E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027480 |
E.1.2 | Term | Metastatic malignant melanoma |
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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 |
The primary objective of this study is to compare progression-free survival and overall survival in the dacarbazine plus Genasense treatment group and the dacarbazine plus placebo treatment group. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to compare the 2 treatment groups with respect to the percentages of subjects with response and durable response, duration of response, and the safety of the 2 treatment regimens. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically confirmed diagnosis of melanoma 2. Progressive disease that is not surgically resectable, or metastatic Stage IV disease 3. LDH </= 0.8 x ULN 4. Chemotherapy naïve Note: Prior immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy is permitted. 5. Measurable disease defined as at least 1 tumor lesion that can be accurately and serially measured in at least 1 dimension (longest diameter to be recorded) and is >/= 20 mm with conventional techniques and >/= 10 mm with spiral CT, based on Response Evaluation Criteria in Solid Tumors (RECIST) Lesions that are considered nonmeasurable include: − Bone lesions − Ascites and pleural/pericardial effusions − Lymphangitis cutis/pulmonis − Abdominal masses not confirmed and not followed by imaging studies − Cystic lesions − Tumors treated by irradiation or intra-tumor injection therapy without progression in that area or measurable disease outside that area 6. ECOG performance status </= 1 7. At least 4 weeks and recovery from effects of prior surgery or other therapy, including immunotherapy, radiotherapy, or cytokine, biologic, or vaccine therapy 8. Adequate organ function, defined as: a. Absolute neutrophil count (ANC) ≥ 1500/mm3 b. Platelet count ≥ 100,000/mm3 c. Hemoglobin ≥ 11 g/dL without need for hematopoietic growth factor or transfusion support d. Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min e. Serum bilirubin ≤ 1.5 x ULN f. Aspartate aminotransferase (AST) ≤ 2.5 x ULN g. Alanine aminotransferase (ALT) ≤ 2.5 x ULN h. Alkaline phosphatase ≤ 2.5 x ULN i. Serum albumin ≥ 3.0 g/dL j. Prothrombin time (PT) ≤ 1.5 x ULN (or international normalized ratio [INR] ≤ 1.3) k. Partial thromboplastin time (PTT) ≤ 1.5 x ULN
Note: The Investigator should exercise clinical judgment when assessing organ function. For example, a laboratory test result may not meet the protocolspecified criterion because the subject has a stable coexisting condition,which, in the Investigator’s opinion, will not affect the subject’s participation in this study. The Investigator should contact the Genta Medical Monitor (see page 2 of the protocol for contact information) to discuss such cases. A subject may be included in the study based upon the Investigator's clinical judgement and/or discussion with the Genta Medical Monitor.
9. At least 18 years of age 10. Venous access adequate to maintain a 5-day continuous intravenous infusion 11. Ability to maintain an ambulatory infusion pump. 12. In women of childbearing potential (that is, all women except for those who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization), a negative serum pregnancy test within 7 days prior to randomization. 13. In subjects of childbearing potential (that is, all men and all women excluding women who are post menopause for > 1 year or who have a history of hysterectomy or surgical sterilization), agreement to use a highly effective form of contraception (ie, one that has a failure rate of < 1%) throughout the treatment phase of the study. |
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E.4 | Principal exclusion criteria |
1. Prior cytotoxic chemotherapy, including regional perfusion, or prior Genasense treatment 2. Need for other anticancer treatment (such as chemotherapy, radiation, or biologic or investigational therapies) while receiving protocol therapy in this study 3. Primary ocular or mucosal melanoma 4. Bone-only metastatic disease 5. History or presence of brain metastasis or leptomeningeal disease 6. History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 or more years) 7. Significant medical disease other than cancer, such as: uncontrolled congestive heart failure; active symptoms of coronary artery disease (defined as uncontrolled arrhythmias or recurrent chest pain despite prophylactic medication); New York Heart Association Class III or IV disease; cardiovascular signs and symptoms >/= Grade 2 by common toxicity criteria (CTC) during the 4-week period prior to initiation of protocol therapy; uncontrolled seizure disorder; history of chronic hepatitis or cirrhosis; active infection; uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment with an average dose >/= 20 mg/day of prednisone (or equivalent); requirement for concurrent immunosuppressive drug(s); active autoimmune disease 8. Organ allograft 9. Known human immunodeficiency virus infection 10. Pregnancy or lactation 11. Known hypersensitivity to dacarbazine or phosphorothioate-containing oligonucleotides 12. Use of any experimental therapy within 3 weeks prior to screening evaluations |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are progression-free survival and overall survival. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 56 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of trial is defined as when the last patient completes 24 months after randomisation. The efficacy endpoints rely on 'time to event' (either progression or death). This means that the last patient, last visit is not an appropriate definition for the end of the trial. The period of follow-up has been set at 2 years based on the natural history of the disease. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |