E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic cutaneous melanoma |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Objective:
To determine the efficacy of PTK787 in patients with metastatic cutaneous melanoma in terms of:
• response rate
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E.2.2 | Secondary objectives of the trial |
• Time to progression • Survival at 6 months and 1 year • Overall survival • Safety and toxicity • Correlation of pharmacological and genetic markers to response • Correlation of tumour vascularity and permeability to response
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with histologically or cytologically confirmed unresectable, metastatic cutaneous melanoma.
Life expectancy > 12 weeks.
Performance status 0, 1 or 2 (ECOG performance scale : Appendix A).
Presence of 1 or more bidimensionally measurable lesions, either clinically or radiologically (by chest x-ray, CT or conventional MRI scan as appropriate), using RECIST criteria.
Age > 18 years.
Laboratory parameters: Hb > 10 g/dl, platelets > 100,000 mm3, WCC > 3.0 x109/L, ANC > 1.5x109/L Bili < 1.5 x ULN, Alk phos < 3 x ULN, transaminases < 3 x ULN, (or alk phos and transaminases < 5 if liver metastases are present) Cr < 1.5 x ULN
Measured creatinine clearance > 50 ml/min and total urinary protein < 500 mg/24 hour .
Written informed consent provided by the patient.
Prior adjuvant therapy is allowed.
One line of prior systemic therapy for advanced disease is allowed.
Prior radiotherapy is allowed. However, measurable target lesions must not have been irradiated.
Patients must not have a history of other malignant disease other than adequately treated non-melanomatous skin cancer or in situ carcinoma of the cervix.
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E.4 | Principal exclusion criteria |
Any previous chemotherapy, immunotherapy or investigational agent within the last 4 weeks.
Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial.
Any medical or psychiatric condition which would influence the ability to provide informed consent.
Patients with a history of renal (eg. glomerulonephritis) or renal vascular disease.
Acute or chronic active liver disease (e.g., hepatitis, cirrhosis).
Surgery within 2 weeks of entry on to the study.
Incomplete recovery from previous surgery or non-surgical treatment.
History or presence of central nervous system (CNS) disease i.e., primary brain tumor, malignant seizures, clinically symptomatic CNS metastases or carcinomatous meningitis.
Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen; Unstable angina pectoris; Symptomatic congestive heart failure; Myocardial infarction ≤ 6 months prior to randomization; Serious uncontrolled cardiac arrhythmia; Uncontrolled diabetes; Active or uncontrolled infection.
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhoea which might result in malabsorption, any known malabsorption syndrome, bowel obstruction, or inability to swallow the capsules/tablets).
Patients who are taking warfarin or other similar oral anticoagulants that are metabolised by the cytochrome p450 system; heparin is acceptable.
Pregnant or lactating women.
Patients of both genders with reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
Women of childbearing potential must have a negative serum pregnancy test within 48 hours of trial entry.
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of trial will be the last Follow up visit of the last subject participating in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |