Multicentre, Dose Finding, Ph II,CP-4055 in Comb. With Sorafenib - Patients With Metastatic Malignant Melanoma

• • Time to progression [ Time Frame: October 2008 ] [ Designated as safety issue: No ]
• • Duration of tumour response [ Time Frame: October 2008 ] [ Designated as safety issue: No ]
• • Safety and tolerability of treatment [ Time Frame: October 2008 ] [ Designated as safety issue: Yes ]

• • Time to progression
• • Duration of tumour response
• • Safety and tolerability of treatment

Patients with metastatic malignant melanoma will receive CP-4055 200 mg/m2/day intravenously (IV) on Day 1-5 every four weeks and sorafenib 400 mg b.i.d. (twice daily) every day until complete response or disease worsening/progressing.

This is a multicentre clinical study conducted in the USA and in Europe. It is an open label study designed to investigate objective tumor response, the time to progression (TTP) and the duration of tumor response in patients with metastatic malignant melanoma when treated with CP-4055 in combination with sorafenib (Nexavar®). The safety and tolerability of the treatment will also be assessed.

• Drug: CP-4055
  CP-4055 5mg/mL for infusion, dose: 200 mg/m2/day, schedule d1-5 q4w, 30 minutes IV infusion
  Other Name: ELACYT (TM)
• Drug: Sorafenib (Nexavar)
  Sorafenib 200 mg tablets, dose: 400 mg/day, daily dosing
  Other Name: Nexavar

Inclusion Criteria:

1. Patients with histological or cytological confirmed stage IV or unresectable stage III non-ocular malignant melanoma who have or have not undergone prior chemotherapy for the treatment of melanoma
2. Measurable disease according to Response Criteria In Solid Tumors (RECIST)
3. Performance Status 0 - 1 according to ECOG (Eastern Cooperative Oncology Group) Performance Status
4. Age 18 years or more
5. Life expectancy > 3 months
6. Signed informed consent
7. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study
8. Male and female patients must use acceptable contraceptive methods for the duration of time on study, and males also for 3 months after the last CP-4055 dose
9. Adequate haematological and biological functions

Exclusion Criteria:

1. Known brain metastases
2. Diagnosis of ocular malignant melanoma
3. Radiotherapy to more than 30 % of bone marrow
4. Participation in another therapeutic clinical study within 30 days of enrolment or during this clinical study

5. Requirement of concomitant treatment with a non-permitted medication:

   • Alternative drugs
   • High doses of vitamins
6. History of allergic reactions to ara-C or egg
7. History of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib
8. Presence of any serious concomitant systemic disorders incompatible with the clinical study (e.g. uncontrolled inter-current illness including ongoing or active infection)
9. Presence of any significant central nervous system or psychiatric disorder(s) that would hamper the patient's compliance
10. Pregnancy, breastfeeding or absence of adequate contraception for both male and female fertile patients
11. Known positive status for HIV and/or hepatitis B or C
12. Drug and/or alcohol abuse
13. Any reason why, in the investigator's opinion, the patient should not participate
14. Prior treatment with CP-4055 and/or sorafenib

15. Significant history of cardiac disease, including any of the following:

    • Uncontrolled hypertension
    • Unstable angina pectoris
    • Congestive heart failure
    • Myocardial infarction within the past 6 months
    • Unstable ventricular arrhythmia
    • Other cardiac arrhythmia
16. Condition that impairs ability to swallow pills
17. Tendency of bleeding