E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with histologically confirmed metastatic melanoma |
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E.1.1.1 | Medical condition in easily understood language |
Patients with metastatic melanoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
To evaluate response rate according to the RECIST v.1.1 criteria. Response rate will be evaluated separately for each treatment arm. |
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E.2.2 | Secondary objectives of the trial |
To evalute progression-free survival, Toxicity and safety of treatment, Overall survival, Progression-free survival at 6 months, Time to brain metastases or their progression, QOL (15-D questionnaire) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria:
1. Signed informed consent obtained prior to any study specific screening procedures
2. Histologically confirmed inoperable stage III or stage IV metastatic melanoma
3. Performance status: WHO 0-2
4. Measurable or evaluable disease according to RECIST 1.1
5. BRAF mutation status should be analysed; if technically not possible the patient is treated as BRAF negative
6. Age 18 years of age
7. Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study
8. Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment
9. Previous adjuvant therapy is allowed
10. Previous immunotherapy in the metastatic setting is allowed
11. Patients with previously treated, asymptomatic brain metastases are allowed
12. Neutrophils 1’200/l, Platelets 100’000/l, Alanine amino transferase 2.5 Upper limit of normal (ULN) (< 5 ULN if liver metastases), Alkaline phosphatase 2.5 ULN (< 5 ULN if liver metastases), Serum bilirubin 1.5 ULN, Serum Creatinine 1.5 ULN
13. Patient must be able to comply with the protocol
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E.4 | Principal exclusion criteria |
Exclusion criteria:
1. Prior systemic treatment for metastatic melanoma (except for immunotherapy)
2. Symptomatic brain metastases not responding to corticosteroids and radiotherapy
3. Presence of active gastrointestinal disease or condition that will interfere significantly with the intake of drugs
4. Presence of malignancy other than cutaneous metastatic melanoma (Stage IV) within 5 years of study enrollment except for curatively treated basal and squamous cell carcinoma of the skin or In-situ carcinoma of the cervix
5. Corrected QT (QTc) interval 500 ms.
6. Uncontrolled medical conditions (i.e, diabetes mellitus, heart disorders, hypertension, etc), psychological, social, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
7. Pregnant or lactating females
8. Non-evaluable disease
9. Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk for treatment complications
10. Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial
11. Previous chemotherapy for metastatic melanoma
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E.5 End points |
E.5.1 | Primary end point(s) |
Response Rate according to RECIST 1.1 criteria. Response rate will be evaluated separately for each treatment arm.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
response rate: RECIST 1.1 (time frame: 2 year) |
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E.5.2 | Secondary end point(s) |
• Progression Free Survival (overall and at 6 months) (both progression after chemotherapy (PDct) and PD)
• Overall Survival (defined as the time period from the start of therapy to death)
• Time to brain metastases or their progression
• QOL (15-D questionnaire)
- Safety assessment will consist of evaluating laboratory parameters and recording adverse events according to NCI CTCAE v 4.0 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- Safety: Incidence of adverse events (time frame: 2 year) |
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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) | 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 | No |
E.8.1.1 | Randomised | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 study will be continued 12 months after the last patient’s last visit (LPLV). In addition, the sponsor (Finnish Melanoma Group) will evaluate the safety and toxicity of treatments continuously in order to decide the study continuation. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |