Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multi-center, Randomized, Double-Blind, Two-Arm, Phase III Study in Patients With Untreated Stage III (Unresectable) or IV Melanoma Receiving Dacarbazine Plus 10 mg/kg Ipilimumab (MDX-010) vs. Dacarbazine With Placebo
Brief Summary: The purpose of this clinical research study is to examine the safety and effectiveness (how well the drug works) of two different treatments for patients with melanoma. One treatment is an investigational compound (a drug that is not currently approved by the United States Food and Drug Administration \[FDA\]), know as Ipilimumab (also known as MDX-010 or BMS-734016) together with an approved chemotherapy drug called Dacarbazine


Options:
A: Key Inclusion Criteria:

* \>= 18 years of age
* Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma
* Measurable disease according to RECIST 1.1
* Women of childbearing potential with negative serum pregnancy test prior to randomisation
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Adequate baseline organ function

Key Exclusion Criteria:

* Any prior use of a BRAF or MEK inhibitor
* Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed
* History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer)
* Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed)
* Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for \>= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for \>= 12 weeks, and are asymptomatic with no corticosteroid requirements for \>= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for \>= 4 weeks prior to randomisation
* History or evidence of cardiovascular risk (LVEF \< LLN; QTcB \>= 480 msec; blood pressure or systolic \>=140 mmHg or diastolic \>= 90 mmHg which cannot be controlled by anti-hypertensive therapy)
* History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
B: Inclusion Criteria:

* Men and women, at least 18 years of age
* ECOG performance status 0 or 1
* Histologic diagnosis of melanoma staged:
* Tx or T1-4 and
* N1b, or N2b, or N2c, or N3
* M 0 that may present as any of the following groups:
* Primary melanoma with clinically apparent regional lymph node metastases, biopsy confirmed
* Clinically detected recurrence of melanoma at the proximal regional lymph node(s) basin, biopsy confirmed
* Clinically or histologically detected primary melanoma involving multiple regional nodal groups, biopsy confirmed
* Clinically detected single site of nodal metastatic melanoma arising from an unknown primary, biopsy confirmed
* Patients with intransit or satellite metastases with or without lymph node involvement are allowed if considered surgically resectable at baseline by the treating medical oncologist and surgical oncologist.

NOTE: All patients must be determined to be surgically resectable at baseline to be eligible for this neoadjuvant study.

* Patients must undergo biopsy (punch) or open biopsy (if done as part of a clinically indicated baseline diagnostic procedure) within 14 days of entry into the study. Lymphadenectomy/definitive surgery will be performed after at least 2 and generally not longer than 4 weeks of induction HDI-ipilimumab therapy. Additional delays for definitive lymphadenectomy/surgery are allowed if clinically indicated while awaiting the resolution of potential adverse events from HDI-ipilimumab therapy.
* Patients must have been evaluated by standard-of-care full body imaging studies (CT, PET-CT or MRI) as part of the initial clinical work-up at baseline (no more than 4 weeks prior to study enrollment) and after completion of induction HDI-ipilimumab (at 6-8 weeks after the first dose of ipilimumab/HDI and prior to the definitive lymphadenectomy procedure).
* Required values for initial laboratory tests:
* WBC ≥ 3000/uL
* ANC ≥ 1500/uL
* Platelets ≥ 100 x 103/uL
* Hemoglobin ≥ 10 g/dL
* Creatinine ≤ 1.8 mg/dL
* AST/ALT ≤ 2.5 x ULN
* Bilirubin ≤ 1.5 ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
* No active or chronic infection with HIV, Hepatitis B, or Hepatitis C

Exclusion Criteria:

* Clinical, radiological/laboratory, or pathological evidence of distant metastatic disease.
* Evidence of soft tissue involvement by gross extranodal extension of tumor manifest by fixation to the fascia, or matting of nodal tissue that would compromise surgical resection as determined by the surgical oncologist.
* History of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
* Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
* Autoimmune disease exclusions: a history of inflammatory bowel disease, a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
* Any underlying medical or psychiatric condition, which in the opinion of the Investigator/Sub-Investigator will make the administration of ipilimumab or HDI hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
* Underlying heart conditions if deemed ineligible for surgery by cardiology consult.
* Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
* Prior treatment with ipilimumab or CD137 agonist or CTLA-4 inhibitor or agonist.
* Prior radiotherapy, chemotherapy, including infusion or perfusion therapy for current disease or any immunotherapy including tumor vaccines, interferon-alfa, interleukins, levamisole or other biologic response modifiers within the past 4 weeks.
* Concomitant therapy with any of the following: IL 2 or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids; unless discontinued ≥ 4 weeks. A history of occasional use of steroid inhalers is allowed.
* Women of childbearing potential (who:
* Are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
* Have a positive pregnancy test at baseline, or
* Are pregnant or breastfeeding.
C: Inclusion Criteria:

* Informed Consent
* Measurable Disease
* Eastern Cooperative Oncology Group (ECOG) 0 or 1
* Lab / imaging requirements
* Neg for Human Immunodeficiency Virus (HIV), Hepatitis B (HepB), C
* Men and Women \> 18 years (16 were allowable)
* Prior therapy restriction (adjuvant only)

Exclusion:

* Pregnant / nursing
* Inadequate contraception
* Brain metastasis
* Primary ocular or mucosal melanoma
D: Inclusion Criteria:

* 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 assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible.
* The subject must have a radiologically measurable tumor
* The subject is able to carry out daily life activities without significant difficulty (ECOG performance status score of 0 or 1).
* Able to swallow and retain oral medication
* Sexually active subjects must use acceptable methods of contraception during the course of the study
* Adequate organ system function and blood counts

Exclusion Criteria:

* Prior treatment with a BRAF or a MEK inhibitor
* Prior systemic anti-cancer 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.)
* The subject has received major surgery or certain tyes of cancer therapy with 21 days of starting treatment
* Current use of prohibited medication listed in the protocol
* Left ventricular ejection fraction less than the lower limit of normal
* Uncontrolled blood pressurl
* History or current evidence of retinal vein occlusion or central serous retinopathy
* Brain metastases unless previously treated with surgery or stereotactic radiosurgery and the disease has been stable for at least 12 weeks
* The subject is pregnant or nursing

Answer: C