E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
non-resectable metastatic malignant 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 |
To evaluate the efficacy of PTK-ZK on metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy according to RECIST criteria. Further to evaluate the safety and tolerability of PTK-ZK in patients with metastatic melanoma either as a single agent treatment or in combination with standard chemotherapy |
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E.2.2 | Secondary objectives of the trial |
A side study shall evaluate anti-angiogenic and anti-lymphangiogenic effects of PTK-ZK and possible markers for treatment response in blood and tissue specimens |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1) Histologically confirmed nonresectable metastatic melanoma Stage III or IV (AJCC 2002) including patients with unknown primary melanoma, 2) Progressive disease, defined as an increase of tumour volume according to RECIST criteria, within the last 6 months, 3) Fulfilling the minimum RECIST requirements for evaluation of tumor response, 4) At least two cutaneous or soft tissue lesions that can be biopsized prior to and after treatment, respectively, 5) Able to undergo either contrast-enhanced CT scan or contrast-enhanced MRI scan for tumor assessment, 6) Life expectancy greater than 3 months, 7) ECOG performance status <2, 8) Age > 18 years, 9) Able to swallow and retain intact investigational drug tablets, 10) Willingness and ability to adhere to the study requirements as outlined in the protocol, 11) Agreement to use a highly effective method of birth control throughout the study period and 3 months thereafter for sexually active males and females of childbearing potential. 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. 12) Able to provide informed consent. |
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E.4 | Principal exclusion criteria |
1) One or more previous systemic therapies for metastatic melanoma, excluding prior systemic therapy given for high-risk primary tumor, lymph node metastasis, or other regional (AJCC stage III) disease spread as postoperative adjuvant therapy. 2) Anticancer therapy (chemotherapy, radiotherapy, vaccines, immunotherapy, and hormone therapy) delivered within 4 weeks prior to the 1st dose of study drug, and 2 weeks prior for palliative “spot” radiotherapy to bone metastases), 3) History of uveal melanoma, 4) Female patients who are pregnant or breast feeding. Women of childbearing potential must have a negative serum pregnancy test 48 hours prior to administration of study treatment. 5) Impaired organ and bone marrow function defined as one or more of the following: - Absolute neutrophil count (ANC) <1,500/ml, - Platelets <100,000/ml, - Total bilirubin >1.5 x ULN, - ASAT (SGOT)/ALAT (SGPT) > 3x ULN (5x if liver metastases are present) 6) History or presence of central nervous system (CNS) disease (i.e., primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis) 7) Another malignancy in the 5 years prior to enrollment other than non melanoma skin cancer, or cervix carcinoma in situ, 8) Major Surgery < 10 days prior to the start of study treatment 9) Inadequate recovery from previous surgery, radiation, chemo-, biologic or immunotherapy 10) Ongoing effects from previous investigational drug studies or concomitant participation in other investigational drug studies 11) Prior use of PTK-ZK or other VGEF receptor antagonists, 12) History of allergic reactions attributed to compounds of similar chemical or biologic composition to PTK-ZK, or patients who have known hypersensitivity to the study medication 13) 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, or inability to swallow the tablets). 14) Myocardial infarction ≤ 6 months prior to randomization 15) Acute or chronic liver disease (i.e., hepatitis, cirrhosis) 16) Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen 17) Chronic renal disease, i.e. - Creatinine >1.5* upper limit of normal (ULN) OR - Proteinuria based on dip stick reading positive > +1 OR - if the dip stick result is +1, total urinary protein > 500 mg and measured creatinine clearance < 50 ml/min from a 24-hour urine collection 18) Haemoglobin < 9 g/dL (patients may be transfused to achieve Hb > 9 g/dL) 19) Other uncontrolled concomitant condition, including but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, uncontrolled diabetes, seizure disorder 20) Psychiatric illness/social situations that would limit compliance with study requirements, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study 21) Human immunodeficiency virus (HIV) infection, 22) Prior enrollment into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall response defined by RECIST criteria |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | Information not present in EudraCT |
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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Study lasts until End-of-Treatment visit of the last patient |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |