin or thrombin inhibitors may be used in place of warfarin.
  • Left ventricular ejection fraction less than 50% on echocardiography or MUGA scanning.
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  • Anticancer therapies that have not been completed at least 28 days (42 days in the case of mitomycin C or nitrosoureas) prior to treatment with E7820 (other than surgery or treatment with a protein kinase inhibitor which must have been completed no less than one week prior to treatment with E7820).
  • Incomplete recovery from previous radiotherapy, chemotherapy, or surgery other than residual cutaneous effects or stable less than Grade 2 gastrointestinal toxicity.
  • History of an ischemic cardiac event, myocardial infarction or unstable cardiac disease within 3 months before study entry.
  • A clinically significant electrocardiogram (ECG) abnormality, including a marked baseline prolongation of QTc interval greater than 480 msec.
  • Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct.
  • Concurrent treatment with CYP3A4 inhibitors such as verapamil, cyclosporin, quinidine, erythromycin, mibefradil, clarithramycin and azoles.
  • Concurrent treatment with drugs known to be extensively metabolized by CYP2C9 and/or CYP2C19.
  • Chronic treatment with known inducers of CYP3A4 within four weeks of receiving treatment with E7820 other than corticosteroids (Appendix 6).
  • Subjects who have a positive test result for human immunodeficiency virus (HIV), hepatitis A, hepatitis B or hepatitis C.
  • Psychotic disorder(s) or unstable recurrent affective disorder(s) evident by use of antipsychotics or prior suicide attempt(s) within approximately the last 2 years.
  • History of drug or alcohol dependency or abuse within approximately the last 2 years.
  • Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
  • Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
  • Use of illegal recreational drugs.
  • Any medical or other condition that, in the opinion of the investigator, would preclude the subject's participation in a study.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • University College London Hospital

    London

  • The Christie Hospital

    Manchester

  • Sir Bobby Robson Cancer Trials Research Centre

    Newcastle

Other trials in United Kingdom

Netherlands2 sites

  • Netherlands Cancer Institute

    Amsterdam

  • University Medical Centre Utrecht

    Utrecht

Other trials in Netherlands

About this study

Official title: An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820, to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors

This study consists of two Parts. Part A (Food Effect Study) and Part B (Determination of Maximum Tolerated Dose [MTD] for twice daily [BID] Dosing).Part A will be initiated first, and Part B will be initiated after the PK results of Part A have been evaluated.

Being tested
E7820

What participants receive

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

  • E7820Drug

    FOOD EFFECT STUDY:

    Each subject (a minimum of 12 subjects) will be assigned according to a randomization code to receive a single 50 mg dose of E7820 on Day 1, either after fasting for 10 hours, or immediately after consuming a high fat breakfast. Following a 7-day washout period, the subjects will crossover and a second 50 mg dose of E7820 will be administered on Day 8.

  • E7820Drug

    MTD DETERMINATION FOR BID DOSING SCHEDULE

    The initial dose of E7820 will be 50 mg BID. If allowed by the rules for dose escalation, the dose escalations will be to 60 mg BID, 80 mg BID, and 100 mg BID.

Study groups in NCT01773421
Study groupRoleWhat they receive
Part AExperimentalNot described
Receives: Drug: E7820
Part BExperimentalNot described
Receives: Drug: E7820

What is being measured

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

  1. Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820

    Measured: Day 1 or 8: 0.5-48 hours

  2. Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820

    Measured: Day 1 or 8: 0.5-48 hours

  3. Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820

    Measured: Day 1 or 8: 0.5-48 hours

  4. Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule

    MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(<) 0.5*10^9/liter(L) for greater than(>) 5 days; neutropenia <1*10^9/L with fever; thrombocytopenia <25*10^9/L accompanied by bleeding or thrombocytopenia <10*10^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of >14 days required to recover from E7820-related toxicities.

    Measured: Up to Cycle 6 (Cycle length =28 days)

Secondary outcomes (4)

  1. Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR)

    BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for >4 weeks or stable disease (SD) for >5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (<10 millimeter [mm] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

    Measured: From first dose of study drug (Baseline) up to approximately 6.6 years

  2. Extension Phase Part A, and Treatment and Extension Phase Part B: Duration of Response

    Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

    Measured: From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years)

  3. Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD)

    PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported.

    Measured: From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years)

  4. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms.

    Measured: From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)

Timeline

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

  1. First posted23 Jan 2013 (estimated)
  2. Study start30 Jun 2011
  3. Primary completion30 Apr 2014
  4. Study completion12 Nov 2017

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
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01773421
Sponsor's protocol ID
E7820-E044-110
Other IDs
2010-023655-28
Status last verified
Feb 2018
First submitted
17 Jan 2013
Last updated
22 Jun 2023
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing E7820 in people with Advanced Solid Tumors, run by Eisai Inc. at 6 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 13 inclusion and 21 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 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom, 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 18 Jan 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?

Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820 (time frame: Day 1 or 8: 0.5-48 hours). The study lists 4 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 NCT01773421.

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 22 Jun 2023.

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