Onalespib, Dabrafenib, and Trametinib in Treating Patients With BRAF-Mutant Melanoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery

Patients who received prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to day 1 of cycle 1; patients are permitted to be on dabrafenib and trametinib standard of care at start of therapy without wash-out period prior to day 1 of cycle 1; dosing will change to protocol determined dose levels on day 1 of cycle 1

Patients must not have received prior HSP90 inhibitor therapy

Patients who are receiving any other investigational agents; patients who have taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to randomization

Patients with history of activating RAS mutation positive tumors regardless of interval from current study; however, patients may have concurrent BRAFV600 and RAS mutations in the tumor to be treated with protocol therapy

Patients must have no clinical evidence of leptomeningeal or brain metastasis causing spinal cord compression that are symptomatic or untreated or not stable for \>= 4 weeks (must be documented by imaging) or requiring corticosteroids; subjects on a stable dose of corticosteroids \> 1 month or who have been off of corticosteroids for at least 2 weeks can be enrolled with approval of the Cancer Therapy Evaluation Program (CTEP) medical monitor; subjects must also be off of enzyme-inducing anticonvulsants for \> 4 weeks

History of known immediate or delayed hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to AT13387, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO)

Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements

Pregnant women are excluded from this study; breastfeeding should be discontinued prior to the mother being treated with the study drugs

Patients known to be human immunodeficiency virus (HIV)-positive patients and on combination antiretroviral therapy are ineligible

History of another malignancy other than the study indication under this trial within 5 years of study enrollment; does not apply to subjects who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, in situ breast cancer, or other in situ cancers

History of interstitial lung disease or pneumonitis

History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):

* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)

* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure \> 21 mm mercury (Hg)

History or evidence of cardiovascular risk including any of the following:

* An average of the three most recent QT intervals corrected for heart rate using the Bazett's formula QTcB \>= 460 msec

* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to randomization are eligible)

* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization

* History or evidence of current \>= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system

* Treatment-refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy

* Abnormal cardiac valve morphology (\>= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities \[i.e., mild regurgitation/stenosis\] can be entered on study); subjects with moderate valvular thickening should not be entered on study

* Prior placement of an implantable defibrillator

* History of or identification on screening imaging of intracardiac metastases

No known active infection with hepatitis B virus (HBV), or hepatitis C virus (HCV); patients with chronic or cleared HBV infection and HCV infection are eligible

Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:

* Other anti-cancer therapy while on study treatment; (note: megestrol \[Megace\] if used as an appetite stimulant is allowed)

* Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis

* The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], ginkgo biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)

* Current use of a prohibited medication; patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded

What this study is about