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 - Comparison of once daily versus twice daily administration of PTK787/ZK 222584 in mCRC

• Conditions: advanced, previously treated metastatic adenocarcinoma of the colon or rectum; MedDRA version: 8.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2006-004824-35-DE
• Lead Sponsor: Schering AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-22
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

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

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

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 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.<br>;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. <br>;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.