Clinical trial NCT00121719: An Open Label Dose Escalation Study Of E7080
Official title: An Open Label Phase I Dose Escalation Study Of E7080
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor or Lymphoma
Keywords: Resistant and refractory solid tumors
lymphomas
hodgkins disease
non-hodgkins lymphoma
neoplasms
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2005-07-21
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Eligibility criteria: INCLUSION CRITERIA:

Patients must meet all of the inclusion criteria outlined below in order to be eligible to participate in the study:

1. 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.
2. 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.
3. Aged greater than or equal to 18 years.
4. Karnofsky performance status greater than or equal 70%.
5. Written informed consent to participate in the study.

EXCLUSION CRITERIA:

Patients with the following characteristics will not be eligible for the study:

1. Brain tumors or brain or leptomeningeal metastases.
2. Any of the following laboratory parameters:

   1. hemoglobin less than 9 g/dl (5.6 mmol/L)
   2. neutrophils less than 1.5 x 10\^9/L
   3. platelets less than 100 x 10\^9/L
   4. serum bilirubin greater than 25 micro-mol/l (1.5 mg/dl)
   5. other liver parameters greater than 3 x the upper limit of normal (ULN)
   6. serum creatinine greater than 1.5 x ULN or creatinine clearance less than 60 ml/minute
3. Uncontrolled infections.
4. Clinically significant cardiac impairment or unstable ischemic heart disease including a myocardial infarction within six months of study start.
5. Any treatment with investigational drugs within 30 days before the start of the study.
6. 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.
7. Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection.
8. History of alcoholism, drug addiction, or any psychiatric or psychological condition which, in the opinion of the investigator, would impair study compliance.
9. Legal incapacity.
10. Centrally located or squamous cell carcinoma of the lung.
11. Proteinuria greater than 1+ on bedside testing.
12. History of gastrointestinal malabsorption.
13. Surgery involving gastro- and/or intestinal anastomosis within four weeks of study start.
14. Patients with bleeding or thrombotic disorders.
15. Patients using therapeutic dosages of anticoagulants.
16. 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1 (4 weeks)
Secondary outcomes:
measure: Summary of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: First date of study treatment to date of last dose of study treatment, up to approximately 13 years and 8 months
measure: Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 1 (4 weeks) of each dose level
measure: Treatment-Related Adverse Events (All Grades) With an Overall Incidence Greater Than or Equal to 10%
timeFrame: 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
measure: Best Overall Response (BOR)
timeFrame: Baseline to first date of documented CR, PR, SD, or PD, assessed up to approximately 4 years
measure: Maximum Plasma Concentration (Cmax) of Lenvatinib
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Time to Maximum Plasma Concentration (Tmax) of Lenvatinib
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Apparent Plasma Half-life (t1/2) of Lenvatinib
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Area Under the Plasma Concentration Curve From Time 0 to Infinity (AUC(0-inf))
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Area Under the Plasma Concentration Curve From Time 0 to 24 Hours (AUC(0-24))
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Clearance Corrected for the Fraction of Lenvatinib Absorbed (CL/F)
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Fraction of Unchanged Lenvatinib Excreted in the Urine (fe)
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Renal Clearance (CLr) of Lenvatinib
timeFrame: Cycles 1 and 2 Day 1: 0-24 hours postdose (Cycle length = 28 days)
measure: Effect of Food on the Area Under the Curve From Zero to 24 Hours (AUC(0-24))
timeFrame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
measure: Effect of Food on the Maximum Plasma Concentration (Cmax) of Lenvatinib
timeFrame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
measure: Effect of Food on Time to Maximum Concentration (Tmax) of Lenvatinib
timeFrame: Cycle 1 Day 15 and Day 22: 0-24 hours postdose (Cycle length = 28 days)
Other outcomes:
measure: Pharmacodynamic (PD) Biomarkers of Lenvatinib in Peripheral Blood Mononuclear Cells (PBMCs) and Tumor Samples
timeFrame: Blood: Cycle 1 Day 1, Day 15, or Day 22, Cycle 2 Day 1 Tumor tissue: Screening and after at least one 28-day Cycle of study treatment
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute- Antoni Van Leeuwenhoek Hospital
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
Study officials:
References: