Nab‑paclitaxel PIPAC with paclitaxel and ramucirumab for stomach cancer that has spread to the peritoneum

Inclusion Criteria:

* Patients must have failed first-line systemic therapy (fluorouracil, leucovorin calcium, oxaliplatin \[FOLFOX\] with or without immunotherapy, or other fluoropyrimidine and platinum-based therapy)

  * Prior immunotherapy allowed
  * Up to 4 cycles of second-line therapy allowed if no progression is documented
* Documented informed consent of the participant and/or legally authorized representative

  * Assent, when appropriate, will be obtained per institutional guidelines
* Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  * If unavailable, exceptions may be granted with study principal investigator (PI) approval
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed gastric adenocarcinoma
* Visible peritoneal metastatic disease on cross-sectional imaging or diagnostic laparoscopy (does not have to be measurable by RECIST 1.1)
* Fully recovered from acute toxic effects (except alopecia, hearing loss, or non-clinically significant laboratory abnormalities) ≤ grade 1 of prior anti-cancer therapy
* The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then a 24-hour urine must be collected and must demonstrate \< 1000mg protein in 24 hours
* Complete medical history and physical exam (within 28 days prior to day 1 of protocol therapy)
* Absolute neutrophil count (ANC) ≥ 1,500/mcL (within 28 days prior to day 1 of protocol therapy)
* Platelets ≥ 100,000/mcL (within 28 days prior to day 1 of protocol therapy)
* Hemoglobin ≥ 8 g/dL (within 28 days prior to day 1 of protocol therapy)
* Serum albumin ≥ 2.8 g/dL (within 28 days prior to day 1 of protocol therapy)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease, then direct bilirubin \< 1.5 mg/dL) (within 28 days prior to day 1 of protocol therapy)
* Aspartate aminotransferase (AST) ≤ 5 x ULN (within 28 days prior to day 1 of protocol therapy)
* Alanine aminotransferase (ALT) ≤ 5 x ULN (within 28 days prior to day 1 of protocol therapy)
* International normalized ratio (INR) ≤ 1.5 x ULN (within 28 days prior to day 1 of protocol therapy)
* Prothrombin time (PT) ≤ 1.5 x ULN (within 28 days prior to day 1 of protocol therapy)
* Partial thromboplastin time (PTT) ≤ 1.5 x ULN (within 28 days prior to day 1 of protocol therapy)
* Calculated creatinine clearance of ≥ 45 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 28 days prior to day 1 of protocol therapy)
* Seronegative for HIV antigen (Ag)/antibody (Ab) combo (within 28 days prior to day 1 of protocol therapy)

  * If seropositive, patient may be eligible if they are stable on antiretroviral therapy, have a CD4 T cell count ≥ 200/µL, and have an undetectable viral load
* Documented virology status of hepatitis, confirmed by hepatitis B virus (HBV) and hepatitis C virus (HCV) tests (within 28 days prior to day 1 of protocol therapy)

  * For patients with active HBV, HBV deoxyribonucleic acid (DNA) \< 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to day 1 of cycle 1, and willingness to continue anti-HBV treatment during the study (per standard of care)
  * If seropositive for HCV, nucleic acid quantification must be performed. Viral load must be undetectable
* WOMEN OF CHILDBEARING POTENTIAL (WOCBP): Negative urine or serum pregnancy test (within 28 days prior to day 1 of protocol therapy)

  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential to use an effective method of birth control (e.g., licensed hormonal/barrier methods or surgery intended to prevent pregnancy \[or with a side effect of pregnancy prevention\]) or abstain from heterosexual activity for the course of the study through at least 14 months after the last dose of protocol therapy.

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* Intolerance to taxanes
* Bowel obstruction requiring exclusive total parenteral nutrition
* Any history of, or current, brain or subdural metastases
* Life expectancy \< 3 months
* Treatment with therapeutic oral or IV antibiotics within 14 days prior to day 1 cycle 1 of treatment

  * Patients receiving prophylactic antibiotics are eligible, provided the signs of active infection have resolved
* Any prior malignancy except adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for two years
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents (taxanes, etc.)
* Clinically significant uncontrolled illness such as uncontrolled hypertension (HTN)
* History of arterial thromboembolic events such as myocardial infarction (MI), cerebrovascular accident (CVA)
* History of gastrointestinal (GI) perforation
* FEMALES ONLY: Pregnant or breastfeeding
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)