A double-blind, randomized phase II study of once daily versus twice daily PTK787/ZK 222584 treatment in patients with advanced, previously treated metastatic adenocarcinoma of the colon or rectum - ND
- Conditions
- Advanced, previously treated Metastatic adenocarcinoma of the colon or rectumMedDRA version: 9.1Level: LLTClassification code 10061045Term: Colon neoplasm
- Registration Number
- EUCTR2006-004824-35-IT
- Lead Sponsor
- SCHERING
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 66
1. Signed written informed consent obtained in accordance to local and institutional
guidelines
2. Male or female patients aged 8805; 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) 8805; 1.5 x 109/L
? Platelets 8805; 100 x 109/L
? Hemoglobin 8805; 9 g/dL
? Serum creatinine 8804; 1.5 times ULN
? Serum bilirubin 8804; 1.5 times ULN
? Aspartate aminotransaminase (AST/SGOT) and alanine aminotransaminase
(ALT/SGPT) 8804; 3.0 times ULN ( 8804; 5times ULN, if liver metastases)
? Urine negative for proteinuria based on dip stick reading
or, if dip stick result is 8805; '+1', then 24-hour urine collection with total urinary protein
value 8804; 500 mg and measured creatinine clearance 8805; 50 mL/min
9. Life expectancy 8805; 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
1. Full-field radiotherapy 8804; 4 weeks or limited field radiotherapy 8804; 2 weeks prior to
randomization; patients must have recovered from all therapy-related toxicities
2. Chemotherapy 8804; 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 8804; 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 8804; 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 8804; 4 weeks prior to randomization; minor surgery 8804; 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 8805; 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 8804; 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is <br><br>to compare the pharmacodynamic activity of PTK787/ZK 222584 by DCE-MRI at trough levels in once daily and twice daily dosing treatment arms.;Secondary Objective: The secondary objectives are to assess once daily and twice daily PTK787/ZK 222584 dosing treatment arms for <br><br>?efficacy<br><br>?safety and tolerability<br><br>?pharmacokinetics<br><br>?biomarker activity;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.
- Secondary Outcome Measures
Name Time Method