E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Melanoma Stage IV |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10025671 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the safety and efficacy of CNTO 95, alone and in combination with dacarbazine (DTIC), as compared to DTIC alone. |
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E.2.2 | Secondary objectives of the trial |
To assess the pharmacokinetics and pharmacodynamics of CNTO 95 when used alone or in combination with DTIC. Exploratory pharmacogenomics will be evaluated in consenting subjects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female ≥ 18 years
- Provide signed informed consent(s) prior to any study specific-procedures and agree to comply with all protocol-specified procedures
- Histologically confirmed melanoma
- AJCC Stage IV melanoma
- Radiographically measurable disease (at least 1 measurable lesion as defined by RECIST) or measurable skin lesion
- Previously untreated for metastatic melanoma by chemotherapy
- ECOG performance status ≤ 2
- Life expectancy of ≥ 12 weeks
- At least 4 weeks from prior major surgery to date of first study agent administration. Subjects must have recovered or stabilized from prior surgery
- Women of childbearing potential must be using adequate birth control measures (eg, oral contraceptives, complete abstinence, intrauterine device, barrier method with spermicide, or surgical sterilization) and not be breast-feeding, and men must be using barrier contraception with spermicide. Subjects must agree to continue such precautions for 6 months after the last administration of study agent. Women of childbearing potential must test negative for pregnancy at screening with a b-HCG serum pregnancy test
- Adequate bone marrow, liver, and renal function: a. Neutrophils ≥ 1500/mm3 (or ≥ 1.5 billion/L) b. Platelets ≥ 100,000/mm3 (or ≥ 100 billion/L) c. Hemoglobin ≥ 10.0g/dL (or ≥ 100 g/L) d. Bilirubin ≤ 1.5 x upper limit of normal (ULN) e. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 4.0 x ULN with liver metastases) f. Serum creatinine ≤ 1.5 x ULN g. Prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT) within normal range |
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E.4 | Principal exclusion criteria |
- Prior chemotherapy for melanoma
- Received any investigational drug, systemic cancer therapy, or generalized radiation therapy within 30 days of date of first study agent administration
- History of receiving murine or human/murine recombination products of human alpha-v integrins
- History of anaphylaxis or severe allergic reaction(s) to mouse proteins or any components of CNTO 95
- Clinically important active infection
- Known human immunodeficiency virus (HIV) positively
- Presence of nonmeasurable lesions only (ie, bone metastases or malignant effusions)
- CNS metastases
- Prior radiation to target lesions (palliative radiation therapy to nontarget lesions is permitted)
- Concomitant or prior malignancy (other than the one under study) except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other cancer for which the subject has been disease-free for ≥ 5 years
- Concurrent immunotherapy, biotherapy, radiotherapy, chemotherapy, investigational therapy, or steroid therapy (except for topical and inhaled steroids, or unless clinically indicated [eg, reactions to IV contrast, allergic reactions that develop during the study, sever nausea and vomiting]) if planned to be given concomitantly
- Requires concurrent anticoagulation therapy (except for low dose prophylactic warfarin)
- History of bleeding diathesis
- Recurrent deep vein thrombosis (DVT) or DVT within the 6 months preceding treatment assignment/randomization
- Planned surgery (except for minor surgical procedures) during study period
- History of uveitis
- Any medical condition that, in the opinion of the investigator, may compromise the compliance of the subject to receive study treatment
- Requires hematopoietic growth factors or transfusion of blood products to meet eligibility criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival defined as the time interval from the date of randomization to the date of initial documented disease progression on study or date of death. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |