PTK/ZK in Disseminated Malignant Melanoma

This study has suspended participant recruitment.
(Substance was withdrawn from further development.)
Sponsor:
Information provided by:
University of Schleswig-Holstein
ClinicalTrials.gov Identifier:
NCT00615160
First received: January 31, 2008
Last updated: January 11, 2011
Last verified: December 2007
  Purpose

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


Condition Intervention Phase
Melanoma
Drug: PTK787/ZK 222584
Drug: Dacarbazine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Randomized, Parallel-Group Trial on PTK-ZK With or Without DTIC in Patients With Non-resectable Metastatic Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by University of Schleswig-Holstein:

Primary Outcome Measures:
  • Overall response defined by RECIST criteria [ Time Frame: 8 week response rate ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity and safety [ Time Frame: continuously ] [ Designated as safety issue: Yes ]
  • Tumor control as defined by the number of patients with objective tumor response or tumor stabilization according to RECIST criteria [ Time Frame: Best response during time of treatment ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Time of progression ] [ Designated as safety issue: No ]
  • Quality of life (EORTC QLQ C30) [ Time Frame: During active treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2006
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
PTK787/ZK 222584 (PTK-ZK) taken orally with a daily flat dose of 1250 mg on days 1 to 28 (= 1 cycle)
Drug: PTK787/ZK 222584
PTK-ZK capsules taken orally with a daily flat dose of 1250 mg
Experimental: B
combined treatment with DTIC 850 mg/m² on day 1 + PTK-ZK 1250 mg flat dose on days 1 to 28
Drug: PTK787/ZK 222584
PTK-ZK capsules taken orally with a daily flat dose of 1250 mg
Drug: Dacarbazine
Dacarbazine 850 mg/m² on day 1 q4w
Other Name: DTIC

Detailed Description:

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 protocol,
  • 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 treatment.
  • 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 immunotherapy
  • 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 medication
  • 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 disorder
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00615160

Locations
Germany
Dpt. of Dermatology, University of Essen
Essen, Germany, D-45122
Dpt. of Dermatology, University of Frankfurt
Frankfurt/Main, Germany, D-60590
Dpt. of Dermatology; UK-SH Campus Kiel, Germany
Kiel, Germany, D-24105
Dpt. of Dermatology, University of Cologne
Koeln, Germany, D-50937
Sponsors and Collaborators
University of Schleswig-Holstein
Investigators
Study Director: Michael Weichenthal, MD UK-SH Department of Dermatology
  More Information

No publications provided

Responsible Party: Michael Weichenthal MD, University Hospital Schleswig-Holstein
ClinicalTrials.gov Identifier: NCT00615160     History of Changes
Other Study ID Numbers: UKSH A-105, EudraCT No. 2005-002192-32
Study First Received: January 31, 2008
Last Updated: January 11, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Schleswig-Holstein:
Metastatic melanoma
anti angiogenetic treatment

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Dacarbazine
Vatalanib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014