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.
Condition: Advanced Solid Tumors; Lymphomas
MeSH terms: Lymphoma
Intervention: Lenvatinib
Intervention description: Study phase dosing: participants received an initial single dose of radiolabelled 14C-lenvatinib oral patient dosing solution containing 24 mg of lenvatinib as anhydrous free base and radioactivity of 3.7 millibecquerel (MBq) on Day 1.
Extension phase dosing: 24 mg of 14C-lenvatinib: 2 x 10mg, and 4 x 1mg or 1 x 4mg tablets once-daily, continuously in each 28-day cycle during extension phase.
Intervention MeSH terms: Lenvatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Solid Tumors; Lymphomas

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.
    

Eligibility criteria:

        INCLUSION CRITERIA

          1. 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.

          2. 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

          3. Aged greater than or equal to 18 years

          4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

          5. Could take oral study medication

          6. Gave written informed consent to participate in the study

          7. Willing and complied with the study protocol for the duration of the study.

        EXCLUSION CRITERIA

          1. 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.

          2. Participants with meningeal carcinomatosis

          3. Any of the following values for 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. Prothrombin time (PT) [or International Normalized Ratio (INR)] and Patial
                  thromboplastin time (PTT) > 1.5 x the upper limit of normal (ULN)

               5. serum bilirubin greater than 1.5 x ULN

               6. other liver parameters greater than 3 x ULN

               7. creatinine clearance less than 60 mL/min per the Cockcroft and Gault formula

          4. Uncontrolled infections

          5. 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)

          6. 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

          7. Any treatment with an investigational drug within the last 30 days

          8. 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.

          9. Proteinuria greater than 1+ on bedside testing

         10. History of gastrointestinal malabsorption

         11. Surgery within four weeks of start of study treatment

         12. 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.

         13. 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

         14. Previous lenvatinib therapy

         15. History of alcoholism, drug addiction, psychiatric or psychological condition, or
             social situation which, in the opinion of the investigator, would impair study
             compliance

         16. History of allergic reactions attributed to compounds of similar chemical or
             biological composition to lenvatinib

         17. Other significant disease or disorder that, in the Investigator's opinion, would
             exclude the participant from the study

         18. Legal incapacity