Olaparib and Ramucirumab in Treating Patients With Metastatic or Locally Recurrent Gastric or Gastroesophageal Junction Cancer That Cannot Be Removed by Surgery

The patient has metastatic disease or locally recurrent, unresectable disease

The patient must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

The patient must have experienced disease progression during or within 4 months after the last dose of chemotherapy for metastatic disease, during or within 6 months after the last dose of adjuvant chemotherapy, or have been intolerant of previous chemotherapy

The patient must have experienced disease progression or intolerance as outlined above after treatment with 1 or more prior chemotherapies

All previous treatments are acceptable as long as they did not contain bevacizumab, ramucirumab or PARP inhibitors

Elevation in tumor markers without radiographic evidence of disease progression is not satisfactory for progression on previous treatment

The patient is \>= 18 years of age

The patient has a life expectancy of \>= 16 weeks

Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (Karnofsky \>= 60%)

Hemoglobin \>= 10 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days (within 28 days prior to administration of study treatment)

White blood cells (WBC) \> 3 x 10\^9/L (within 28 days prior to administration of study treatment)

Absolute neutrophil count (ANC) \>= 1.5 10\^9/L (within 28 days prior to administration of study treatment)

Platelet count \>= 100 X 10\^9/L (within 28 days prior to administration of study treatment)

No features suggestive of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated (within 28 days prior to administration of study treatment)

Total bilirubin =\< 1.5 x the institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)

Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN unless liver metastases are present in which case they must be =\< 5 x ULN (within 28 days prior to administration of study treatment)

Calculated serum creatinine clearance \>= 60 mL/min/1.73 m\^2 (within 28 days prior to administration of study treatment)

Proteinuria with urinary protein =\< 1+ on dipstick or routine urinalysis, or a 24-hour urine collection for protein \< 1000 mg of protein in 24 hours (within 28 days prior to administration of study treatment)

Coagulation parameters (international normalized ratio \[INR\], activated partial thromboplastin time \[aPTT\]) =\< 1.25 x institutional limits, except where a lupus anti-coagulant has been confirmed or the patient is on warfarin; patients on full dose anticoagulation must be on a stable dose for at least 14 days; if receiving warfarin, the patient must have an INR =\< 3.0 without any evidence of active bleeding within 14 days prior to first dose of study treatment or a pathologic condition that carries a high risk of bleeding (tumor involvement with major blood vessels or varices) (within 28 days prior to administration of study treatment)

Postmenopausal or evidence of non-childbearing status for women of childbearing potential a negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1; postmenopausal is defined as:

* Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments

* Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50

* Radiation-induced oophorectomy with last menses \> 1 year ago

* Chemotherapy-induced menopause with \> 1 year interval since last menses

* Surgical sterilization (bilateral oophorectomy or hysterectomy)

The effects of olaparib and ramucirumab on the developing fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception including hormonal, barrier, or abstinence; contraception must be started prior to study enrollment; female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to treatment; 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; both men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study participation, and for 3 months after completion of olaparib and ramucirumab administration; male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner

Ability to understand and the willingness to sign a written informed consent document

The patient must be willing to undergo a biopsy prior to treatment, an on treatment biopsy at week 16 is optional if felt to be safe in the opinion of the investigator

For inclusion into optional exploratory genetic and biomarker research, patients must fulfill the following criteria:

* Provision of informed consent for genetic research

* Provision of informed consent for biomarker research

* If a patient declines to participate in the optional exploratory genetic research or the optional biomarker research, there will be no penalty or loss of benefit to the patient; the patient will not be excluded from other parts of the study

Patients must be able to tolerate oral medications by mouth, and not have a gastrointestinal illness that would preclude absorption of olaparib

Adequately controlled blood pressure (BP) \< 140 mmHg (systolic) and \< 90 mmHg (diastolic) taken in the clinic setting by a medical professional within 2 weeks prior to starting study; patients with hypertension may be managed with up to a maximum of 3 antihypertensive medications; a cardiologist or blood pressure specialist must evaluate patients who are on 3 antihypertensive medications within 4 weeks of enrollment

Patients who have the following risk factors are considered to be at increased risk for cardiac toxicity and must have documented left ventricular ejection fraction (LVEF) by echocardiogram greater than institution's lower limit of normal (or 55% if threshold for normal not otherwise specified by institutional guidelines) obtained within 3 months

* Prior treatment with anthracyclines

* Prior treatment with trastuzumab

* A New York Heart Association (NYHA) classification of II controlled with treatment

* Prior central thoracic radiation therapy (RT), including RT to the heart

* History of myocardial infarction within 12 months (patients with history of myocardial infarction within 6 months are excluded)

History of hypertensive crisis or hypertensive encephalopathy within 3 years

Major surgery within 28 days of starting study treatment and patients must have recovered from any effects of any major surgery

An open biopsy, non-healing wound, ulcer or significant traumatic injury within 28 days prior to starting treatment (percutaneous, endobronchial, and endoscopic biopsies are allowed)

The patient has received chemotherapy, radiotherapy (except for palliative reasons), immunotherapy, or targeted therapy for gastric cancer within 3 weeks of study treatment

The patient has received any investigational therapy within 4 weeks of enrollment

The patient has received prior therapy with bevacizumab, ramucirumab or any PARP inhibitor, including olaparib

Patients must not have evidence of coagulopathy or bleeding diathesis; therapeutic anticoagulation for prior thromboembolic events is permitted; the clinical indication for therapeutic anticoagulation must be clearly documented prior to enrollment and must be discussed with the principal investigator (PI); due to risk of serious bleeding with ramucirumab, patients on greater than or equal to 2 anti-thrombotic agents, including but not limited to anti-platelet agents (nonsteroidal anti-inflammatory drugs \[NSAIDS\]/aspirin, clopidogrel), heparin, low molecular weight heparin, warfarin and a direct thrombin inhibitor will be excluded

The patient has elective or planned major surgery to be performed during the course of the clinical trial

History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib and ramucirumab

Patients with a known hypersensitivity to olaparib or any of the excipients of the product

Patients with a known hypersensitivity to the combination/comparator agent

Pregnant or breast feeding women are excluded from this study because olaparib and ramucirumab have the potential for teratogenic or abortifacient effects

Immunocompromised patients, this includes human immunodeficiency virus (HIV)-positive patients, because of the potential for interaction with antiretroviral therapy and ramucirumab and/or olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy

Patients with a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (defined as detectable hepatitis C virus \[HCV\] ribonucleic acid \[RNA\]) infection; Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority

The patient has known and active alcohol or drug dependency

The patient has a concurrent active malignancy other than treated non-melanoma skin cancers or in situ neoplasm; a patient with a prior history of malignancy is eligible, provided that they have been free of disease for \>= 5 years

Patients may not have features suggestive of myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) on peripheral blood smear or bone marrow biopsy, if clinically indicated

Patients may not have had a prior allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)

Patients may not have current signs and/or symptoms of bowel obstruction within 1 month prior to starting study drugs, except if it was a temporary incident (improved within \< 24 hours \[hr\] with medical management)

History of hemoptysis within the last 1 month

History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the last 3 months

Dependency on IV hydration \> 1 day per week within the screening period

Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4/5 are ineligible; the required washout period prior to starting treatment is 2 weeks for CYP3A inhibitors, 3 weeks for CYP3A inducers, and 5 weeks for enzalutamide; dihydropyridine calcium-channel blockers are permitted for management of hypertension

Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Previous enrollment in the present study

Current use of natural herb products or other complementary alternative medications; if used previously, patients must have at least 1-week washout and must stop using them while participating in this study

What this study is about