A study to test two investigational drugs, dabrafenib and trametinib, for treating melanoma
- Conditions
- Cutaneous melanoma - aggressive form of skin cancers.MedDRA version: 20.0Level: PTClassification code 10040808Term: Skin cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-006087-49-GB
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 423
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 (metastic), and determined to be BRAF V600E/K mutation-positive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory.
Subjects with ocular or mucosal melanoma are not eligible.
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 protocol for
the definition of a measureable lesion.
5. All prior anti-cancer treatment-related toxicities (except alopecia) and laboratory values must be = Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 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 protocol, throughout the treatment period, and for 4 months after the last dose of study treatment.
8. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Adequate baseline organ function as defined in Table 2 (page 25 of 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 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75
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.
6. History of another malignancy.
Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer, and/or subjects with indolent second malignancies are eligible.
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 by the New York Heart Association (NYHA) guidelines (Appendix 4 of
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