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Phase II Randomized, Parallel-Group Trial on PTK-ZK With or Without DTIC in Patients With Non-resectable Metastatic Malignant Melanoma

Phase 1/Phase 2
18 Years
Not Enrolling

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Trial Information

Phase II Randomized, Parallel-Group Trial on PTK-ZK With or Without DTIC in Patients With Non-resectable Metastatic Malignant Melanoma

This is a multicenter, randomized, open-label, parallel-group phase II study to evaluate the
efficacy and safety of PTK-ZK in the treatment of patients with metastatic malignant
melanoma who do not qualify for surgical resection:

- progressive locoregionary disease not to be controlled by surgical measures

- distant metastasis other than brain metastasis not eligible for surgical resection or
radiotherapy All patients will be treated with PTK-ZK 1250mg administered orally once a
day for treatment cycles of 28 days. In case of unacceptable toxicity the dose can be
reduced to 1000 mg and further on to 750 mg daily.

Patients in Arm B additionally receive intravenous DTIC 850mg/m² on day 1 of each cycle.

After informed consent is given by the patient a biopsy from a metastasis should be taken
before the first intake of study medication and at the end of cycle 2 to specify markers of
angiogenesis and MVD (Micro vessel density).

Inclusion Criteria:

- Histologically confirmed nonresectable metastatic melanoma Stage III or IV (AJCC
2002) including patients with unknown primary melanoma,

- Progressive disease, defined as an increase of tumour volume according to RECIST
criteria, within the last 6 months,

- Fulfilling the minimum RECIST requirements for evaluation of tumor response,

- At least two cutaneous or soft tissue lesions that can be biopsised prior to and
after treatment, respectively,

- Able to undergo either contrast-enhanced CT scan or contrast-enhanced MRI scan for
tumor assessment,

- Life expectancy greater than 3 months,

- ECOG performance status <2,

- Age > 18 years,

- Able to swallow and retain intact investigational drug tablets,

- Willingness and ability to adhere to the study requirements as outlined in the

- 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.

- Able to provide informed consent.

Exclusion Criteria:

- 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.

- 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),

- History of uveal melanoma,

- 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

- Impaired organ and bone marrow function defined as one or more of the following:

- Absolute neutrophil count (ANC) <1,500/µl,

- Platelets <100,000/µl,

- Total bilirubin >1.5 x ULN,

- ASAT (SGOT)/ALAT (SGPT) > 3x ULN (5x if liver metastases are present)

- History or presence of central nervous system (CNS) disease (i.e., primary brain
tumor, malignant seizures, CNS metastases or carcinomatous meningitis)

- Another malignancy in the 5 years prior to enrollment other than non melanoma skin
cancer, or cervix carcinoma in situ,

- Major Surgery < 10 days prior to the start of study treatment

- Inadequate recovery from previous surgery, radiation, chemo-, biologic or

- Ongoing effects from previous investigational drug studies or concomitant
participation in other investigational drug studies

- Prior use of PTK-ZK or other VGEF receptor antagonists,

- 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

- 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).

- Myocardial infarction ≤ 6 months prior to randomization

- Acute or chronic liver disease (i.e., hepatitis, cirrhosis)

- Uncontrolled high blood pressure, history of labile hypertension, or history of poor
compliance with an antihypertensive regimen

- Chronic renal disease, i.e. Creatinine >1.5 x 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 Haemoglobin < 9 g/dL (patients may be transfused to
achieve Hb > 9 g/dL)

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

- 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

- Human immunodeficiency virus (HIV) infection,

- Prior enrollment into this study.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall response defined by RECIST criteria

Outcome Time Frame:

8 week response rate

Safety Issue:


Principal Investigator

Michael Weichenthal, MD

Investigator Role:

Study Director

Investigator Affiliation:

UK-SH Department of Dermatology


Germany: Federal Institute for Drugs and Medical Devices

Study ID:

UKSH A-105



Start Date:

December 2006

Completion Date:

Related Keywords:

  • Melanoma
  • Metastatic melanoma
  • anti angiogenetic treatment
  • Melanoma