Phase I Study of Indibulin in Patients With Solid Tumors

Dose-finding and Pharmacokinetic Trial of Orally Administered D-24851 to Patients With Solid Tumors

Dose-finding and pharmacokinetic trial of orally administered Indibulin to patients with solid tumors.

Inclusion Criteria

• Male or female patient, >= 18 years of age.
• Histologically/cytologically proven solid malignant tumor, for which standard treatment of proven efficacy are not or no longer available.
• Performance status 0-2 ECOG/WHO.
• Life expectancy > 3 months.
• Able and willing to undergo blood sampling for pharmacokinetics.
• Written informed consent.

Exclusion Criteria

• Safety concerns:
• Any non-compensated or uncontrolled non-malignant condition, such as, symptomatic heart failure, active tuberculosis or any other chronic or active infection.
• History of allergic reaction to one of the ingredients of the trial medication.
• Clinically relevant abnormality in organ function as evidenced by any of the following pa¬ra¬meters:
• White blood cell count: < 3.0 x 109/l ANC: < 1.5 x 109/l
• Thrombocytes: < 100 x 109/l
• Hemoglobin < 6.0 mM
• Bilirubin (total): > 1.5 times upper limit of normal range
• ASAT, ALAT: > 2.5 times upper limit of normal range unless related to metastases in which case > 5 times upper normal limit is allowed
• Creatinine (serum) > 135 µmol/l (> 1.5 mg/100ml) OR
• Creatinine clearance: < 50 ml/min (calculated according to modified Cockcroft and Gault)
• Breast feeding, pregnancy or planned pregnancy. A reliable method of contraception must be used in men and in women of childbearing potential during the study and for 3 months after last study drug administration.
• Lack of suitability for the trial:
• Concomitant treatment with any other investigational drugs or exposure to another investigational agent within the last 4 weeks prior to study specific screening procedures (period should be extended if the patient has received any drug which is known to have de¬layed toxicity or prolonged half-life).
• Active peptic ulcer or any GI condition that could alter absorption or motility.
• Chronic use of H2-antagonists or proton pump inhibitors.
• Any other cancer treatment during the study or administered within the last 4 weeks (6 weeks for nitrosoureas, mitomycin C, high-dose carboplatin or extensive radiotherapy) before start of study treatment, except irradiation of non-target lesions for symptom relief and bi-phosphonate treatment of bone metastases.
• Clinically symptomatic brain metastases or leptomeningeal disease.
• Neurological or psychiatric disease or drug or alcohol abuse which would interfere with the patients proper completion of the protocol assignment.
• Administrative reasons:
• Anticipated non-availability for study visits/procedures.