E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Second Line metastatic melanoma |
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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 | 10027481 |
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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 |
To compare the overall survival (OS) of patients who have received one prior regimen of dacarbazine or temozolomide-based chemotherapy for metastatic melanoma when treated with either tasisulam or paclitaxel. |
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E.2.2 | Secondary objectives of the trial |
to compare the following between treatment arms: progression-free survival (PFS) duration of response (DoR) deterioration in the FACT-M TOI score objective tumor response rate therapeutic benefit rate (TBR) measures of relative safety, including quantitative and qualitative laboratory and non-laboratory toxicities health outcome measures, including the quality-adjusted life years (QALYs) gained, time to worsening of health related quality of life (TWQ), and measures of the patient s well-being and symptoms. Translational Research (TR): to evaluate the treatment-specific and treatment-independent effects of BRAF and c-Kit mutational status on measures of clinical efficacy, including OS, PFS, DoR, and response to evaluate the treatment-specific effects of genetic markers, including but not limited to DMET genes such as CYP2C19 and CYP2C9, on measures of clinical efficacy and toxicity. to assess other exploratory biomarkers relevant to tasisulam and paclitaxel |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ALTRI SOTTOSTUDI: Lo studio di farmacogenetica e` parte del protocollo. Gli obiettivi di farmacocinetica e di qualita` della vita sono parti integranti del protocollo di studio principale.
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E.3 | Principal inclusion criteria |
[1] Have a histologic and/or cytologic diagnosis of metastatic melanoma (Stage IV). [2] Have the presence of evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST version1.0). [3] Are at least 18 years of age. [4] Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Scale (see Attachment JZAO.4). [5] Have progressed after 1 previous systemic treatment regimen
containing dacarbazine or temozolomide for metastatic melanoma. [6] Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, or other investigational therapy for at least 30 days (45 days for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). Whole-brain radiation must have been completed 90 days before starting study therapy. [7] Have adequate organ function including: Bone Marrow Reserve: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment, platelets ≥ 100 x 109/L, and hemoglobin ≥ 8 g/dL (transfusions are not allowed to reach 8 g/dL prior to enrollment). Hepatic: Bilirubin ≤ 1.5 times the upper limit of normal (ULN). Alkaline phosphatase and transaminases (ALT and AST) ≤5 times ULN. Renal: Serum creatinine at or below the ULN. No known active renal disease. [8] Have a serum albumin level ≥ 3.0 g/dL or ≥ 30 g/L. [9]Males and females with reproductive potential should use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug. [10] Females with child-bearing potential must have had a negative serum pregnancy test ≤ 7 days prior to the first dose of study drug. |
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E.4 | Principal exclusion criteria |
14] Are currently enrolled in, or discontinued within the last 30 days from,a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. 15] Have received ≥ 2 previous chemotherapy-containing systemic treatment regimens for metastatic melanoma. An immunotherapy or antibody-based regimen [including biologic agents and vaccinationbased treatments], or treatment with a targeted agent (e.g BRAF or c- Kit inhibitor, is not counted as a prior treatment regimen for determining study eligibility, unless either was combined with a cytotoxic drug). 16] Any previous treatment with paclitaxel or a paclitaxel-containing regimen for metastatic melanoma. 17] Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of study entry. Patients with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out occult brain metastasis. Patients with a history of a solitary CNS metastasis previously treated with curative intent (e.g., stereotactic radiation or surgery) and not requiring steroids are eligible. 18] Have serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator). 19] Have a second primary malignancy that could affect compliance with the protocol or interpretation of the results. NOTE: Patients with adequately treated carcinoma of the skin (non-melanoma) and patients with a prior history of malignancy who have been disease-free for more than 2 years are eligible. 20] Have serious preexisting medical conditions (at the investigators discretion). 21] Are receiving warfarin. 22] Have previously completed or withdrawn from this study or any other study investigating tasisulam. 23] Have a known hypersensitivity to paclitaxel or Cremophor EL (polyoxyethylated castor oil). 24] Are pregnant or lactating. 25] Have primary ocular or mucosal melanoma. 26] Have received a recent (within 30 days before enrollment) or are receiving concurrent yellow fever vaccination. 27] Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies(HCAb). |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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`la data dell`ultima visita o dell`ultima procedura programmata, indicata tra le procedure dello studio per l`ultimo paziente in corso nello studio. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |