Solid Tumor or LymphomaPhase 1NCT00121719
An Open Label Dose Escalation Study Of E7080
A Phase 1 study testing Lenvatinib in people with Solid Tumor or Lymphoma, run by Eisai Inc. at 2 sites in 2 countries.
Trial summary
The purpose of this study is to determine the maximum tolerated dose (MTD) of lenvatinib in patients with solid tumors or lymphomas. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor or Lymphoma
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Jul 2005to 1 Mar 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
- Patients must meet all of the inclusion criteria outlined below in order to be eligible to participate in the study:
- Patients with histologically and/or cytologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no appropriate therapies are available.
- All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have resolved.
- Aged greater than or equal to 18 years.
- Karnofsky performance status greater than or equal 70%.
- Written informed consent to participate in the study.
Who cannot join
- Patients with the following characteristics will not be eligible for the study:
- Brain tumors or brain or leptomeningeal metastases.
- Any of the following laboratory parameters:
- hemoglobin less than 9 g/dl (5.6 mmol/L)
- neutrophils less than 1.5 x 10^9/L
- platelets less than 100 x 10^9/L
Show all 23Show fewer
- serum bilirubin greater than 25 micro-mol/l (1.5 mg/dl)
- other liver parameters greater than 3 x the upper limit of normal (ULN)
- serum creatinine greater than 1.5 x ULN or creatinine clearance less than 60 ml/minute
- Uncontrolled infections.
- Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start.
- Any treatment with investigational drugs within 30 days before the start of the study.
- Pregnancy or lactation (all women of childbearing potential must have a negative pregnancy test before inclusion in the study; post-menopausal women must be amenorrheic for at least 12 months). Female patients of childbearing potential must use adequate contraceptive protection, defined as two forms of contraception, one of which must be a barrier method.
- Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection.
- History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance.
- Legal incapacity.
- Centrally located or squamous cell carcinoma of the lung.
- Proteinuria greater than 1+ on bedside testing.
- History of gastrointestinal malabsorption.
- Surgery involving gastro- and/or intestinal anastomosis within four weeks of study start.
- Patients with bleeding or thrombotic disorders.
- Patients using therapeutic dosages of anticoagulants.
- Poorly controlled hypertension (defined as a change in hypertensive therapy within three months of study start) or patients diagnosed with hypertension (defined as a repeat blood pressure measurement of 160/90 mmHg or higher) at screening.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
Netherlands Cancer Institute- Antoni Van Leeuwenhoek Hospital
Amsterdam, 1066 Cx
About this study
Official title: An Open Label Phase I Dose Escalation Study Of E7080
The purpose of this study is to determine the maximum tolerated dose (MTD) of lenvatinib in patients with solid tumors or lymphomas.
Read the detailed description
This is an open-label, non-randomized, dose escalation study. Patients will be treated with lenvatinib once daily. Each four-week treatment period will be considered to be one treatment cycle. The selection of subsequent dose levels will be performed according to an accelerated design: Although initially 3 patients per dose level will be entered, the next dose level can be opened for patient accrual after only the first patient in the previous cohort completes Cycle 1 with no drug-related toxicity greater than grade 1 (except alopecia, lymphopenia and anemia).
- Conditions
- Solid Tumor or Lymphoma
- Being tested
- Lenvatinib
- Keywords
- Resistant and refractory solid tumors, lymphomas, hodgkins disease, non-hodgkins lymphoma, neoplasms
- Medical subject headings
- Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080
Lenvatinib tablets taken orally, once daily.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose level at which no more than one out of six participants experienced dose-limiting toxicity (DLT). DLT was assessed during the first 4 weeks of therapy (Cycle 1) for dose escalation purposes. Participants enrolled into the MTD cohort were given the option to also participate in the food-effect pilot study. The food-effect pilot study was initiated once the MTD had been established.
Measured: Cycle 1 (4 weeks)
Secondary outcomes (16)
Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs)
All AEs were graded on a 5-point scale according to the National Cancer Institute's Common Toxicity Criteria (NCI CTC) grading system, version 3.0. Safety was assessed using the occurrence of DLTs, AEs, SAEs, clinical laboratory test results, vital signs measurements, physical examination findings, and electrocardiograms (ECGs) readings. An AE was defined as any untoward medical occurrence in a participant administered lenvatinib and did not necessarily have a causal relationship to lenvatinib. An SAE was defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect. Treatment-related AEs and SAEs are AEs considered probably or possibly related to lenvatinib.
Measured: First date of study treatment to date of last dose of study treatment, up to approximately 13 years and 8 months
Dose-limiting Toxicities (DLTs)
A DLT was defined as any grade 3 or higher hematological or non-hematological toxicity directly related to lenvatinib, any repeated National Cancer Institute Common Toxicity Criteria (NCI CTC) grade 2 hematological or non-hematological toxicity considered to be directly related to lenvatinib and required dose reduction, or failure to administer greater than or equal to 75% of the planned dosage of lenvatinib during Cycle 1 as a result of treatment-related failure.
Measured: Cycle 1 (4 weeks) of each dose level
Treatment-Related Adverse Events (All Grades) With an Overall Incidence Greater Than or Equal to 10%
Treatment-related AEs were untoward medical events that were considered by the investigator to be possibly or probably related to lenvatinib.
