Phase I study of gemcitabine and carboplatin plus sorafenib in patients with advanced solid tumors
- Conditions
- advanced solid tumorsCancer10027655
- Registration Number
- NL-OMON31053
- Lead Sponsor
- Antoni van Leeuwenhoek Ziekenhuis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 28
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 <= 1.25 times the upper limit of normal (ULN), ALT and AST <= 2.5 times the ULN, except if liver metastases then ALAT and ASAT < 5 times the ULN.
o Renal function as defined by serum creatinine <= 1.25 times ULN or creatinine clearance >= 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).
• 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety and tolerability endpoints will consist of the evaluation of adverse<br /><br>events (AE*s), serious adverse events (SAE*s) and all clinically significant<br /><br>changes in clinical laboratory values.<br /><br>A dose regimen resulting in no more than 1 out of 6 patients with DLT will be<br /><br>estimated and defined as the optimally tolerated regimen.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Pharmacokinetic endpoints will consist of parameters such as AUC, Css, Cmax,<br /><br>tmax and t1/2 of i.v. carboplatin and Gemcitabine and oral Sorafenib in<br /><br>combination.<br /><br>Assessment (according to RECIST criteria) of antitumor activity will be<br /><br>obtained every 2 cycles (6 weeks) and will be recorded as complete response,<br /><br>partial response, stable disease or progressive disease </p><br>