A study to test a new medication for patients with advanced or metastatic melanoma
- Conditions
- Advanced or metastatic melanomaCancer - Malignant melanoma
- Registration Number
- ACTRN12611000275965
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 297
1) Histologically confirmed, Stage III unresectable (Stage IIIc) or metastatic (Stage IV) cutaneous melanoma which is also determined to be BRAF V600E/K mutation-positive by the central laboratory.
2)Subjects may have received no prior treatment or up to one prior regimen of chemotherapy for advanced or metastatic melanoma. Prior treatment with immunotherapy (with the exception of prior ipilimumab, which is only allowed if given in the adjuvant setting), cytokine therapy, biological or vaccine regimen is permitted. Prior use of sorafenib is allowed.
3) Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
4) All prior treatment- related toxicities must be CTCAE (Version 4.0) Grade less than or equal to 1 (except alopecia) at the time of randomisation.
5)Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
1) Any prior use of:
a. BRAF inhibitors or MEK inhibitors
b. Ipilimumab in the advanced or metastatic setting
2) Subjects who have received dacarbazine or paclitaxel prior to randomization will not be eligible to receive the same chemotherapy as study medication.
3) Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy or immunotherapy within the last 21 days. Chemotherapy given daily or weekly without the potential for delayed toxicity within the last 14 days.
4) Administration of an investigational drug within 28 days or 5 half-lives, (whichever is shorter), prior to randomization – at least 14 days must have passed between the last dose of the prior investigational anti-cancer drug and randomization.
5)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 or successfully treated in situ carcinoma are eligible. Subjects with second malignancies that are indolent or definitively treated may be enrolled.
6) Any serious and/or unstable pre-existing medical (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures.
7) Known Human Immunodeficiency Virus, Hepatitis B Virus, or Hepatitis C Virus infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed).
8) Brain metastases with the following exceptions:
a. All known lesions must be previously treated with surgery or stereotactic radiosurgery
b. Brain lesion(s), if still present, must be confirmed stable (i.e. no increase in lesion size) for >=90 days prior to randomization (must be documented with two consecutive MRI or CT scans using contrast), and
c. Asymptomatic with no corticosteroids requirement for >= 30 days prior to randomization, and
d. No enzyme-inducing anticonvulsants for >= 30 days prior to randomization.
9) History or evidence of cardiovascular risk including any of the following:
a. QTcB >= 480 msec
b. History or evidence of current clinically significant uncontrolled arrhythmias. Exception: Subjects with controlled atrial fibrillation for >30 days prior to randomization are eligible
c. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
d. History or evidence of current >= Class II congestive heart failure as defined by New York Heart Association.
10) History of interstitial lung disease or pneumonitis.
11) History or current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):
a. History of RVO or CSR, or predisposing factors to RVO or CSR
b. Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:
c. Evidence of new optic disc cupping
d. Intraocular pressure > 21 mm Hg as measured by tonography.
12) Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, or excipients or to dimethyl sulfoxide (DMSO) or to Cremophor EL (polyoxyethylated castor oil).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) based on investigator assessments per RECIST 1.1 guidelines, defined as the time from randomisation until the earliest date of disease progression or death due to any cause.[The final analysis for PFS will be performed at the time at least 60 PFS events have occurred within each subpopulation of subjects with or without treatment with prior chemotherapy in the advanced or metastatic setting. Participants will be assessed for disease progression at weeks 6, 12, 21, 30 and then every 12 weeks.]
- Secondary Outcome Measures
Name Time Method