Testing the Addition of Ipatasertib to the Usual Chemotherapy Treatment (Paclitaxel and Carboplatin) for Stage III or IV Epithelial Ovarian Cancer

This phase I/IB trial tests the safety, side effects, and best dose of ipatasertib in combination with paclitaxel and carboplatin in treating patients with stage III or IV epithelial ovarian cancer. Ipatasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Paclitaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Giving ipatasertib in combination with paclitaxel and carboplatin may lower the chance of the tumor growing or spreading for longer than the paclitaxel and carboplatin alone.

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) and the dose limiting toxicities (DLTs) of ipatasertib in combination with paclitaxel and carboplatin as neoadjuvant chemotherapy for ovarian cancer.

II. To determine the feasibility of the treatment regimen once the MTD is estimated.

III. To assess the toxicities of ipatasertib in combination with paclitaxel and carboplatin by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

SECONDARY OBJECTIVE:

I. Objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 prior to interval debulking surgery (IDS).

TRANSLATIONAL RESEARCH OBJECTIVES:

I. To evaluate the change of phosphorylated (p)PRAS40 expression in the pre-treatment tumor versus (vs.) on-treatment tumor.

II. To identify the pharmacokinetics of ipatasertib in the tissue and blood. III. To correlate antitumor response with genomic alterations in PI3K pathway genes (PTEN, PIK3CA, PIK3R1, AKT1, p53 loss, KRAS, NF1, TSC1/TSC1).

IV. To correlate antitumor response with transcriptomic alterations in PI3K pathway genes (PTEN, PIK3CA, PIK3R1, AKT1, p53 loss, KRAS, NF1, TSC1/TSC1).

V. To correlate response with PTEN loss.

OUTLINE: This is a dose-escalation study of ipatasertib followed by a dose-expansion study.

Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive ipatasertib orally (PO) once daily (QD) until 24 hours before surgery in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 and 90 days.

Eligibility Criteria:
Inclusion Criteria:

* Pathologically proven diagnosis of ovarian cancer (ovarian cancer = fallopian tube cancer, ovarian cancer, primary peritoneal cancer). Required data element: submission of pathology report. Patients with the following histologic cell types are eligible:

  * High grade serous
  * Endometrioid adenocarcinoma, grade 3 Genomic/genetic testing results will be a data collection element if performed as part of usual care (germline genetic testing, tumor genomic testing, homologous recombination deficiency \[HRD\] testing). Genetic/genomic testing results should be uploaded if they become available anytime during conduct of the study
* Appropriate stage for study entry defined as stage III or stage IV based on the following diagnostic workup:

  * History/physical examination within 14 days prior to registration
  * Imaging with computed tomography (CT) chest/abdomen/pelvis (C/A/P) within 28 days prior to registration
* Patients must have evaluable disease or measurable disease defined by RECIST version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>= 10 mm when measured by CT or magnetic resonance imaging (MRI). Lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
* Pre-treatment formalin-fixed, paraffin-embedded (FFPE) tumor block collected from laparoscopy (preferred) or five 18G cores by radiology/interventional radiology (acceptable) must be available for submission
* Disease must be considered unresectable via primary debulking surgery and in need of neoadjuvant chemotherapy (NACT) prior to debulking surgery. This assessment of unresectability can be made via imaging or laparoscopic scoring
* No prior therapy directed at ovarian cancer
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 within 14 days prior to registration
* Absolute neutrophil count \>= 1,000/mcl (within 14 days prior to registration)
* Platelets \>= 100,000/mcl (within 14 days prior to registration)
* Creatinine =\< institutional/laboratory upper limit of normal (ULN) or creatinine clearance (CrCL) or estimated glomerular filtration rate (eGFR) of \>= 60 mL/min estimated using either the Cockcroft-Gault equation, the Modification of Diet in Renal Disease Study, or as reported in the comprehensive metabolic panel/basic metabolic panel (eGFR) (within 14 days prior to registration)
* Total bilirubin =\< 1.5 x ULN (patients with known Gilbert's disease who have bilirubin level =\< 3 x ULN may be enrolled) (within 14 days prior to registration)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x ULN (within 14 days prior to registration)
* 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
* Women of childbearing potential (WOCBP) must agree to use two forms of birth control (hormonal or barrier method of birth control; abstinence) agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 28 days after the last dose of ipatasertib and agreement to refrain from donating eggs during this same period
* 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
* 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 history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
* Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

* Prior treatment with agent(s) targeting PI3K/AKT/mTor pathway
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib, paclitaxel or carboplatin
* Currently receiving any other investigational agents or has received an investigational agent within 4 weeks of study registration
* Abnormal gastrointestinal function. This includes gastrointestinal (GI) obstruction or bleeding or signs/symptoms thereof within 3 months of study registration
* Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula
* Received prior radiotherapy to any portion of the abdominal cavity or pelvis
* Patients with uncontrolled intercurrent illness
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Patients with active infections requiring intravenous antibiotics
* Patients with diabetes either requiring insulin therapy or with a baseline fasting glucose \>= 160 mg/dL and/or high glycosylated hemoglobin (HbA1c) (\> 8), suggesting poorly controlled diabetes. Fasting is defined as abstaining from food and drink (with the exception of water) for at least 8 hours
* Patients with grade \>= 2 uncontrolled or untreated hypercholesterolemia (\> 300 mg/dL) or hypertriglyceridemia (\> 300 mg/dL) would be an ineligible
* History of or active inflammatory bowel disease (e.g., Crohn's disease and/or ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
* Lung disease: Pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
* Patients with known brain metastases or leptomeningeal disease are not eligible, as prior treatment directed at ovarian cancer is not allowed
* Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to registration

  * Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Known clinically significant history of liver disease consistent with Child Pugh class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
* Pregnant women are excluded from this study because ipatasertib is an oral AKT inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ipatasertib, breastfeeding should be discontinued if the mother is treated with ipatasertib. These potential risks may also apply to other agents used in this study