Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib Plus GDC-0973 in Previously Untreated BRAF^600-Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Brief Summary: To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by progression-free survival (PFS), assessed by the study site investigator.


Options:
A: Inclusion Criteria:

* Patients from both sexes aged over 18 years and operable
* Presenting with LM of the face, the neck, or the scalp (in case of hairless scalp only) histologically confirmed by biopsy
* Patients presenting with a primitive lesion, of a surface ≥ to 1cm² and ≤ to 20cm², with the possibility of graft or flap reconstruction
* LM previously untreated by surgery
* LM without prior treatment with liquid nitrogen or any other local treatment within 3 months
* ECOG ≤ 2
* Leucocytes ≥ 3,000/mm³
* Neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Haemoglobin ≥ 9.0g/dL
* Absence of severe evolutive infection
* Absence of known HIV infection
* Absence of corticotherapy and treatment by immunosuppressive agents
* Absence of excoriation and scarring biopsy prior to application of study treatment
* Membership to a social security insurance scheme.
* Negative pregnancy test conducted during the inclusion consultation for non-menopausal women.
* Effective contraception for patients of childbearing age
* Signed informed consent

Exclusion Criteria:

* LM located on the eyelids are excluded, together with LM in anatomic sites other than the face, the neck or the scalp
* Melanomas other than LM
* Invasive LM
* LM with a surface area \< to 1cm² or \> to 20cm²
* LM of which the macroscopic contours cannot be defined
* Patients who are allergic to imiquimod excipient (eg hydroxybenzoate)
* Patients with a hypersensitivity to active substances or to any of the excipients of the placebo (for example propyl parahydroxybenzoate)
* Patients treated by immunosuppressive agents, immunomodulators, cytotoxic agents or corticosteroids (local and systemic) during the 4-week period prior to the selection visit
* Patients with auto-immune disease (except vitiligo) or transplant patients
* Cutaneous reconstruction not possible
* Presence of associated evolutive neoplasia since less than 5 years (with the exception of basal cell carcinoma, Bowen's carcinoma and carcinoma in situ of the cervix)
* Patient refusing surgery under local or general anaesthesia
* Pregnant women
B: Inclusion Criteria:

* Diagnosed with malignant melanoma
* Measurable unresectable Stage III or IV melanoma
* HLA-A\*0201 positive
* Previous treatment with \& failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
* At least 4 weeks since prior treatment
* Negative pregnancy
* Life expectancy greater than 4 months
* Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
* Required lab values
* Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative

Exclusion Criteria:

* Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
* Ocular melanoma
* Active, untreated central nervous system (CNS) metastasis
* Prior treatment with MDX-010 (anti-CTLA4) antibody
* Prior treatment with any cancer therapeutic vaccine
* Active autoimmune disease or history of autoimmune disease
* Pregnancy or nursing
* Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
* Underlying medical conditions deemed hazardous if treated with study drug
* Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
* Unable to provide informed consent
C: Inclusion Criteria:

* Adults at least 18 years of age
* Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E)
* Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed.
* Has measurable disease according to RECIST 1.1 criteria.
* Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
* Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
* Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
* Must have adequate organ function.
* Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

Exclusion Criteria:

* Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
* Evidence of active central nervous system (CNS) disease.
* Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor.
* A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
* History of Human Immunodeficiency Virus (HIV) infection.
* Certain cardiac abnormalities
D: Inclusion Criteria:

* Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
* Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
* Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
* Measurable disease per RECIST v1.1
* Eastern Clinical Oncology Group performance status of 0 or 1
* Consent to provide archival for biomarker analyses
* Consent to undergo tumor biopsies for biomarker analyses
* Life expectancy greater than or equal to (≥) 12 weeks
* Adequate hematologic and end organ function

Exclusion Criteria:

* History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
* Palliative radiotherapy within 14 days prior to the first dose of study treatment
* Major surgery or traumatic injury within 14 days prior to first dose of study treatment
* Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
* History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
* Uncontrolled glaucoma with intraocular pressure
* Serum cholesterol ≥ Grade 2
* Hypertriglyceridemia ≥ Grade 2
* Hyperglycemia (fasting) ≥ Grade 2
* History of clinically significant cardiac dysfunction
* Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:

  1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND
  2. There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
* Current severe, uncontrolled systemic disease
* History of malabsorption or other condition that would interfere with absorption of study drugs
* Pregnant, lactating, or breast feeding women

Answer: D