advanced, previously treated metastatic adenocarcinoma of the colon or rectum MedDRA version: 8.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer
Conditions
Interventions
Product Name: PTK787/ZK 222584
Product Code: SH T00268C
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Vatalanib succinate
CAS Number: 212142-18-2
Current Sponsor code: ZK 222584
Other d
Sponsors
Schering AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent obtained in accordance to local and institutional guidelines 2. Male or female patients aged = 18 years 3. Histologically confirmed metastatic adenocarcinoma of the colon or rectum 4. At least one line of prior standard chemotherapy for metastatic disease; standard systemic therapy for metastatic disease includes fluoropyrimidines, oxaliplatin and irinotecan 5. Measurable lesion(s) as per the modRECIST criteria (see Attachment 1) 6. At least 1 measurable liver lesion with the size of at least 3 cm for DCE-MRI evaluation (see Attachment 2) 7. WHO Performance status 0 to 2 8. Laboratory values obtained within the last 2 weeks before randomization: • Absolute neutrophil count (ANC) = 1.5 x 109/L • Platelets = 100 x 109/L • Hemoglobin = 9 g/dL • Serum creatinine = 1.5 times ULN • Serum bilirubin = 1.5 times ULN • Aspartate aminotransaminase (AST/SGOT) and alanine aminotransaminase (ALT/SGPT) = 3.0 times ULN (= 5times ULN, if liver metastases) • Urine negative for proteinuria based on dip stick reading or, if dip stick result is = '+1', then 24 hour urine collection with total urinary protein value = 500 mg and measured creatinine clearance = 50 mL/min 9. Life expectancy = 12 weeks 10. Negative pregnancy test not longer than 48 hours before administration of the study treatment for females of childbearing potential Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Full-field radiotherapy = 4 weeks or limited field radiotherapy = 2 weeks prior to randomization; patients must have recovered from all therapy-related toxicities 2. Chemotherapy = 3 weeks prior to randomization; patients must have recovered from all therapy-related toxicities (grade 1 neuropathy after oxaliplatin containing chemotherapy is allowed) 3. Biologic or immunotherapy = 6 weeks prior to randomization; patients must have recovered from all therapy-related toxicities 4. Concurrent use of other investigational agents and patients who have received investigational agents = 6 weeks prior to randomization 5. Concomitant use of proton pump inhibitors and H2-antagonists (please refer also to section 6.1). The use of antacids taken at least 2 hours before or after the study drug is allowed. 6. Major surgery = 4 weeks prior to randomization; minor surgery = 2 weeks prior to randomization. Insertion of a vascular access device is not considered as major or a minor surgery. Patients must have recovered from all surgery-related toxicities. 7. Pleural effusion or ascites that causes = CTC grade 2 dyspnoea 8. History or clinical signs of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis) 9. Concurrent severe and / or uncontrolled medical disease (i.e., uncontrolled diabetes, congestive cardiac failure, myocardial infarction within 6 months, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, chronic liver disease, confirmed diagnosis of human immunodeficiency virus (HIV) infection or active uncontrolled infection) or significant neurologic or psychiatric disorder, which could compromise participation in the study 10. History of another primary malignancy = 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin or cervical cancer in situ 11. Long QT syndrome or baseline 12-lead electrocardiogram (ECG) QTcF greater than 450 msec for males and 470 msec for females 12. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK/ZK (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, inability to swallow the tablets) 13. Pregnant or breastfeeding females 14. Subjects of both sexes unwilling or unable to use a required barrier method of contraception during participation1 15. Unwillingness or inability to comply with the study protocol 16. Previous assignment to treatment during this study 17. Presence of any condition excluding tumor scans by (DCE-) MRI (Attachment 2) or CT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the pharmacodynamic activity of PTK787/ ZK 222584 by dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) at trough levels in once daily (o.d.) versus twice daily (b.i.d.) treatment arms. ;Secondary Objective: The secondary objectives are to assess the efficacy, safety, tolerability, pharmacokinetics, and biomarker activity of o.d. versus b.i.d. administration of PTK787/ ZK 222584 monotherapy. ;Primary end point(s): The primary efficacy variable is the number of patients with at least 40% reduction in Ktrans from baseline to Day 28. | — |
Countries
France, Germany, Italy, Spain
Outcome results
None listed