Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes

Inclusion Criteria

• •Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
• •Patients must have histologically confirmed solid tumor with a known pathogenic mutation in BRCA1/2, PALB2, RAD51C, RAD51D, ATM, BARD1, BLM, BRIP1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN (NBS1), RAD50 and RAD51B as confirmed by a Clinical Laboratory Improvement Amendments (CLIA)-certified method. Patients with alterations defined only by germline testing are eligible. Other qualifying HRD alterations may be considered if approved by the principal investigator and the Cancer Therapy Evaluation Program (CTEP) monitor
• •Any number of prior therapy regimens is allowed
• •Patients with cancers for which PARP inhibitors have been approved as standard-of-care must have received a PARP inhibitor prior to enrollment on this study. Other patients may be either PARP inhibitor-naïve (i.e., never have received a PARP inhibitor) or have disease that is PARP inhibitor-resistant (i.e., disease that has progressed radiologically based on Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 while receiving any PARP inhibitor)
• •Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of novobiocin in patients \< 18 years of age, children are excluded from this study
• •Eastern Cooperative Oncology Group Performance (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• •Absolute neutrophil count \>= 1,500/mcL
• •Leukocytes \>= 3,000/mcL
• •Platelets \>= 100,000/mcL
• •Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN)
• •Aspartate transaminase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine transferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 × institutional ULN
• •Glomerular filtration rate (GFR) \>= 60 mL/min (via the chronic kidney disease epidemiology \[CKD-EPI\] glomerular filtration rate estimation)
• •Fridericia's formula-corrected QT interval (QTcF) =\< 480 ms
• •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• •Patients should be New York Heart Association Functional Classification of class 2B or better
• •Patients must have tumors amenable to biopsies, and be willing to undergo biopsies at two time points (pre- and on-treatment)
• •The effects of novobiocin on the developing human fetus are unknown. For this reason and because polymerase theta (POLtheta) inhibitor agents have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 months after completion of novobiocin administration. Effective contraception is defined as a method that achieves a failure rate of less than 1% per year when used consistently and correctly. (Note: Because of a concern for decreased effectiveness of estrogen-containing oral agents when given with novobiocin, barrier methods and abstinence are the preferred methods for contraception). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• •Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available will also be eligible