Measured: First date of study treatment to date of withdrawal from study or last dose of study treatment, up to approximately 13 years and 8 months
Best Overall Response (BOR)
BOR was the best confirmed response of complete response (CR), partial response (PR), progressive disease (PD), stable disease (SD), or not evaluable (NE), recorded from the start of lenvatinib until disease progression/recurrence or death. CR; disappearance of all target lesions for at least 1 month. PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD; a 20% or greater increase in the sum of the longest diameter of measured lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of one or more new lesions. SD; PR failed to be achieved in the overall response assessment and there was no PD observed at 7 weeks or later after starting lenvatinib.
Measured: Baseline to first date of documented CR, PR, SD, or PD, assessed up to approximately 4 years
Maximum Plasma Concentration (Cmax) of Lenvatinib
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Time to Maximum Plasma Concentration (Tmax) of Lenvatinib
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Apparent Plasma Half-life (t1/2) of Lenvatinib
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Area Under the Plasma Concentration Curve From Time 0 to Infinity (AUC(0-inf))
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC(0-24))
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Clearance Corrected for the Fraction of Lenvatinib Absorbed (CL/F)
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Apparent Volume of Distribution (Vz/F)
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Fraction of Unchanged Lenvatinib Excreted in the Urine (fe)
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Renal Clearance (CLr) of Lenvatinib
Measured: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on the Area Under the Curve From Zero to 24 Hours (AUC(0-24))
Measured: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on the Maximum Plasma Concentration (Cmax) of Lenvatinib
Measured: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on Time to Maximum Concentration (Tmax) of Lenvatinib
Measured: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2005 (estimated)
- Study start1 Jul 2005
- Primary completion19 Jun 2009
- Study completion1 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid Tumor or LymphomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00121719
- Sponsor's protocol ID
- E7080-E044-101
- Other IDs
- 2004-002265-21, 2004
- Status last verified
- Mar 2020
- First submitted
- 15 Jul 2005
- Last updated
- 22 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase I Dose Escalation Study Of E7080
- ClinicalTrials.gov ID
- NCT00121719
- Acronym / sponsor ID
- E7080-E044-101
- Conditions
- Solid Tumor or Lymphoma
- Keywords
- Resistant and refractory solid tumors, lymphomas, hodgkins disease, non-hodgkins lymphoma, neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jul 2005 (actual)
- Primary completion
- 19 Jun 2009 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 21 Jul 2005 (estimated)
- Results
- Posted 27 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the maximum tolerated dose (MTD) of lenvatinib in patients with solid tumors or lymphomas.
Detailed description
This is an open-label, non-randomized, dose escalation study. Patients will be treated with lenvatinib once daily. Each four-week treatment period will be considered to be one treatment cycle. The selection of subsequent dose levels will be performed according to an accelerated design: Although initially 3 patients per dose level will be entered, the next dose level can be opened for patient accrual after only the first patient in the previous cohort completes Cycle 1 with no drug-related toxicity greater than grade 1 (except alopecia, lymphopenia and anemia).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Lenvatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must meet all of the inclusion criteria outlined below in order to be eligible to participate in the study:
- Patients with histologically and/or cytologically confirmed solid tumor or lymphoma who are resistant/refractory to approved therapies or for whom no appropriate therapies are available.
- All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicities must have resolved.
- Aged greater than or equal to 18 years.
- Karnofsky performance status greater than or equal 70%.
Key exclusion criteria (23 listed)
- Brain tumors or brain or leptomeningeal metastases.
- Any of the following laboratory parameters:
- Uncontrolled infections.
- Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start.
- Any treatment with investigational drugs within 30 days before the start of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E7080Lenvatinib tablets taken orally, once daily. | Drug | 1 |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: Cycle 1 (4 weeks)
The MTD was defined as the highest dose level at which no more than one out of six participants experienced dose-limiting toxicity (DLT). DLT was assessed during the first 4 weeks of therapy (Cycle 1) for dose escalation purposes. Participants enrolled into the MTD cohort were given the option to also participate in the food-effect pilot study. The food-effect pilot study was initiated once the MTD had been established.
16 secondary outcomes
Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: First date of study treatment to date of last dose of study treatment, up to approximately 13 years and 8 months
Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (4 weeks) of each dose level
Treatment-Related Adverse Events (All Grades) With an Overall Incidence Greater Than or Equal to 10%
Time frame: First date of study treatment to date of withdrawal from study or last dose of study treatment, up to approximately 13 years and 8 months
Best Overall Response (BOR)
Time frame: Baseline to first date of documented CR, PR, SD, or PD, assessed up to approximately 4 years
Maximum Plasma Concentration (Cmax) of Lenvatinib
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Time to Maximum Plasma Concentration (Tmax) of Lenvatinib
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Apparent Plasma Half-life (t1/2) of Lenvatinib
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Area Under the Plasma Concentration Curve From Time 0 to Infinity (AUC(0-inf))
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC(0-24))
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Clearance Corrected for the Fraction of Lenvatinib Absorbed (CL/F)
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Apparent Volume of Distribution (Vz/F)
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Fraction of Unchanged Lenvatinib Excreted in the Urine (fe)
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Renal Clearance (CLr) of Lenvatinib
Time frame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on the Area Under the Curve From Zero to 24 Hours (AUC(0-24))
Time frame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on the Maximum Plasma Concentration (Cmax) of Lenvatinib
Time frame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Effect of Food on Time to Maximum Concentration (Tmax) of Lenvatinib
Time frame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenvatinib in people with Solid Tumor or Lymphoma, run by Eisai Inc. at 2 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 6 inclusion and 23 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 2 sites in Netherlands, United Kingdom. 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 27 May 2016). 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?
Maximum Tolerated Dose (MTD) (time frame: Cycle 1 (4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.