Phase 1
Completed N=6
A Study to Determine the Metabolism and Elimination of 14C-E7080 in Patients With Advanced Solid Tumors or Lymphomas, Who Are Unsuitable For, or Have Failed, Existing Therapies.
Source: ClinicalTrials.gov NCT02578316 ↗Enrolled (actual)
6
Serious AEs
50.0%
Results posted
Jun 2017
Primary outcomePrimary: Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib — 485.2; 426.8 ng/mL
Summary
The purpose of this study was to determine the metabolism and elimination of 14C-lenvatinib in participants with advanced solid tumors or lymphomas, who were unsuitable for, or had failed, existing therapies.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib |
485.2; 426.8 | — |
| PRIMARY Time of Maximum Plasma Concentration (Tmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib |
1.418; 1.604 | — |
| PRIMARY Terminal Phase Rate Constant (λz) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma |
0.039; 0.020 | — |
| PRIMARY Terminal Exponential Half-life (t1/2) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma |
17.78; 34.54 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC(0-t)) |
5223; 3440 | — |
| PRIMARY Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf)) |
5783; 3469 | — |
| PRIMARY Percentage of Area Under the Plasma Concentration Curve Extrapolated to Infinity (%AUC(Extra)) |
8.637; 0.786 | — |
| PRIMARY Apparent Clearance (CL/F) of Lenvatinib From Plasma |
6.739 | — |
| PRIMARY Apparent Terminal Volume of Distribution in the Terminal Phase of Lenvatinib (Vz/F) |
335.7 | — |
| PRIMARY Renal Clearance of Lenvatinib (CLr) |
0.042 | — |
| PRIMARY Percentage Recovery of 14^C- Lenvatinib Related Material in the Urine |
24.74 | — |
| PRIMARY Percentage Recovery of 14^C- Lenvatinib Related Material in the Feces |
63.56 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
100; 100; 50.0; 33.3; 83.3 | — |
| SECONDARY Objective Tumor Response |
0; 16.7; 50.0; 33.3 | — |
Eligibility Criteria
INCLUSION CRITERIA
- Participants with histologically and/or cytologically confirmed solid tumor or lymphoma who were resistant/ refractory to approved therapies or for whom no appropriate therapies were available. Participants with measurable tumors according to RECIST were desirable but not essential for inclusion.
- All previous treatment (including surgery and radiotherapy) must have been completed at least four weeks prior to study entry and any acute toxicity must have resolved
- Aged greater than or equal to 18 years
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Could take oral study medication
- Gave written informed consent to participate in the study
- Willing and complied with the study protocol for the duration of the study.
EXCLUSION CRITERIA
- Participants with brain or subdural metastases, unless they had completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs and/or symptoms of brain metastases those were stable for at least 4 weeks.
- Participants with meningeal carcinomatosis
- Any of the following values for 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;
- Prothrombin time (PT) [or International Normalized Ratio (INR)] and Patial thromboplastin time (PTT) > 1.5 x the upper limit of normal (ULN)
- serum bilirubin greater than 1.5 x ULN
- other liver parameters greater than 3 x ULN
- creatinine clearance less than 60 mL/min per the Cockcroft and Gault formula
- Uncontrolled infections
- Significant cardiovascular impairment (history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable ischemic heart disease including a myocardial infarction within six months of study start, or serious cardiac arrhythmia)
- Participants with marked baseline prolongation of QT/QT interval corrected for heart rate (QTc) interval (QTc interval greater than or equal to 500 msec) using the Fridericia method
- Any treatment with an investigational drug within the last 30 days
- Women who were pregnant or breast-feeding; women of childbearing potential with a positive pregnancy test at screening or no pregnancy test. Women of child-bearing potential unless (1) surgically sterile or (2) using adequate measures of contraception in the opinion of the Investigator (including two forms of contraception, one of which must be a barrier method). Perimenopausal women who were amenorrheic for at least 12 months to be considered of non-child-bearing potential. Fertile males with female partners of child-bearing potential who were not willing to use contraception, or whose female partners were not using adequate contraceptive protection, were excluded.
- Proteinuria greater than 1+ on bedside testing
- History of gastrointestinal malabsorption
- Surgery within four weeks of start of study treatment
- Bleeding or thrombotic disorders or use of an anticoagulant, such as warfarin, with a therapeutic INR. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), and low molecular weight heparin (LMWH) were permissible but when used with caution.
- Poorly controlled hypertension (defined as a change in hypertensive therapy within three months of study start) or participants diagnosed with hypertension (defined as a repeat blood pressure measurement of 160/90 mmHg or higher) at screening
- Previous lenvatinib therapy
- History of alcoholism, drug addiction, psychiatric or psychological condition, or social situation which, in the opinion of the investigator, would impair study compliance
- History of allergic reactions attributed to compounds of similar chemical or biological composition to lenvatinib
- Other significant disease or disorder that, in the Investigator's opinion, would exclude the participant from the study
- Legal incapaci
Data sourced from ClinicalTrials.gov (NCT02578316). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.