Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery

All prior treatment-related toxicities resolved to =\< grade 1 or are determined to be clinically stable by the investigator

Has completed prior therapies according to the criteria below:

* Cytotoxic chemotherapy - at least 21 days since last dose prior to first dose of ribociclib

* Small molecule inhibitors - at least 14 days since last dose prior to first dose of ribociclib

* Monoclonal antibodies - at least 3 half-lives since last dose prior to first dose of ribociclib; exception: denosumab for bony metastases is allowable

* Immunotherapy (e.g. tumor vaccines) - at least 42 days since last dose prior to first dose of ribociclib

* Radiation - at least 14 days since last dose prior to first dose of ribociclib

Able to swallow capsules

Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

Life expectancy \> 3 months

Ability to understand and the willingness to sign a written informed consent document; subject has signed the informed consent (ICF) prior to any screening procedures being performed and is able to comply with protocol requirements

Subjects with low grade tumors (histologic grade 1/3)

Histologic diagnosis for which single-agent doxorubicin is NOT appropriate therapy, including but not limited to:

* Alveolar or embryonal rhabdomyosarcoma

* Ewings sarcoma or primitive neuroectodermal tumor (PNET)

* Osteosarcoma

* Gastrointestinal stromal tumor (GIST)

Prior systemic therapy with an anthracycline for any indication

Known hypersensitivity to any of the excipients of ribociclib or doxorubicin (including to peanut and soy)

Currently receiving any of the following that cannot be discontinued at least 7 days prior to starting study drug:

* Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges

* Medications with a narrow therapeutic window that are predominantly metabolized through CYP3A4/5

* Herbal supplements, such as St. John's wort; the use of marijuana or its derivatives is allowed in States with statutes permitting the use of recreational or medical marijuana

Uncontrolled intercurrent medical condition including, but not limited to:

* Uncontrolled infection

* Symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III-IV)

* Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening

* Uncontrolled cardiac arrhythmia or arrhythmia requiring medication other than beta blocker

* Psychiatric illness/social situations that would limit compliance with study requirements

* Any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, etc.)

Concurrent malignancy or malignancy within 3 years prior to starting study drug, except:

* Malignancies that have completed therapy and are considered by their physician to be at less than 30% risk of relapse, or

* Malignancies not requiring treatment (e.g., RAI stage 0 chronic lymphocytic leukemia \[CLL\])

Central nervous system (CNS) involvement unless they meet ALL of the following criteria:

* At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment

* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases

Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea/vomiting/diarrhea, malabsorption syndrome, or major small bowel resection)

Known history of human immunodeficiency virus (HIV) infection (testing not mandatory); NOTE: HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ribociclib; in addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated

Systolic blood pressure (SBP) \> 160 mmHg or \< 90 mmHg at screening; if initial screening SBP is outside of the eligible range, blood pressure may be re-checked after intervention; SBP must be documented as stable and within the eligible range prior to starting study drug

Currently receiving rivaroxaban, apixaban, endoxaban, warfarin or other warfarin derived anticoagulant; therapy with heparin, low molecular weight heparin (LMWH), dabigatran or fondaparinux is allowed; if transitioning from a prohibited anticoagulant, a minimum washout of 7 days from last dose of the prohibited medication is required prior to ribociclib start

Participation in a prior investigational interventional study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer

Major surgery within 14 days prior to starting study drug or has not recovered from surgical complications (tumor biopsy is not considered as major surgery)

History of congenital long QT syndrome or torsades de pointes

History of non-compliance to medical regimen or inability to grant consent

Pregnant or nursing (lactating) women; breastfeeding should be discontinued

What this study is about