Saves the questions and what to expect into your notes, next to the visit they belong to.
Keep this study
Lead
Technische Universität Dresden
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
Signed informed consent
Female and male patients ≥ 18 years of age
Histologically confirmed metastatic melanoma (stage IV, per AJCC staging), carrying BRAF V600-mutation
Performed SRS 14 ±7 days before baseline using a harmonized protocol in patients with at least one measurable intracranial target lesion for which the following criteria are met:
* Previously untreated (Lesions in previously irradiated area should not be selected)
* Largest diameter of ≥ 0.5 but ≤ 4 cm as determined by contrast-enhanced MRI and
* ≤ 10 brain metastases
ECOG performance status 0 - 2
Life expectancy ≥ 12 weeks
Adequate bone marrow function as indicated by the following:
* ANC ≥ 1500/µL,
* Platelets ≥ 100,000/µL and
* Hemoglobin ≥ 9 g/dL
Adequate renal function, as indicated by creatinine ≤ 1.5 x ULN
Adequate liver function, as indicated by bilirubin \< 1.5 x ULN and AST and ALT \< 3 x ULN (documented liver metastases: AST and ALT \< 5 x ULN)
Adequate coagulation within 28 days prior to baseline visit
* Patients without therapeutic anticoagulation: INR or aPTT ≤ 1.5 x ULN
Symptomatic brain metastases requiring immediate local interventions such as neurosurgery or radiosurgery
Leptomeningeal disease (also synchronous with brain metastases)
Prior therapy with BRAF or MEK inhibitors within 12 weeks prior to baseline visit (prior therapies for metastatic melanoma including chemo-, cytokine-, immuno-, biological and vaccine-therapy will be al-lowed) A period of at least 6 weeks must be observed between the last dose of ipilimumab and the first administration of the study treatments. Prior treatment with anti-programmed cell death (PD)-1 or anti-PD ligand 1 (PD-L1) is allowed.
Prior whole brain irradiation (Patients with prior local therapy of brain metas-tases are eligible)
Patients receiving therapeutic steroids are not stable on corticoster-oids 2 weeks before SRS
Active and uncontrolled infection
Known HIV infection or active HBV or HCV infection
* Active HBV infection (chronic and acute), defined as having a posi-tive hepatitis B surface antigen (HBsAg) test at screening (past or resolved HBV infection, defined as negative HBsAg test and a posi-tive total hepatitis B core antibody test at screening, are eligible)
* Active HCV infection, defined as positive HCV antibody test and positive HCV RNA test at screening
Intracranial radiation therapy within 14 days prior to SRS
Extracranial radiation therapy within the last 14 days prior to baseline visit
Treatment with strong CYP3A4/5 inhibitors (e.g. ketoconazole) and inducers (e.g. phenytoin, carbamazepine). (anticonvulsant levetiracetam is allowed; patient should be stable on levetiracetam for 2 weeks)
Unresolved toxicity of National Cancer Institute Common Terminology Crite-ria for Adverse Events, version 4.0 (NCI v4.0) \[NCI, 2009\] Grade 2 or higher from previous anti-cancer therapy, except alopecia.
Conditions that will interfere significantly with the absorption of drugs (e.g. Colitis ulcerosa)
Inability to undergo MRI secondary to:
* Metal,
* Claustrophobia, or
* Gadolinium contrast allergy
Previous malignancies active within the last 3 years, with the exception of locally curable cancers that have been treated to complete remis-sion or untreated stage I chronic lymphoid leukemia.
Unwillingness or inability to comply with study and follow-up procedures
Known hypersensitivity to any of the excipients of cobimetinib and vemuraf-enib
The following foods/supplements are prohibited at least 7 days prior to initia-tion of and during study treatment:
* St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer)
* Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor)
Patient is included in another interventional trial
Use of any investigational or non-registered product within 4 weeks prior to baseline visit
Woman of childbearing age with the exception they meet at least one of the following criteria:
* Post-menopausal,
* Sterilization,
* Consistently \& correct application of contraceptives (Pearl Index \< 1%),
* sexual abstinence, or
* vasectomy of the partner
Pregnant or lactating women
History, risk factor or retinal pathology that increases the risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR): evidence of retinal pathology that is considered a risk factor for RVO or CSR, or a history of retinal detachment, central serous chorioretinopathy or reti-nal vein thrombosis. The risk factors for RVO are listed below:
* Uncontrolled glaucoma with intraocular pressures \> 21 mm Hg,
