A study to test two investigational drugs, dabrafenib and trametinib, in combination together for treating a specific type of melanoma compared to another drug, vemurafenib that is approved for treatingthe same type of melanoma.
- Conditions
- Metastatic melanomaMedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-006088-23-NL
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 704
Subjects eligible for enrolment in the study must meet all of the following criteria:
1. = 18 years of age.
2. Signed written informed consent.
3. Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE:G120011). The IUO assay is currently approved (THxID BRAF assay). The assay will be tested in a central reference laboratory. Subjects with ocular or mucosal melanoma are not elegible.
4. Measurable disease (i.e., present with at least one measurable lesion per RECIST, version 1.1. Refer to Section 7.2.3.1 of the Protocol for the definition of a measurable lesion.
5. All prior anti-cancer treatment-related toxicities (except alopecia) must be = Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.0; National Cancer Institute ( NCI) 2009) at the time of randomization.
6. 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.
7. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to use effective contraception, as defined in Section 7.3.3 of the Protocol, throughout the treatment period, and for 6 months after the last dose of study treatment.
Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 7.3.3 of the protocol from 14 days prior to administration of the first dose of study treatment, throughout the treatment period, and for 2 months after the last dose of study treatment.
8. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 [Oken 1982]. Refer to Appendix 1 of the protocol for details.
9. Adequate baseline organ function as defined in Table 2 (see inclusion criteria within the Protocol).
10. Subjects enrolled in France: In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 541
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 153
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Prior treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or a MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119).
2. Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Note: Ipilimumab treatment must end at least 8 weeks prior to randomization.)
3. Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomization.
4. Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to randomization.
5. Current use of a prohibited medication as described in Section 6.2 of Protocol.
6. History of another malignancy.
Exception: Subjects who have been disease-free for 3 years, (i.e. subjects with second malignancies that are indolent or definitively treated at least 3 years ago) or subjects with a history of completely resected non-melanoma skin cancer.
7. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject’s safety, obtaining informed consent, or compliance with study procedures.
8. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed).
9. A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.
10. Brain metastasis are excluded unless:
a. All known lesions were previously treated with surgery or stereotactic surgery (whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery), AND
b. Brain lesion(s), if still present, must be confirmed stable (i.e., no increase in lesion size) for = 12 weeks prior to randomization (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast, AND
c. Asymptomatic with no corticosteroid requirements for = 4 weeks prior to randomization, AND
d. No enzyme inducing anticonvulsants for = 4 weeks prior to randomization
In addition, for subjects that had brain metastases but currently have no evidence of disease (NED), NED for =12 weeks is required and must be confirmed by two consecutive scans, separated by =6 weeks, prior to randomization.
11. A history or evidence of cardiovascular risk including any of the following:
a. LVEF < LLN
b. A QT interval corrected for heart rate using the Bazett’s formula (QTcB; Appendix 3) = 480 msec;
c. A history or evidence of current clinically significant uncontrolled arrhythmias;
Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible.
d. A history (within 6 months prior to randomization) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty;
e. A history or evidence of current = Class II congestive heart failure as defined
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method