A Study Combining the Peposertib (M3814) Pill With Standard Chemotherapy in Patients With Ovarian Cancer With an Expansion in High Grade Serous Ovarian Cancer and Low Grade Serous Ovarian Cancer

DOSE ESCALATION PHASE: Women with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancer are eligible. This includes, but is not limited to, the following histologic types: serous adenocarcinoma (grade 1,2, or 3/ high grade or low grade), endometrioid adenocarcinoma, carcinosarcoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial adenocarcinoma, transitional cell carcinoma, or adenocarcinoma not otherwise specified

EXPANSION PHASE: The expansion phase will simultaneously accrue to 2 cohorts, low grade serous ovarian cancer (LGSOC) and high grade serous ovarian cancer (HGSOC)

* Patients accrued to the LGSOC cohort will have recurrent or persistent low grade serous ovarian cancer or grade 1 serous ovarian cancer

* Patients accrued to the HGSOC cohort will have recurrent or persistent high grade serous ovarian cancer

Patients must have measurable disease by defined Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

Prior therapy:

* Patients must have received at least one prior line of platinum-based chemotherapy

* Patients can have received an unlimited number of additional lines of chemotherapy, targeted therapy, biologic therapy, or hormonal therapy

* Any prior therapy directed at the malignant tumor, including chemotherapy, biologic/targeted therapy, immunotherapy, or hormonal therapy must be discontinued at least 4 weeks, one cycle, or 5 half-lives (whichever is shortest) prior to study treatment initiation

Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of peposertib (M3814) in combination with pegylated liposomal doxorubicin in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

Patients with platinum-sensitive ovarian cancer are eligible for only the dose expansion phase if their provider feels that PLD would be an appropriate treatment option for them. Patients with platinum-sensitive ovarian cancer should also be offered any higher priority studies for which they are potentially eligible and/or platinum based chemotherapy or a PARP inhibitor if they are eligible for such therapy

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

Patients must have a cardiac ejection fraction \>= the institutional lower limit of normal (LLN)

Hemoglobin \>= 9 g/dL

Absolute neutrophil count \>= 1,500/mcL

Platelets \>= 100,000/mcL

Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN

Alkaline phosphatase =\< 2.5 x institutional ULN

Creatinine clearance \> 30 ml/min

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

Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

* The effects of peposertib (M3814) and liposomal doxorubicin on the developing human fetus are unknown and there is the potential for teratogenic or abortifacient effects. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study treatment, and for 6 months after completion of peposertib (M3814) administration. 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. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with peposertib (M3814), breastfeeding should be discontinued if the mother is treated with peposertib (M3814)

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 with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Archival formalin-fixed paraffin-embedded (FFPE) tissue collected within the past 36 months prior to registration must be available for submission for deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) analysis

What this study is about