advanced solid tumors Cancer
Conditions
Interventions
Gemcitabine, carboplatin and sorafenib in a cycle of 3 weeks.
Gemcitabine infusion every 1st and 8th day
Carboplatin infusion every 1st day
Sorafenib intake twice daily continuous.
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients with progressive advanced solid tumor who are considered for palliative gemcitabine plus carboplatinb combination chemotherapy. Furthermore: • > 18 years. • Performance: WHO 0 - 2. • Life expectancy > 3 months. • Histological or cytological proof of malignancy. • Measurable disease according to RECIST criteria. • Minimal acceptable safety laboratory values. o ANC of >= 1.5 × 109/L o Platelet count of >= 100 × 109/L o Haemoglobin level of >= 10 g/dL (>= 6.2 mmol/L) (prior transfusion is permitted) o Hepatic function as defined by serum bilirubin = 50 ml/min (by Cockcroft-Gault formula). • Able to swallow and retain oral medication. • Written informed consent. • Willingness to use a medically approved method of contraception • Caution is recommended when administering sorafenib with inhibitors of the CYP3A4 family (eg, ketoconazole, itraconazole, erythromycin, clarithromycin, warfarine).
Exclusion criteria
Exclusion criteria: • Previous investigational cytotoxic or biological treatment for malignant disease within 30 days before the start of the study. • Any treatment with non-oncological investigational drugs within 30 days before the start of the study. • Radiotherapy within 2 weeks prior to study entry. • Major surgery within 4 weeks prior to study treatment. • Patients using medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of sorafenib. • Pregnancy or breast feeding (all women of childbearing potential must have a pregnancy test before inclusion in the study; post-menopausal women must have amenorrhoea for at least 12 months). All patients must use 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. • Concurrent or previous malignancy of a different tumour type within five years of starting the study except for adequately treated non-melanoma skin cancer or cervical intraepithelial neoplasia • Legal incapacity • Uncontrolled or poorly controlled hypertension (Systolic blood pressure >= 150 mmHg, diastolic blood pressure >= 90 mmHg). Initiation or adjustment of blood pressure medications is permitted prior to study treatment provided that 3 consecutive BP readings are less than 150/90 mmHg, each separated by at least 24 hours • History of malabsorption syndrome or other disease that could significantly affect absorption of drugs • Systemic steroids within 2 weeks prior to study treatment • Myocardial infarction or cerebrovascular accident (CVA) within 6 months prior to study treatment • Congestive heart failure requiring medication. • Symptomatic brain metastases. • Hepatic dysfunction • Uncontrolled infections. • Known human immunodeficiency virus (HIV) infection • Known chronic or acute viral hepatitis • Patients who have known hypersensitivity to the study medication
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic endpoints will consist of parameters such as AUC, Css, Cmax, tmax and t1/2 of i.v. carboplatin and Gemcitabine and oral Sorafenib in combination. Assessment (according to RECIST criteria) of antitumor activity will be obtained every 2 cycles (6 weeks) and will be recorded as complete response, partial response, stable disease or progressive disease | — |
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability endpoints will consist of the evaluation of adverse events (AE*s), serious adverse events (SAE*s) and all clinically significant changes in clinical laboratory values. A dose regimen resulting in no more than 1 out of 6 patients with DLT will be estimated and defined as the optimally tolerated regimen. | — |
Countries
Netherlands
Outcome results
None listed