| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage III BRAF V600 mutation-positive melanoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Malignant melanoma characterized by a mutation in the BRAF V600 gene |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10025650 |
| E.1.2 | Term | Malignant melanoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 assess whether an adapted AE- management algorithm for pyrexia will reduce the incidence of pyrexia related outcomes |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives for this study are:
1) To evaluate relapse-free survival (RFS) at 12 and 24 months
2) To evaluate overall survival (OS) rate at 12 and 24 months
3) To evaluate pyrexia
4) To evaluate the overall adverse events (AE) rate leading to permanent treatment discontinuation by 12 months
5) To evaluate (Health-Related Quality Of
Life ) HRQOL measures assessed using FACT-M
6) To evaluate overall safety |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• >18 years of age with Informed consent
• Signed informed consent must be obtained prior to
participation in the study.
• Completely resected (R0) histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] no more than 12 weeks before enrollment
• V600E/K mutation positive using a validated local test
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Subject has adequate bone marrow and organ function as defined by the following laboratory values without continuous supportive treatment (such as blood transfusion, coagulation factors and/or platelet infusion, or red/white blood cell growth factor administration) as assessed by laboratory for eligibility:
- Hematological
- Coagulation
- Renal
- Hepatic
- Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• Able to swallow and retain oral medication and must
not have any clinically significant gastrointestinal
abnormalities that may alter absorption such as
malabsorption syndrome or major resection of the
stomach or bowels
Other protocol-defined inclusion criteria may apply |
|
| E.4 | Principal exclusion criteria |
• Uveal or mucosal melanoma
• Evidence of metastatic disease including unresectable in-transit metastasis
• Received any prior adjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma
• Taken an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to enrollment.
• Current or expected use of a prohibited medications (other anticancer therapies, other investigational drugs, antiretroviral drugs, herbal remedies, and drugs that are strong inhibitors or inducers of CYP3A and CYP2C8).
• Non-melanoma related major surgery or significant traumatic injury ≤ 2 weeks prior to start of study treatment. Minor surgical procedures should be completed 7 days prior to start of study treatment
• Known immediate or delayed hypersensitivity
reaction or idiosyncrasy to drugs chemically related to
the study treatments, their excipients, and/or dimethyl
sulfoxide (DMSO)
• Subjects with known history for testing positive for
Human Immunodeficiency Virus (HIV)
• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.
• Cardiac or cardiac repolarization abnormality
• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy
• History of clinically significant or active interstitial lung disease or pneumonitis
• Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could interfere with the subject’s safety, obtaining
informed consent, or compliance with study procedures
• Women child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 4 months after stopping study treatment.
• Women who are nursing during dosing and for 4 months after stopping study treatment
• Male subjects (including those that have had a vasectomy) taking study treatment must use a condom during intercourse, and for 16 weeks after stopping treatment, and should not father a child during these periods
Other protocol-defined exclusion criteria may apply |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The composite rate of grade 3/4 pyrexia, hospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated patients. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
a) RFS is defined as the time from the first dose of the study medication to disease recurrence or death from any cause at 12 and 24 months
b)OS is defined as the time from the first dose of study medication to date of death due to any cause at 12 and 24 months
c) Frequency, number of episodes, duration, AE management (including concomitant medications and study treatment modifications) due to pyrexia
d) The proportion of patients in the study who permanently discontinued treatment due to any Adverse event by 12 months
e) Changes in the HRQOL from baseline will be assessed using by FACT-M questionnaire
f) Safety will be assessed by the frequency and severity of adverse events (AEs), serious AEs (SAEs) and laboratory abnormalities
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) 12 and 24 months
b) 12 and 24 months
c) 24 months
d) 12 months
e) 24 months
f) 24 months |
|
| 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 | 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 | 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 | No |
| 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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 131 |
| 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 | No |
| 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 |
| Argentina |
| Australia |
| Belgium |
| Brazil |
| Canada |
| Chile |
| Colombia |
| Czech Republic |
| Finland |
| France |
| Greece |
| Hungary |
| Israel |
| Italy |
| Japan |
| Latvia |
| Lithuania |
| Norway |
| Poland |
| Portugal |
| Russian Federation |
| Serbia |
| Slovakia |
| Slovenia |
| Spain |
| Sweden |
| Turkey |
| United Kingdom |
|
| 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
|
| Study completion is defined as 24 months after the first dose (Day 1) of the last subject enrolled, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator, or in the event of an early study termination decision, the date of that decision. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 4 |
| 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 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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