A Study to Assess APO866 for the Treatment of Advanced Melanoma

• Status: Completed
• Trial end date: 2009-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase II study is designed to determine the efficacy and safety of APO866 for the treatment of patients with advanced cutaneous melanoma. APO866 has shown to induce growth inhibition in cultures of human melanoma cells as well as in animal models with subcutaneously implanted melanoma tumors. APO866 was considered to be safe and well tolerated in a phase I study that treated 24 patients with advanced cancer. In that study one of the two patients with advanced melanoma had a stable disease for 5 months with size reduction of some lesions. APO866 is administered by intravenous infusion continuously for 96 hours that is repeated every 4 weeks. Patients will receive 3 cycles of treatment and the primary efficacy endpoint will be assessed at Week 16. Patients will be follow-up for 12 months.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Onxeo

Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis of melanoma

• Stage IV disease or stage III not amenable to surgery (AJCC, see Appendix A)

• Measurable disease, defined as at least 1 malignant lesion that could be accurately and serially measured in at least 1 dimension and for which the greatest diameter is > or = 10 mm as measured by spiral computed tomography (CT) scan or magnetic resonance imaging (MRI), or > or = 20 mm with conventional techniques. A caliper can be used for the measurement of superficial cutaneous metastases which are > or = 10 mm.

• Patients must be able to undergo either contrast-enhanced CT-scan or contrast-enhanced MRI scan for tumor assessment

• Only one previous systemic treatment (excluding prior systemic treatment as postoperative adjuvant therapy) is allowed and should have been terminated > 4 weeks before Study Day 1 (SD1).

• Lack of response or progression of disease after the most recent systemic therapy for advanced melanoma

• Patients must have recovered from the toxicity of any previously used treatment. All Adverse events of previous systemic treatment must have resolved to < grade I Common Terminology Criteria for Adverse Events (CTC v3.0, see Appendix)

• Eastern Cooperative Oncology Group (ECOG) Performance Status < 1 (see Appendix C)

• Age > 18 years, of either sex

• Female patients with childbearing potential must be using a hormonal contraceptive, intra uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study. Women of childbearing potential must have a negative serum or urinary human chorionic gonadotropin (hCG) pregnancy test within 7 days prior to Study Day 1 (SD1)

• Male patients, who are not surgically sterile, must use a condom with spermicide for the duration of the study and 3 months thereafter

• Have given written informed consent, prior to any study related procedure not part of the patient's normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria:

• Have participated in any other investigational study or received an experimental therapeutic procedure considered to interfere with the study in the 4 weeks preceding SD1

• History of brain metastases or leptomeningeal disease

• Bone-only metastatic disease

• Use of prohibited medication due to Cytochrome P450 3A4 (CYP3A4) metabolism of APO866, as specified in Section 6.6.2. concomitant use of these drugs will not be allowed during the study.

• Use of biphosphonate drug during the 30 days preceding the APO866 infusion and during the treatment period will not be allowed

• Uncontrolled medical conditions, requiring surgical or pharmacological treatment (exceptions must be approved by the Medical Responsible of the study).

• Serious concomitant disease (e.g. significant cardiac disease)

• History of second cancer that was treated with curative intent and in complete remission for < 5 years, with the exception of basal cell carcinoma or cervical cancer in situ

• Primary or acquired thrombocytopenia

• Inadequate bone marrow reserve: white blood cell (WBC) < 3.5x10^9/L, neutrophils < 1.0x10^9/L, thrombocytes < 100x10^9/L, Hb < 10.0 g/dL or coagulation abnormalities

• Inadequate liver function: total bilirubin > 1.5 x upper limit of normal values (ULN), aspartate aminotransferase (AST), Alanine Amino Transferase (ALT), or alkaline phosphatase > 2.5 x ULN

• Have inadequate renal function, defined by serum creatinine > 1.5x ULN

• Retinopathy, history of retinal laser surgery, or an ERG < 50% of normal

• Pregnant of lactating female

• Abuse of alcohol or other recreational drugs